NCBI Conserved Domain Search

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 147.21 E-value: 2.16e-42

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLCGG 154
Cdd:cd01803     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 76

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 145.66 E-value: 7.08e-42

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLRGG 78
Cdd:cd01803     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 76

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 137.23 E-value: 5.87e-37

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLCG 153
Cdd:COG5272     1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRTLG 75

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 120.63 E-value: 7.20e-33

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRLR 625
Cdd:cd01803     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLR 74

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 125.29 E-value: 9.93e-33

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLRG 77
Cdd:COG5272     1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRTLG 75

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 110.61 E-value: 3.26e-29

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIqpQPNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd01803     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGI--PPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVL 71

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 109.46 E-value: 8.35e-29

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLFFHIRHG 468
Cdd:cd01803     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 76

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 111.42 E-value: 7.83e-28

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:COG5272     1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHL 69

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 111.42 E-value: 8.38e-28

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:COG5272     1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTR 72

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 105.60 E-value: 1.67e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVSTFSGKnftsdTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRL 234
Cdd:cd01803     1 MQIFVKTLTGK-----TITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQL--EDGRTLSDYNIQKESTLHLVLRL 73


                  ...
gi 1063710493 235 RGD 237
Cdd:cd01803    74 RGG 76

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 110.26 E-value: 1.75e-27

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIqpQPNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:COG5272     1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGI--PPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVT 71

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 105.22 E-value: 2.40e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 469 MQIFVKTFsfsgetpTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIHQLFLQ 548
Cdd:cd01803     1 MQIFVKTL-------TGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRL 73


                  ...
gi 1063710493 549 RGG 551
Cdd:cd01803    74 RGG 76

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

Pssm-ID: 340501 [Multi-domain] Cd Length: 76 Bit Score: 104.45 E-value: 4.41e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFRC 317
Cdd:cd01803     1 MQIFVKTL-----TGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRG 75


                  .
gi 1063710493 318 G 318
Cdd:cd01803    76 G 76

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 108.72 E-value: 7.01e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVSTFSGKnftsdTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRL 234
Cdd:COG5272     1 MQIFVKTLTGK-----TITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQL--EDDRTLADYNIQKESTLHLVTRT 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063710493 235 RGDMYIFVKN----LPYNSFTGENFILEVESSDTIDNVKA 270
Cdd:COG5272    74 LGISEIELSNlkldLDPNPSHLFIFILGLIGSYSYTIGSI 113

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 103.49 E-value: 9.61e-27

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493   79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 100.32 E-value: 1.17e-25

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  81 IFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLC 152
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 104.87 E-value: 1.32e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 469 MQIFVKTfsfsgetPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH----- 543
Cdd:COG5272     1 MQIFVKT-------LTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHlvtrt 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 544 ----QLFLQRGGMQIFIKTLTGK-TIILEVESSDTIANVKEKIQVKEGIKPDQQ-------------MLIFFGQQLEDGV 605
Cdd:COG5272    74 lgisEIELSNLKLDLDPNPSHLFiFILGLIGSYSYTIGSINGTVQKSGQIRDQLkiniqnlrtglyiLKLDKGNQLGFIK 153


                  ....*.
gi 1063710493 606 TLGDYD 611
Cdd:COG5272   154 EAQIYG 159

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 98.23 E-value: 7.24e-25

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493   5 IYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLRGG 78
Cdd:cd01806     1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 97.84 E-value: 9.98e-25

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  81 IFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLCGG 154
Cdd:cd01806     1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 97.33 E-value: 1.32e-24

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493    3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444084 [Multi-domain] Cd Length: 213 Bit Score: 101.40 E-value: 2.30e-24

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTR 314
Cdd:COG5272     1 MQIFVKTL-----TGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTR 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 90.31 E-value: 3.56e-22

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493   5 IYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLR 76
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 89.63 E-value: 7.30e-22

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 89.15 E-value: 8.72e-22

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 554 IFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRLR 625
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 86.07 E-value: 1.27e-20

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 395 IFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLFFHIR 466
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 85.34 E-value: 1.82e-20

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493  81 IFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLV 148
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 85.46 E-value: 2.16e-20

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRL 151
Cdd:cd01802     1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLAM 73

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 82.82 E-value: 1.76e-19

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 554 IFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRLR 625
Cdd:cd01806     1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALR 72

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 82.50 E-value: 2.35e-19

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRL 151
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRL 73

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 82.31 E-value: 2.35e-19

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqpNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPP--EQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVL 71

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 82.22 E-value: 2.45e-19

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 240 IFVKNLPYNSFTgenfiLEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFR 316
Cdd:pfam00240   1 ITVKTLDGKKIT-----LEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 82.31 E-value: 2.59e-19

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493  238 MYIFVKNLPYNSFTgenfiLEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTR 314
Cdd:smart00213   1 IELTVKTLDGKTIT-----LEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 81.92 E-value: 2.94e-19

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493  393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHL 69

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 81.22 E-value: 7.40e-19

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLR 76
Cdd:cd01802     1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLAMR 74

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 81.03 E-value: 7.64e-19

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLRGG 78
Cdd:PTZ00044    1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRGG 76

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 81.03 E-value: 9.01e-19

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLCGG 154
Cdd:PTZ00044    1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRGG 76

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 80.33 E-value: 1.19e-18

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493   5 IYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLV 72
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 79.56 E-value: 2.20e-18

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 395 IFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLF 462
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 78.91 E-value: 3.92e-18

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRLR 625
Cdd:cd01802     1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLAMR 74

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 78.37 E-value: 5.43e-18

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 157 IFVSTFSGKNFTsdtltLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRLR 235
Cdd:pfam00240   1 ITVKTLDGKKIT-----LEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVL--EDDQTLGEYGIEDGSTIHLVLRQR 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 77.98 E-value: 8.02e-18

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 471 IFVKTFSfsgetptCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIHQLFLQR 549
Cdd:pfam00240   1 ITVKTLD-------GKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 77.88 E-value: 1.11e-17

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLR 76
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRLR 74

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 77.25 E-value: 1.21e-17

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 554 IFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLV 621
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 76.66 E-value: 2.32e-17

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 321 IFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGCTLADYSIQKESTLHLVLGMQ 394
Cdd:cd01806     1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQ--QRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALR 72

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 76.00 E-value: 3.97e-17

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493  80 QIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLV 148
Cdd:cd16107     1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 75.37 E-value: 6.83e-17

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493  469 MQIFVKTfsfsgetPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:smart00213   1 IELTVKT-------LDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIH 68

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

Pssm-ID: 459726 [Multi-domain] Cd Length: 72 Bit Score: 74.13 E-value: 1.71e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 321 IFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqpNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPP--EQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVL 69

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 74.03 E-value: 2.07e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRLR 625
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRLR 74

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 73.71 E-value: 3.06e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRLR 625
Cdd:PTZ00044    1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLR 74

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 73.15 E-value: 3.62e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDG-RTLADYNIQKESTLHLV 148
Cdd:cd17053     1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGdKTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 72.63 E-value: 5.85e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 321 IFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqpNLQRLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPV--EQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 72.70 E-value: 5.94e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  79 MQIFVQTltGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLCGG 154
Cdd:cd01793     1 MQLFVRA--QSLHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVRLLGG 74

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 71.99 E-value: 1.03e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDG-RTLGDYNIRNESTLHLF 462
Cdd:cd17053     1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGdKTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 69.51 E-value: 7.37e-15

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILP-RQQRLIFAGKQLEDGRTLADYNIQKESTL 145
Cdd:cd01805     1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGDFPaSGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 69.85 E-value: 7.56e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:PTZ00044    1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQ--IRLIYSGKQMSDDLKLSDYKVVPGSTIHMVL 71

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 69.72 E-value: 7.60e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 482 TPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIHQLFLQRGG 551
Cdd:cd01806     5 TLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 69.79 E-value: 7.87e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLFFHIR 466
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRLR 74

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 69.31 E-value: 9.45e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd01807     1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

Pssm-ID: 214563 [Multi-domain] Cd Length: 72 Bit Score: 69.21 E-value: 9.48e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493  155 MQIFVSTFSGKNFTsdtltLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALR 233
Cdd:smart00213   1 IELTVKTLDGKTIT-----LEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVL--EDDRTLADYGIQDGSTIHLVLR 72

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 68.78 E-value: 1.46e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 486 KTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd17039     9 KTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIH 66

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 68.30 E-value: 1.79e-14

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493   4 QIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLV 72
Cdd:cd16107     1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 68.14 E-value: 2.49e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGV-TLGDYDIHKKSTLYLV 621
Cdd:cd17053     1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGDkTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 67.52 E-value: 4.45e-14

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 553 QIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLV 621
Cdd:cd16107     1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 67.09 E-value: 6.10e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFR 316
Cdd:cd01810     1 LSIFVRNE-----KGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRLR 74

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 67.00 E-value: 6.52e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd01807     1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 66.60 E-value: 8.43e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493   4 QIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGL-TLADYNIQKESTLHLV 72
Cdd:cd17053     2 TVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGDkTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 66.08 E-value: 1.13e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 240 IFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLV 312
Cdd:cd17039     1 ITVKTL-----DGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

Pssm-ID: 340584 [Multi-domain] Cd Length: 72 Bit Score: 66.32 E-value: 1.18e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQ-RLIFAGKQLEDGRTLADYNIQKESTLHLV 148
Cdd:cd17064     1 MKVIVKSLGGKGSLLRVDASETLESLKGKASKKLDDKPSEKvKLFYSGKELEDGKSLAEQNVPPNSLVHLV 71

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 65.85 E-value: 1.71e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLF 462
Cdd:cd01807     1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLV 70

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 65.55 E-value: 1.91e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVstfsgKNFTSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRL 234
Cdd:cd01810     1 LSIFV-----RNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPL--EDQLPLGEYGLKPQSTIHMNLRL 73


                  .
gi 1063710493 235 R 235
Cdd:cd01810    74 R 74

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 65.49 E-value: 1.94e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 395 IFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLFFHIRHG 468
Cdd:cd01806     1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 65.38 E-value: 2.32e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  16 TLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRLRGG 78
Cdd:cd01793    12 TLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVRLLGG 74

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 65.43 E-value: 2.39e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVSTFSGKNFTsdtltLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRL 234
Cdd:cd01802     1 MELFIETLTGTAFE-----LRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGREL--EDDYCLHDYNITDGSTLKLVLAM 73


                  .
gi 1063710493 235 R 235
Cdd:cd01802    74 R 74

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340559 [Multi-domain] Cd Length: 68 Bit Score: 64.93 E-value: 2.55e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 157 IFVSTFSGKnftsdTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTL 228
Cdd:cd17039     1 ITVKTLDGK-----TYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKEL--KDDKTLSDYGIKDGSTI 65

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 65.27 E-value: 2.65e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493   1 MTIQIyaKTLTEKTITLDVETSDSIHNVKAKIQNKEG-IPLDQQRLIFAGKQLEDGLTLADYNIQKESTL 69
Cdd:cd01805     1 MKITF--KTLQQQTFEIEVEPSDTVLELKEKIEQEQGdFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 65.04 E-value: 2.82e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGCTLADYSIQKESTLHLVLGM 393
Cdd:cd01802     1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQ--QHLIWSGRELEDDYCLHDYNITDGSTLKLVLAM 73

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 65.00 E-value: 3.21e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 552 MQIFIKTltGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRL 624
Cdd:cd01793     1 MQLFVRA--QSLHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVRL 71

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 64.89 E-value: 3.22e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKP-DQQMLIFFGQQLEDGVTLGDYDIHKKSTL 618
Cdd:cd01805     1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGDFPaSGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

Pssm-ID: 340504 [Multi-domain] Cd Length: 74 Bit Score: 64.33 E-value: 6.25e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 240 IFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFRCG 318
Cdd:cd01806     1 IKVKTL-----TGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 63.43 E-value: 9.68e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLV 148
Cdd:cd16106     1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLV 70

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 62.77 E-value: 2.13e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQpnLQRLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd01807     1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVS--QQRLVFKGKTLADEHSLSDYSIGPGSKIHLV 70

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 61.96 E-value: 4.08e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLFFHIR 466
Cdd:cd01802     1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLAMR 74

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 61.89 E-value: 4.36e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLV 72
Cdd:cd16106     1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLV 70

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 61.54 E-value: 5.48e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 392 GMQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLF 462
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLS 71

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 61.18 E-value: 6.47e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493  81 IFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLV 148
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 61.16 E-value: 6.61e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 554 IFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVlRLRQRR 628
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAV-QGPKRK 74

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 60.98 E-value: 6.65e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 470 QIFVKTFSfsgetptCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd16107     1 QIFVRTYC-------GKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLF 67

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 60.98 E-value: 8.66e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 394 QIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd16107     1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFL 68

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 60.77 E-value: 1.08e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493   5 IYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQG 70

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 60.35 E-value: 1.21e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 482 TPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd16106     7 CSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVH 68

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 60.27 E-value: 1.31e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQ-RLIFAGKQLEDGRTLADYNIQKESTLHLVL 149
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 60.37 E-value: 1.50e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 393 MQIFVKlfGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLF 462
Cdd:cd01793     1 MQLFVR--AQSLHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVA 68

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 60.07 E-value: 1.57e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd01807     1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 59.99 E-value: 1.82e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493  87 TGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQK 141
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPK 61

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 59.67 E-value: 2.02e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIqpQPNLQRLIFLGKELKDGC-TLADYSIQKESTLHLV 390
Cdd:cd17053     1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGV--PPNEQILVYNGKRLEDGDkTLGEYGIKTGDTLYLL 71

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 59.07 E-value: 3.68e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 469 MQIFVKTFsfsgetpTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIHQLFLQ 548
Cdd:PTZ00044    1 MQILIKTL-------TGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQL 73


                  ...
gi 1063710493 549 RGG 551
Cdd:PTZ00044   74 RGG 76

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 58.49 E-value: 6.17e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 481 ETPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd01802     6 ETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLK 68

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 58.10 E-value: 7.08e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493   5 IYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLV 72
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 58.03 E-value: 8.56e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLV 621
Cdd:cd16106     1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLV 70

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 57.89 E-value: 1.08e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 320 QIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIqPQPNlQRLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd16107     1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGI-PSLE-QRLIFGGRQLQHSQSLESCKMENDATLFLV 69

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 57.68 E-value: 1.14e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVStfsGKNftsdTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRL 234
Cdd:cd01793     1 MQLFVR---AQS----LHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPL--EDDVVLGQCGIPDLATLEVAVRL 71


                  ..
gi 1063710493 235 RG 236
Cdd:cd01793    72 LG 73

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 57.74 E-value: 1.21e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 483 PTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGG-RVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd17053     8 LTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGkRLEDGDKTLGEYGIKTGDTLY 69

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 57.26 E-value: 1.89e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGCTLADYSIQKESTLHLVLG 392
Cdd:cd16106     1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQ--QRLIYKGKILKDEETLSSYKIQDGHTVHLVKG 72

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

Pssm-ID: 340500 [Multi-domain] Cd Length: 74 Bit Score: 56.95 E-value: 1.92e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFR 316
Cdd:cd01802     1 MELFIETL-----TGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLAMR 74

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 56.53 E-value: 2.92e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 551 GMQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVL 622
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 56.54 E-value: 2.98e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493  81 IFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQG 70

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 56.14 E-value: 3.39e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493  11 TEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQK 65
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPK 61

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 56.03 E-value: 4.93e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqPNLQRLIFLGKELKDGCTLADYSIQKESTL 387
Cdd:cd01805     1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGDFP-ASGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 55.82 E-value: 5.07e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 251 TGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLE-GGRTLAHYNIQKGSTLYLV 312
Cdd:cd17053     9 TGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEdGDKTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340573 Cd Length: 71 Bit Score: 55.43 E-value: 6.23e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 160 STFSGKNFTSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELfTEDNRTLADYGIRNRSTLCLA 231
Cdd:cd17053     1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRL-EDGDKTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 55.76 E-value: 6.32e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  78 GMQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVL 149
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 55.54 E-value: 6.71e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 469 MQIFVKtfSFSGETPTcktitLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd01810     1 LSIFVR--NEKGQSHT-----YEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIH 68

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 55.66 E-value: 8.97e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 402 GKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQ-LQDGRTLGDYNIRNESTLHL 461
Cdd:cd01800    21 GQVLELTLPLTDTISVLKEKIHEELGMPANKQKLQVEGGGfLKDSNSLAFYNLGSGTVLTL 81

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 54.95 E-value: 1.02e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd16106     1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHL 69

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 54.66 E-value: 1.14e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQkESTLHLVLR 150
Cdd:cd01809     1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVD-GKVIHLVER 71

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

Pssm-ID: 340584 [Multi-domain] Cd Length: 72 Bit Score: 54.76 E-value: 1.23e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEG-IPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLV 72
Cdd:cd17064     1 MKVIVKSLGGKGSLLRVDASETLESLKGKASKKLDdKPSEKVKLFYSGKELEDGKSLAEQNVPPNSLVHLV 71

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 54.49 E-value: 1.71e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVG-SPPDQQILLFRGGQLQDGRTLGDYNIRNESTL 459
Cdd:cd01805     1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGdFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

Pssm-ID: 340490 Cd Length: 75 Bit Score: 54.47 E-value: 1.90e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIF--AGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd01792     1 WDLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQQRLAVqpSGVELQDGVRLASQGLGPSSTVLLVVK 74

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 53.89 E-value: 2.22e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQkESTLHLVLR 74
Cdd:cd01809     1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVD-GKVIHLVER 71

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

Pssm-ID: 340584 [Multi-domain] Cd Length: 72 Bit Score: 53.61 E-value: 3.40e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPNLqRLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd17064     1 MKVIVKSLGGKGSLLRVDASETLESLKGKASKKLDDKPSEKV-KLFYSGKELEDGKSLAEQNVPPNSLVHLV 71

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 53.33 E-value: 3.54e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQM-LIFFGQQLEDGVTLGDYDIHKKSTLYLVL 622
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQVrLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 53.29 E-value: 4.73e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVSTFSGKNftsdtLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALRL 234
Cdd:PTZ00044    1 MQILIKTLTGKK-----QSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQM--SDDLKLSDYKVVPGSTIHMVLQL 73


                  ..
gi 1063710493 235 RG 236
Cdd:PTZ00044   74 RG 75

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 53.29 E-value: 4.77e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLFFHIRHG 468
Cdd:PTZ00044    1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRGG 76

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 52.94 E-value: 5.05e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 469 MQIFVKTFsfsgetpTCKTITLEVESSDTIDNVKVKIQHKVG-IPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTI 542
Cdd:cd01805     1 MKITFKTL-------QQQTFEIEVEPSDTVLELKEKIEQEQGdFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 52.89 E-value: 6.05e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 156 QIFVSTFSGKnftsdTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCL 230
Cdd:cd16107     1 QIFVRTYCGK-----TIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQL--QHSQSLESCKMENDATLFL 68

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2, also termed Np95/ICBP90-like RING finger protein (NIRF), or Np95-likeRING finger protein, or nuclear protein 97, or nuclear zinc finger protein Np97, or RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131(ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340643 Cd Length: 74 Bit Score: 52.95 E-value: 6.06e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  79 MQIFVQTLTGK-TITLE-VKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd17123     1 MWIQVRTIDGTeTQTIDdLSRLTKIESLREKIQELFNVRPERQRLFYRGKQLEDGHTLFDYNVGLNDIVQLLIR 74

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 52.35 E-value: 9.18e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKsTLYLVLR 623
Cdd:cd01809     1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVDGK-VIHLVER 71

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 52.37 E-value: 9.40e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTR 314
Cdd:cd01807     1 MLITVKIL-----QGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

ubiquitin; Provisional

Pssm-ID: 185411 [Multi-domain] Cd Length: 76 Bit Score: 52.52 E-value: 9.93e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFRC 317
Cdd:PTZ00044    1 MQILIKTL-----TGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRG 75


                  .
gi 1063710493 318 G 318
Cdd:PTZ00044   76 G 76

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 57.60 E-value: 1.09e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKI---QNKEGIPLDQQRLIFAGKQLEDGLTLADYNI 63
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIeaeQGKDAYPVAQQKLIYSGKILSDDKTVKEYKI 64

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 51.89 E-value: 1.45e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  13 KTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLRL 75
Cdd:cd17052    10 DLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLKV 72

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 51.81 E-value: 1.61e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  86 LTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRL-IFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd01800    19 LNGQVLELTLPLTDTISVLKEKIHEELGMPANKQKLqVEGGGFLKDSNSLAFYNLGSGTVLTLSLK 84

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

Pssm-ID: 340584 [Multi-domain] Cd Length: 72 Bit Score: 51.29 E-value: 2.10e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQI-LLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd17064     1 MKVIVKSLGGKGSLLRVDASETLESLKGKASKKLDDKPSEKVkLFYSGKELEDGKSLAEQNVPPNSLVHL 70

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 51.13 E-value: 2.17e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 560 TGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHK 614
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPK 61

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 51.02 E-value: 2.32e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPNlQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQ-VRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340505 [Multi-domain] Cd Length: 72 Bit Score: 50.82 E-value: 2.90e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 469 MQIFVKTFsfsgetpTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd01807     1 MLITVKIL-------QGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIH 68

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

Pssm-ID: 340642 Cd Length: 74 Bit Score: 50.64 E-value: 3.70e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  79 MQIFVQTLTGK-TITLEVKSSDT-IDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd17122     1 MWIQVRTMDGKeTHRIDSLSKLTkVEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLLVR 74

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340495 Cd Length: 74 Bit Score: 50.44 E-value: 3.92e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  79 MQIFVQTLTG-KTITLEVKSSDT-IDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd01797     1 MWIQVRTMDGkKEARVDGLSKLTkIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVGLNDIIQLMVR 74

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

Pssm-ID: 340508 [Multi-domain] Cd Length: 74 Bit Score: 50.53 E-value: 3.92e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqpNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHD--DQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNL 71

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 50.42 E-value: 4.27e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 489 TLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQkGSTIH 543
Cdd:cd01809    14 TFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVD-GKVIH 67

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

Pssm-ID: 340490 Cd Length: 75 Bit Score: 50.23 E-value: 5.28e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFR--GGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd01792     1 WDLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQQRLAVQpsGVELQDGVRLASQGLGPSSTVLL 71

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 49.98 E-value: 5.47e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493   2 TIQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVL 73
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340495 Cd Length: 74 Bit Score: 49.67 E-value: 7.05e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 393 MQIFVKLFGGKI-ITLEVLSSDT-IKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIR 454
Cdd:cd01797     1 MWIQVRTMDGKKeARVDGLSKLTkIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVG 64

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 49.63 E-value: 7.28e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 395 IFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHF 67

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 54.90 E-value: 7.75e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILP---RQQRLIFAGKQLEDGRTLADYNI 139
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAypvAQQKLIYSGKILSDDKTVKEYKI 64

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 49.59 E-value: 8.92e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 238 MYIFVKnlpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFRC 317
Cdd:cd01793     1 MQLFVR-------AQSLHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVRLLG 73


                  .
gi 1063710493 318 G 318
Cdd:cd01793    74 G 74

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 49.48 E-value: 9.96e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQ-RLIFAGKQLEDGLTLADYNIQKESTLHLVL 73
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 49.48 E-value: 1.05e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  79 MQIFVQTL-TGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQL-EDGRTLADYNIQ 140
Cdd:cd01796     1 MKLTVTTEdDDRLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLtDDKKTLEALGLK 64

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 49.09 E-value: 1.08e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 155 MQIFVSTFSGKNFTsdtltLKVESSDTIENVKAKIQDREGLRP-DHQRLIFHGEELftEDNRTLADYGI 222
Cdd:cd01805     1 MKITFKTLQQQTFE-----IEVEPSDTVLELKEKIEQEQGDFPaSGQKLIYSGKVL--KDDKTLSEYNI 62

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 49.21 E-value: 1.18e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 484 TCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTI 542
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPKGFVV 65

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 54.13 E-value: 1.31e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKP---DQQMLIFFGQQLEDGVTLGDYDIHKK 615
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAypvAQQKLIYSGKILSDDKTVKEYKIKEK 67

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 49.22 E-value: 1.36e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 321 IFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqpNLQRLIFLGKELKDGCTLADYSIQKESTLHLVLGMQI 395
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPP--DQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQGPKR 73

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 1 (UBTD1); UBTD1 is the mammalian homolog of the mitochondrial Dc-UbP/UBTD2 protein, both of which contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes. As a tumor suppressor, UBTD1 plays a pivotal role in in regulating cellular senescence that mediates p53 function. It is also involved in MDM2 ubiquitination and degradation.

Pssm-ID: 340640 Cd Length: 69 Bit Score: 48.78 E-value: 1.42e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493  83 VQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVL 149
Cdd:cd17120     3 VRLSTGKDVRLSASMSDTIGQLKKQLHAQEGIEPSWQRWFFSGKLLTDKTRLQETKIQKDFVIQVIV 69

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

Pssm-ID: 340584 [Multi-domain] Cd Length: 72 Bit Score: 48.98 E-value: 1.43e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFF-GQQLEDGVTLGDYDIHKKSTLYLV 621
Cdd:cd17064     1 MKVIVKSLGGKGSLLRVDASETLESLKGKASKKLDDKPSEKVKLFYsGKELEDGKSLAEQNVPPNSLVHLV 71

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 48.47 E-value: 1.79e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 481 ETPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd00196     4 ETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELH 66

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 48.81 E-value: 1.87e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493  83 VQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRL 151
Cdd:cd17052     4 VQSEEWDLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLKV 72

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 48.09 E-value: 2.31e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 168 TSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTL 228
Cdd:cd00196     7 SLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVL--DDLMTAKQVGLEPGEEL 65

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

Pssm-ID: 340503 [Multi-domain] Cd Length: 72 Bit Score: 47.94 E-value: 3.53e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 238 MYIFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKE-RIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTL 309
Cdd:cd01805     1 MKITFKTL-----QQQTFEIEVEPSDTVLELKEKIEQEQgDFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 47.56 E-value: 3.85e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQI-LLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQVrLIFDGERLDPNSTVEDLDIEDGDTIDV 70

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 47.95 E-value: 4.22e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  14 TITLDVETSDSIHNVKAKIQNKEGIPLDQQRL-IFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd01800    23 VLELTLPLTDTISVLKEKIHEELGMPANKQKLqVEGGGFLKDSNSLAFYNLGSGTVLTLSLK 84

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

Pssm-ID: 340490 Cd Length: 75 Bit Score: 47.53 E-value: 4.51e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493   4 QIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIF--AGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd01792     2 DLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQQRLAVqpSGVELQDGVRLASQGLGPSSTVLLVVK 74

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 47.62 E-value: 4.53e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493   2 TIQIYAKTLTEKTiTLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd01808     2 IIKVTVKTPKEKE-DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2, also termed Np95/ICBP90-like RING finger protein (NIRF), or Np95-likeRING finger protein, or nuclear protein 97, or nuclear zinc finger protein Np97, or RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131(ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340643 Cd Length: 74 Bit Score: 47.56 E-value: 5.05e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493   1 MTIQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd17123     1 MWIQVRTIDGTETQTIDDLSRLTKIESLREKIQELFNVRPERQRLFYRGKQLEDGHTLFDYNVGLNDIVQLLIR 74

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 48.05 E-value: 5.15e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 174 LKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELfTEDNRTLADYGIRNRSTLCL 230
Cdd:cd01795    10 LTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGREL-TDDSATLADLGILPGDVLYL 65

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 47.28 E-value: 5.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 319 MQIFVKTLTRKriNLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGCTLADYSIQKESTLHLvlgmqiFVK 398
Cdd:cd01793     1 MQLFVRAQSLH--TLEVSGNETVADIKAHIAALEGIAVED--QVLLYAGAPLEDDVVLGQCGIPDLATLEV------AVR 70


                  ....
gi 1063710493 399 LFGG 402
Cdd:cd01793    71 LLGG 74

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340495 Cd Length: 74 Bit Score: 47.36 E-value: 5.56e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTG-KTIILEVESSDT-IANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd01797     1 MWIQVRTMDGkKEARVDGLSKLTkIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVGLNDIIQLMVR 74

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 2 (UBTD2); UBTD2, also termed dendritic cell-derived ubiquitin-like protein (DC-UbP), or ubiquitin-like protein SB72, is a potential ubiquitin shuttle protein firstly identified in dendritic cells and implicated in apoptosis. It binds proteins involved in the ubiquitination pathway and may play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells. UBTD2 is expressed in tumor cells but not in normal human adult tissue suggesting a role in tumorogenesis. It can potentially regulate the stability of proteins involved in various physiological processes relevant to many disease phenotypes, such as ageing and cancer. UBTD2 reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes.

Pssm-ID: 340641 Cd Length: 75 Bit Score: 47.28 E-value: 5.92e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493  80 QIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVL 149
Cdd:cd17121     3 QLRLRLSTGKDLKLAVRSTDTVYHMKRRLHTAEGVEPGSQRWFFSGRPLTDKMKLEELKIPKDYVVQVIV 72

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

Pssm-ID: 340524 Cd Length: 70 Bit Score: 47.11 E-value: 6.21e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 240 IFVKNLpynsfTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLV 312
Cdd:cd16107     2 IFVRTY-----CGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

Pssm-ID: 340491 Cd Length: 74 Bit Score: 47.28 E-value: 6.45e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 469 MQIFVKTFSfsgetptckTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTI 542
Cdd:cd01793     1 MQLFVRAQS---------LHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATL 65

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 46.95 E-value: 7.30e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIrNESTLHL 461
Cdd:cd01809     1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDV-DGKVIHL 68

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 46.78 E-value: 7.33e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVSTFSGKNFtsdtLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELfTEDNRTLADYGIRN 224
Cdd:cd01796     1 MKLTVTTEDDDRL----FSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPL-TDDKKTLEALGLKD 65

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2, also termed Np95/ICBP90-like RING finger protein (NIRF), or Np95-likeRING finger protein, or nuclear protein 97, or nuclear zinc finger protein Np97, or RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131(ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340643 Cd Length: 74 Bit Score: 46.79 E-value: 8.25e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTGKTI--ILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd17123     1 MWIQVRTIDGTETqtIDDLSRLTKIESLREKIQELFNVRPERQRLFYRGKQLEDGHTLFDYNVGLNDIVQLLIR 74

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 46.55 E-value: 8.35e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 554 IFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLV 621
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

Pssm-ID: 340490 Cd Length: 75 Bit Score: 46.76 E-value: 9.03e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQ--QLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd01792     1 WDLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQQRLAVQPSgvELQDGVRLASQGLGPSSTVLLVVK 74

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 45.75 E-value: 1.68e-06

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 154 GMQIFVSTFSGKNFTsdtltLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLAL 232
Cdd:cd16103     1 EIQIFVKFPDGTSKP-----YAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQEL--RDKKSLKYYGIKDGDTLQLSL 72

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 46.51 E-value: 1.77e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 487 TITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVG-SRTLLDYNIQKGSTIH 543
Cdd:cd01795     7 RKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELTDdSATLADLGILPGDVLY 64

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 45.37 E-value: 2.47e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 395 IFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLH 460
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVH 66

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340495 Cd Length: 74 Bit Score: 45.05 E-value: 3.06e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  13 KTITLDVETSDS-IHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd01797    12 KEARVDGLSKLTkIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVGLNDIIQLMVR 74

ubiquitin-like (Ubl) domain 1 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which is required for its antiviral activity. This family corresponds to the first Ubl domain.

Pssm-ID: 340509 Cd Length: 75 Bit Score: 45.39 E-value: 3.09e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIF---AGKQ--LEDGRTLADYNIQKESTLHLV 148
Cdd:cd01811     1 IQVTVKQLGGKSLTLWVNPYDPIWQLKEEIEKEWCIPIYQQRLSFqepGGERqvLRNDKTLADYGIFYDTTILLL 75

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 44.62 E-value: 3.82e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 321 IFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQpnLQRLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPD--VIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 44.86 E-value: 3.95e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  12 EKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQL-EDGLTLADYNIQ 64
Cdd:cd01796    11 DRLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLtDDKKTLEALGLK 64

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 44.95 E-value: 4.56e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 486 KTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd17052    10 DLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIH 67

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 44.87 E-value: 4.87e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 166 NFTSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLiFHGEELFTEDNRTLADYGIRNRSTLCLALR 233
Cdd:cd01800    18 KLNGQVLELTLPLTDTISVLKEKIHEELGMPANKQKL-QVEGGGFLKDSNSLAFYNLGSGTVLTLSLK 84

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 44.59 E-value: 5.30e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 471 IFVKTFSfsgetptCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd01798     1 VFVRFNS-------SHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVH 66

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog A (HR23A); HR23A, also termed RAD23A, is a DNA repair protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation, which is required for efficient nucleotide excision repair (NER), a primary mechanism for removing UV-induced DNA lesions. HR23A also plays a critical role in the interaction of HIV-1 viral protein R (Vpr) with the proteasome, especially facilitating Vpr to promote protein poly-ubiquitination. HR23A contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340646 Cd Length: 76 Bit Score: 44.66 E-value: 5.30e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQ---NKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKES 67
Cdd:cd17126     1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEaekGRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKN 68

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340543 Cd Length: 78 Bit Score: 44.72 E-value: 5.92e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493   3 IQIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEG---IPLDQQRLIFAGKQLEDGLTLADYNIQKES 67
Cdd:cd16126     1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEKN 68

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 44.09 E-value: 8.33e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 238 MYIFVKNLPYNSFtgenFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEG-GRTLAHYNIQKGSTLYLV 312
Cdd:cd01796     1 MKLTVTTEDDDRL----FSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDdKKTLEALGLKDGDLLLLR 72

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 47.97 E-value: 1.24e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 393 MQIFVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGS---PPDQQILLFRGGQLQDGRTLGDYNI 453
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKdayPVAQQKLIYSGKILSDDKTVKEYKI 64

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 44.20 E-value: 1.25e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  87 TGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGR-TLADYNIQKESTLHLV 148
Cdd:cd01795     4 RGERKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELTDDSaTLADLGILPGDVLYLK 66

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 43.39 E-value: 1.27e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493  81 IFVQTLTGKTiTLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd01808     5 VTVKTPKEKE-DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

Pssm-ID: 340642 Cd Length: 74 Bit Score: 43.32 E-value: 1.28e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063710493  25 IHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd17122    25 VEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLLVR 74

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 43.72 E-value: 1.32e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 487 TITLEVESSDTIDNVKVKIQHKVGIPLDRQRL-IFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd01800    23 VLELTLPLTDTISVLKEKIHEELGMPANKQKLqVEGGGFLKDSNSLAFYNLGSGTVLT 80

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 44.20 E-value: 1.32e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 402 GKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQL-QDGRTLGDYNIRNESTLHL 461
Cdd:cd01795     5 GERKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELtDDSATLADLGILPGDVLYL 65

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 43.44 E-value: 1.38e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 240 IFVKNLPynsftGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYL 311
Cdd:cd16103     4 IFVKFPD-----GTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQL 70

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 43.41 E-value: 1.46e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 402 GKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd17052     9 WDLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHL 68

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 43.32 E-value: 1.50e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 469 MQIFVKTfsfsgetPTCKTITLEVESSDTIDNVKVKIQHKVGIP-LDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:pfam11976   1 IKIILKG-------KDGKEVFIKVKPTTTVSKLINAYRKKRGIPpSQQVRLIFDGERLDPNSTVEDLDIEDGDTID 69

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 43.39 E-value: 1.51e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 406 TLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHL 461
Cdd:cd01808    15 DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHL 70

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340497 Cd Length: 81 Bit Score: 43.36 E-value: 1.52e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  90 TITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFaGKQL-EDGRTLADYNIQKEST---LHLV 148
Cdd:cd01799    18 PITLKVRPHTTIASLKRQIFLEYGFPPSVQRWII-GKRLaTDDETLLSYGIKDSGDpafLYLV 79

ubiquitin-like (Ubl) domain 1 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which is required for its antiviral activity. This family corresponds to the first Ubl domain.

Pssm-ID: 340509 Cd Length: 75 Bit Score: 43.08 E-value: 1.80e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 171 TLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFH---GEELFTEDNRTLADYGIRNRSTLCL 230
Cdd:cd01811    12 SLTLWVNPYDPIWQLKEEIEKEWCIPIYQQRLSFQepgGERQVLRNDKTLADYGIFYDTTILL 74

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340497 Cd Length: 81 Bit Score: 42.97 E-value: 2.21e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 487 TITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQK-GSTIhQLFL 547
Cdd:cd01799    18 PITLKVRPHTTIASLKRQIFLEYGFPPSVQRWIIGKRLATDDETLLSYGIKDsGDPA-FLYL 78

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 42.62 E-value: 2.52e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 554 IFIKTLTGKTIIlEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd01808     5 VTVKTPKEKEDF-EVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 42.54 E-value: 2.84e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 469 MQIFVkTFSFSGetptcKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVG-SRTLLDYNIQKGSTI 542
Cdd:cd01796     1 MKLTV-TTEDDD-----RLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDdKKTLEALGLKDGDLL 69

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 1 (UBTD1); UBTD1 is the mammalian homolog of the mitochondrial Dc-UbP/UBTD2 protein, both of which contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes. As a tumor suppressor, UBTD1 plays a pivotal role in in regulating cellular senescence that mediates p53 function. It is also involved in MDM2 ubiquitination and degradation.

Pssm-ID: 340640 Cd Length: 69 Bit Score: 42.23 E-value: 2.97e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  11 TEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVL 73
Cdd:cd17120     7 TGKDVRLSASMSDTIGQLKKQLHAQEGIEPSWQRWFFSGKLLTDKTRLQETKIQKDFVIQVIV 69

ubiquitin-like (Ubl) domain found in tubulin-folding cofactor B (TBCB) and similar proteins; TBCB, also termed cytoskeleton-associated protein 1, or cytoskeleton-associated protein CKAPI, or tubulin-specific chaperone B, is one of protein cofactors A through E that is required for the folding of tubulins prior to their incorporation into microtubules and heterodimer assembly. TBCB comprises an N-terminal ubiquitin-like (Ubl) domain and a C-terminal cytoskeleton-associated protein with glycine-rich segment (CAP-Gly) domain. The Ubl domain of TBCB is essential for proper folding and assembly of tubulin alpha. It has a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. TBC-A through E are necessary for the biogenesis of microtubules and for cell viability.

Pssm-ID: 340487 Cd Length: 80 Bit Score: 42.56 E-value: 3.07e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 412 SDTIKSVKAKIQDKVGSPPD-QQILLF--RGGQL----QDGRTLGDYNIRNESTLH 460
Cdd:cd01789    22 SLTIGELKEKLELITGTPPSsMKLQLYdeDGKLIgtldDDDALLGSYPVRDGMRIH 77

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 2 (UBTD2); UBTD2, also termed dendritic cell-derived ubiquitin-like protein (DC-UbP), or ubiquitin-like protein SB72, is a potential ubiquitin shuttle protein firstly identified in dendritic cells and implicated in apoptosis. It binds proteins involved in the ubiquitination pathway and may play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells. UBTD2 is expressed in tumor cells but not in normal human adult tissue suggesting a role in tumorogenesis. It can potentially regulate the stability of proteins involved in various physiological processes relevant to many disease phenotypes, such as ageing and cancer. UBTD2 reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes.

Pssm-ID: 340641 Cd Length: 75 Bit Score: 42.27 E-value: 3.10e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 553 QIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHK 614
Cdd:cd17121     3 QLRLRLSTGKDLKLAVRSTDTVYHMKRRLHTAEGVEPGSQRWFFSGRPLTDKMKLEELKIPK 64

ubiquitin-like (Ubl) domain 1 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which is required for its antiviral activity. This family corresponds to the first Ubl domain.

Pssm-ID: 340509 Cd Length: 75 Bit Score: 42.30 E-value: 3.12e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIF-----FGQQLEDGVTLGDYDIHKKSTLYLV 621
Cdd:cd01811     1 IQVTVKQLGGKSLTLWVNPYDPIWQLKEEIEKEWCIPIYQQRLSFqepggERQVLRNDKTLADYGIFYDTTILLL 75

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 42.16 E-value: 3.38e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 393 MQIFVK-LFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQ-DGRTLGDYNIRNESTL 459
Cdd:cd01796     1 MKLTVTtEDDDRLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTdDKKTLEALGLKDGDLL 69

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 46.43 E-value: 3.81e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 469 MQIFVKTFSFSgetptckTITLEVESSDTIDNVKVKIQHKVG---IPLDRQRLIFGGRVLVGSRTLLDYNIQKG 539
Cdd:TIGR00601   1 MTLTFKTLQQQ-------KFKIDMEPDETVKELKEKIEAEQGkdaYPVAQQKLIYSGKILSDDKTVKEYKIKEK 67

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 42.16 E-value: 3.96e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 552 MQIFIKTL-TGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGV-TLGDYDIHKKSTLYLV 621
Cdd:cd01796     1 MKLTVTTEdDDRLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDDKkTLEALGLKDGDLLLLR 72

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

Pssm-ID: 340450 Cd Length: 68 Bit Score: 41.54 E-value: 4.94e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 251 TGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLV 312
Cdd:cd00196     7 SLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 46.04 E-value: 5.08e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 244 NLPYNSFTGENFILEVESSDTIDNVKAKLQD---KERIPMDLHRLIFAGKPLEGGRTLAHYNI-QKGSTLYLVTR 314
Cdd:TIGR00601   2 TLTFKTLQQQKFKIDMEPDETVKELKEKIEAeqgKDAYPVAQQKLIYSGKILSDDKTVKEYKIkEKDFVVVMVSK 76

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 41.51 E-value: 5.80e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 318 GMQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGiqPQPNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGG--PPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 1 (UBTD1); UBTD1 is the mammalian homolog of the mitochondrial Dc-UbP/UBTD2 protein, both of which contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes. As a tumor suppressor, UBTD1 plays a pivotal role in in regulating cellular senescence that mediates p53 function. It is also involved in MDM2 ubiquitination and degradation.

Pssm-ID: 340640 Cd Length: 69 Bit Score: 41.46 E-value: 5.91e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 560 TGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHK 614
Cdd:cd17120     7 TGKDVRLSASMSDTIGQLKKQLHAQEGIEPSWQRWFFSGKLLTDKTRLQETKIQK 61

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 42.27 E-value: 6.22e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493  14 TITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGL-TLADYNIQKESTLHLV 72
Cdd:cd01795     7 RKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELTDDSaTLADLGILPGDVLYLK 66

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 41.50 E-value: 6.25e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 168 TSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLAD 219
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLL--TDKTRIED 56

ubiquitin-like (Ubl) domain 1 found in Ankyrin repeat and ubiquitin domain-containing 1 (ANKUB1) and similar proteins; ANKUB1 is an uncharacterized protein with two tandem ubiquitin-like (Ubl) domains located at the N-terminal of Ankyrin repeats (ANK). The Ubl domain may have an adaptor role in ubiquitin (Ub)-signaling by mediating protein-protein interaction. Ubl proteins have a beta-grasp Ubl fold and attach to other proteins in a Ubl manner with biochemically distinct roles. The ankyrin repeats have been identified in numerous proteins with diverse functions. The family corresponds to the first Ubl domain.

Pssm-ID: 340570 Cd Length: 79 Bit Score: 41.52 E-value: 6.48e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493  79 MQIFVqTLTGKTITLEVKSSDTIDNVKAKIQDKEGILPRQQR-------LIFAGKQLEDGRTLADYNIQKESTLHLVLR 150
Cdd:cd17050     1 MRIFV-AFEGEREPLDVSPGQTVGDVKEMIRDKFHIDLSDGKqgrkflvLTYAGADLQDSWVLSDIGIPPGSTIRCLLR 78

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

Pssm-ID: 340523 [Multi-domain] Cd Length: 73 Bit Score: 41.09 E-value: 7.51e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 168 TSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRN 224
Cdd:cd16106     9 NGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKIL--KDEETLSSYKIQD 63

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog A (HR23A); HR23A, also termed RAD23A, is a DNA repair protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation, which is required for efficient nucleotide excision repair (NER), a primary mechanism for removing UV-induced DNA lesions. HR23A also plays a critical role in the interaction of HIV-1 viral protein R (Vpr) with the proteasome, especially facilitating Vpr to promote protein poly-ubiquitination. HR23A contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340646 Cd Length: 76 Bit Score: 41.20 E-value: 7.77e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQV---KEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKS 616
Cdd:cd17126     1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAekgRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKN 68

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

Pssm-ID: 340490 Cd Length: 75 Bit Score: 41.37 E-value: 8.61e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 155 MQIFVSTFSGKNFTsdtltLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELFTEDNRTLADYGIRNRSTLCL 230
Cdd:cd01792     1 WDLTVKMLTGNEFQ-----VSVSPSMTVSELKAQITQKIGVPAFQQRLAVQPSGVELQDGVRLASQGLGPSSTVLL 71

ubiquitin-like (Ubl) domain found in plant membrane-anchored ubiquitin-fold proteins (MUBs); The plant MUBs belong to a family of ubiquitin-fold proteins that are plasma membrane-anchored by prenylation. They may serve as docking site to facilitate the association of specific E2s to the plasma membrane. MUBs contain a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold.

Pssm-ID: 340512 Cd Length: 89 Bit Score: 41.60 E-value: 9.14e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493  97 SSDTIDNVKAKI-----QDKEGIL--PRQQRLIFAGKQLEDGRTLADYN-IQKES-----TLHLVLR 150
Cdd:cd01814    21 SATTVATLKEKViaewpKDKENGPksINDVKLIYAGKVLENGKTLADSRtPGKVPpggviTMHVVVR 87

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 2 (UBTD2); UBTD2, also termed dendritic cell-derived ubiquitin-like protein (DC-UbP), or ubiquitin-like protein SB72, is a potential ubiquitin shuttle protein firstly identified in dendritic cells and implicated in apoptosis. It binds proteins involved in the ubiquitination pathway and may play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells. UBTD2 is expressed in tumor cells but not in normal human adult tissue suggesting a role in tumorogenesis. It can potentially regulate the stability of proteins involved in various physiological processes relevant to many disease phenotypes, such as ageing and cancer. UBTD2 reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes.

Pssm-ID: 340641 Cd Length: 75 Bit Score: 41.11 E-value: 9.68e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493   4 QIYAKTLTEKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLHLVL 73
Cdd:cd17121     3 QLRLRLSTGKDLKLAVRSTDTVYHMKRRLHTAEGVEPGSQRWFFSGRPLTDKMKLEELKIPKDYVVQVIV 72

ubiquitin-like (Ubl) domain 1 found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin (Ub) regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) fold, but without the C-terminal double glycine motif. The UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, FAF1 contains two tandem Ubl domains, which show high structural similarity with the UBX domain. FAF1 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. The family corresponds to the first Ubl domain.

Pssm-ID: 340649 Cd Length: 73 Bit Score: 41.09 E-value: 9.74e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493  12 EKTITLDVETSDSIHNVKAKIQNKEGIPLDQQRLI-FAGKQLEDGLTLADYNIQKESTLHLV 72
Cdd:cd17129    10 DRTIDVVLPDTETVGDIKQILENELGIPPCKQILKgWKARTVSDSTVLRSLHLPKENSLYLL 71

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

Pssm-ID: 340520 [Multi-domain] Cd Length: 72 Bit Score: 40.74 E-value: 1.00e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 468 GMQIFVKTfsfsgetPTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIhQLFL 547
Cdd:cd16103     1 EIQIFVKF-------PDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTL-QLSL 72

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 273167 [Multi-domain] Cd Length: 378 Bit Score: 44.50 E-value: 1.31e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQP-NLQRLIFLGKELKDGCTLADYSI 381
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPvAQQKLIYSGKILSDDKTVKEYKI 64

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

Pssm-ID: 340642 Cd Length: 74 Bit Score: 40.63 E-value: 1.39e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 393 MQIFVKLFGGKII-TLEVLSSDT-IKSVKAKIQDKVGSPPDQQILLFRGGQLQDGRTLGDYNIRNESTLHLF 462
Cdd:cd17122     1 MWIQVRTMDGKEThRIDSLSKLTkVEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLL 72

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), which may function in the regulation of cell cycle progression. NUB1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

Pssm-ID: 340582 Cd Length: 78 Bit Score: 40.58 E-value: 1.49e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493  91 ITLEVKSSDTIDNVKAKIQDKEGILPRQQRLIFAGKQLEDGRTLADYNIQKESTLhLVLRL 151
Cdd:cd17062    19 ITLETSLDITGSELREKIAEELGVPEDRIKLISNGKVLKDEKTLAEQGVKNNSQV-MVLVL 78

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 39.96 E-value: 1.69e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 327 TRKRINLEVESWDTIENVKAMVQDKEGIqpQPNLQRLIFLGKELKDGCTLADYSIQK 383
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGI--EPSRQRWFFSGKLLTDKTRIEDAKIPK 61

ubiquitin-like (Ubl) domain found in midnolin and similar proteins; Midnolin, also termed midbrain nucleolar protein, is a nucleolar protein that may be involved in regulation of genes related to neurogenesis in the nucleolus. It is strongly expressed at the mesencephalon (midbrain) of the embryo in day 12.5 (E12.5) mice and its expression is developmentally regulated. Midnolin plays a role in cellular signaling of adult tissues and regulates glucokinase enzyme activity in pancreatic beta cells. It can also control development via regulation of mRNA transport in cells. Midnolin contains an N-terminal conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340502 Cd Length: 70 Bit Score: 39.94 E-value: 1.76e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 244 NLPYNSFTGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGrTLAHYNIQKGSTLYLV 312
Cdd:cd01804     2 NLYIHPTTGGRFELSVPPNETVEGLKRRISKKLKVPKERITLLHKEKQLKDG-TLRENGIGDGSKLTLL 69

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340497 Cd Length: 81 Bit Score: 40.27 E-value: 1.85e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 169 SDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFhGEELFTeDNRTLADYGIRN 224
Cdd:cd01799    16 SGPITLKVRPHTTIASLKRQIFLEYGFPPSVQRWII-GKRLAT-DDETLLSYGIKD 69

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 40.73 E-value: 1.93e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 560 TGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGV-TLGDYDIHKKSTLYLV 621
Cdd:cd01795     4 RGERKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELTDDSaTLADLGILPGDVLYLK 66

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 39.92 E-value: 2.45e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 258 EVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTR 314
Cdd:cd01808    17 EVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340492 Cd Length: 69 Bit Score: 39.58 E-value: 2.50e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 251 TGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKG 306
Cdd:cd01794     7 TGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPKG 62

ubiquitin-like (Ubl) domain found in ubiquitin-like domain-containing CTD phosphatase 1 (UBLCP1) and similar proteins; UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity. It is localized in the nucleus and it contains conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which directly interacts with the proteasome. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. UBLCP1 may also play a role in the regulation of phosphorylation state of RNA polymerase II C-terminal domain, a key event during mRNA metabolism.

Pssm-ID: 340511 Cd Length: 74 Bit Score: 39.86 E-value: 2.52e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  88 GKTITLEVKSSDTIDNVKAKIQDKEGILPRQQRLI---FAGKQLEDGRTLADYNIQ 140
Cdd:cd01813     9 GKEYPVTVLSSDTVLDLKQRIFELTGVLPKRQKLLglkVKGKPADDDVKLSSLKLK 64

ubiquitin-like (Ubl) domain found in homocysteine-inducible endoplasmic reticulum stress protein HERP; HERP is an endoplasmic reticulum (ER) integral membrane protein containing an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. The Ubl domain is required for the degradation of HERP itself as well as for HERP-mediated anti-apoptotic effects. HERP is induced by the ER stress response pathway and is involved in improving the balance of folding capacity and protein loads in the ER. There are two types of HERP, HERP1 and HERP2, which are encoded by the HERPUD1 and HERPUD2 genes, respectively.

Pssm-ID: 340488 Cd Length: 78 Bit Score: 39.93 E-value: 2.74e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  16 TLDVETSDSIHNVKAKIQNK-EGIPL-DQQRLIFAGKQLEDGLTLADYNIQKES----TLHLV 72
Cdd:cd01790    16 TVNCTLGWTVLKLKEHLSEVyPSKPLpEDQKLIYSGKLLEDHQTLKDVLREDDPeqvhTVHLV 78

Ubiquitin-like domain; This entry contains ubiquitin-like domains.

Pssm-ID: 405277 Cd Length: 83 Bit Score: 39.82 E-value: 2.80e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 411 SSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQ-------DGRTLGDYNIRNESTLH 460
Cdd:pfam14560  21 KSLTIEELKEKLELITGTPPSSMRLQLYDDDDNlvaklddDDALLGSYGVRDGMRIH 77

ubiquitin-like (Ubl) domain 1 found in Ankyrin repeat and ubiquitin domain-containing 1 (ANKUB1) and similar proteins; ANKUB1 is an uncharacterized protein with two tandem ubiquitin-like (Ubl) domains located at the N-terminal of Ankyrin repeats (ANK). The Ubl domain may have an adaptor role in ubiquitin (Ub)-signaling by mediating protein-protein interaction. Ubl proteins have a beta-grasp Ubl fold and attach to other proteins in a Ubl manner with biochemically distinct roles. The ankyrin repeats have been identified in numerous proteins with diverse functions. The family corresponds to the first Ubl domain.

Pssm-ID: 340570 Cd Length: 79 Bit Score: 39.98 E-value: 2.82e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  16 TLDVETSDSIHNVKAKIQNKEGIPLDQQR-------LIFAGKQLEDGLTLADYNIQKESTLHLVLR 74
Cdd:cd17050    13 PLDVSPGQTVGDVKEMIRDKFHIDLSDGKqgrkflvLTYAGADLQDSWVLSDIGIPPGSTIRCLLR 78

ubiquitin-like (Ubl) domain found in ubiquitin-like domain-containing CTD phosphatase 1 (UBLCP1) and similar proteins; UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity. It is localized in the nucleus and it contains conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which directly interacts with the proteasome. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. UBLCP1 may also play a role in the regulation of phosphorylation state of RNA polymerase II C-terminal domain, a key event during mRNA metabolism.

Pssm-ID: 340511 Cd Length: 74 Bit Score: 39.09 E-value: 4.19e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 561 GKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLI---FFGQQLEDGVTLGD 609
Cdd:cd01813     9 GKEYPVTVLSSDTVLDLKQRIFELTGVLPKRQKLLglkVKGKPADDDVKLSS 60

ubiquitin-like (Ubl) domain 1 found in Ankyrin repeat and ubiquitin domain-containing 1 (ANKUB1) and similar proteins; ANKUB1 is an uncharacterized protein with two tandem ubiquitin-like (Ubl) domains located at the N-terminal of Ankyrin repeats (ANK). The Ubl domain may have an adaptor role in ubiquitin (Ub)-signaling by mediating protein-protein interaction. Ubl proteins have a beta-grasp Ubl fold and attach to other proteins in a Ubl manner with biochemically distinct roles. The ankyrin repeats have been identified in numerous proteins with diverse functions. The family corresponds to the first Ubl domain.

Pssm-ID: 340570 Cd Length: 79 Bit Score: 39.20 E-value: 4.34e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 393 MQIFVkLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQ-------ILLFRGGQLQDGRTLGDYNIRNESTL 459
Cdd:cd17050     1 MRIFV-AFEGEREPLDVSPGQTVGDVKEMIRDKFHIDLSDGkqgrkflVLTYAGADLQDSWVLSDIGIPPGSTI 73

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

Pssm-ID: 403255 [Multi-domain] Cd Length: 72 Bit Score: 39.08 E-value: 4.35e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 155 MQIFVSTFSGKnftsdTLTLKVESSDTIENVKAKIQDREGLRPDHQ-RLIFHGEELftEDNRTLADYGIRNRSTL 228
Cdd:pfam11976   1 IKIILKGKDGK-----EVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERL--DPNSTVEDLDIEDGDTI 68

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 38.86 E-value: 4.60e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPqpNLQRLIFLGKELKDGCTLADYSIQkESTLHLV 390
Cdd:cd01809     1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPA--EKQRLIFQGRVLQDDKKLKEYDVD-GKVIHLV 69

ubiquitin-like (Ubl) domain found in non-canonical Inhibitor of kappa B kinases IKKepsilon and TBK1, and similar proteins; IKKepsilon and TBK1 (TRAF family member-associated NF-kappaB activator-binding kinase 1) are non-canonical members of IKK family. They have been characterized as activators of nuclear factor-kappaB (NF-kappaB), but they are not essential for NF-kappaB activation. They play critical roles in antiviral response via phosphorylation and activation of transcription factors IRF3, IRF7, STAT1 and STAT3. They are also involved in the survival, tumorigenesis and development of various cancers. Both IKKepsilon and TBK1 contain an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

Pssm-ID: 340518 Cd Length: 77 Bit Score: 39.14 E-value: 4.68e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063710493 558 TLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTL 607
Cdd:cd12219     9 VSTCELLKIYLDPTETLAEFQELIAEQTEIPAKNQLLLFEGQLLEEEVTL 58

ubiquitin-like (Ubl) domain found in plant membrane-anchored ubiquitin-fold proteins (MUBs); The plant MUBs belong to a family of ubiquitin-fold proteins that are plasma membrane-anchored by prenylation. They may serve as docking site to facilitate the association of specific E2s to the plasma membrane. MUBs contain a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold.

Pssm-ID: 340512 Cd Length: 89 Bit Score: 39.28 E-value: 4.77e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493  24 SIHNVKAKI-----QNKEGIPLDQQ--RLIFAGKQLEDGLTLADYN-IQKES-----TLHLVLRLR 76
Cdd:cd01814    24 TVATLKEKViaewpKDKENGPKSINdvKLIYAGKVLENGKTLADSRtPGKVPpggviTMHVVVRPP 89

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340495 Cd Length: 74 Bit Score: 38.89 E-value: 5.06e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 319 MQIFVKTLT-RKRINLEVESWDT-IENVKAMVQDKEGIQPQpnLQRLIFLGKELKDGCTLADYSI 381
Cdd:cd01797     1 MWIQVRTMDgKKEARVDGLSKLTkIEDLRERIEEKFDVEPE--LQRLFYRGKQLEDGHTLFDYDV 63

ubiquitin-like (Ubl) domain found in homocysteine-inducible endoplasmic reticulum stress protein HERP; HERP is an endoplasmic reticulum (ER) integral membrane protein containing an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. The Ubl domain is required for the degradation of HERP itself as well as for HERP-mediated anti-apoptotic effects. HERP is induced by the ER stress response pathway and is involved in improving the balance of folding capacity and protein loads in the ER. There are two types of HERP, HERP1 and HERP2, which are encoded by the HERPUD1 and HERPUD2 genes, respectively.

Pssm-ID: 340488 Cd Length: 78 Bit Score: 38.77 E-value: 5.54e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  92 TLEVKSSDTIDNVKAKIQDK--EGILPRQQRLIFAGKQLEDGRTLADYNIQKES----TLHLV 148
Cdd:cd01790    16 TVNCTLGWTVLKLKEHLSEVypSKPLPEDQKLIYSGKLLEDHQTLKDVLREDDPeqvhTVHLV 78

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

Pssm-ID: 340642 Cd Length: 74 Bit Score: 38.70 E-value: 5.70e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 552 MQIFIKTLTGKTIiLEVESSDTIANVKE---KIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd17122     1 MWIQVRTMDGKET-HRIDSLSKLTKVEElrqKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLLVR 74

ubiquitin-like (Ubl) domain 1 found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin (Ub) regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) fold, but without the C-terminal double glycine motif. The UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, FAF1 contains two tandem Ubl domains, which show high structural similarity with the UBX domain. FAF1 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. The family corresponds to the first Ubl domain.

Pssm-ID: 340649 Cd Length: 73 Bit Score: 38.78 E-value: 5.76e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063710493 403 KIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILL-FRGGQLQDGRTLGDYNIRNESTLHLF 462
Cdd:cd17129    11 RTIDVVLPDTETVGDIKQILENELGIPPCKQILKgWKARTVSDSTVLRSLHLPKENSLYLL 71

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 38.79 E-value: 6.21e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493 561 GKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYLVLRL 624
Cdd:cd17052     9 WDLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLKV 72

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340496 Cd Length: 74 Bit Score: 38.43 E-value: 6.94e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 240 IFVKnlpYNSftGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTR 314
Cdd:cd01798     1 VFVR---FNS--SHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQG 70

ubiquitin-like (Ubl) domain found in ubiquitin-like protein 5 (UBL5) and similar proteins; UBL5, known as Hub1 in yeast, is an atypical ubiquitin-like (Ubl) post-translational modifier that contains a conserved Ubl domain with a beta-grasp Ubl fold. At the C-terminal end of its Ubl fold is a di-tyrosine motif followed by a single variable residue instead of the characteristic di-glycine found in all other Ubl modifiers, and thus UBL5 does not form covalent conjugates with cellular proteins. The yeast Hub1p binds non-covalently to the HIND element of spliceosomal protein Snu66p (Snu66p is termed SART1 in mammals) and modifies the spliceosome by this unconventional Ubl modifier. In higher eukaryotes, UBL5/Hub1 plays a role in modulating pre-mRNA splicing. It also is required for signaling in the mitochondrial unfolded protein response, through interaction with the transcription factor DVE-1 and upregulation of chaperone genes in response to mitochondrial stress. Moreover, UBL5 functions as a factor that directly binds to and stabilizes FANCI, and promotes the functionality of the Fanconi anemia (FA) DNA repair pathway.

Pssm-ID: 340489 Cd Length: 71 Bit Score: 38.45 E-value: 7.88e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 561 GKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIFFGQQLEDGVTLGDYDIHKKSTLYL 620
Cdd:cd01791    11 GKKVRVKCNPDDTIGDLKKLIAAQTGTRPEKIVLKKWYTIFKDHITLEDYEIHDGMNLEL 70

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 1 (UBTD1); UBTD1 is the mammalian homolog of the mitochondrial Dc-UbP/UBTD2 protein, both of which contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes. As a tumor suppressor, UBTD1 plays a pivotal role in in regulating cellular senescence that mediates p53 function. It is also involved in MDM2 ubiquitination and degradation.

Pssm-ID: 340640 Cd Length: 69 Bit Score: 38.38 E-value: 8.46e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 323 VKTLTRKRINLEVESWDTIENVKAMVQDKEGIqpQPNLQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd17120     3 VRLSTGKDVRLSASMSDTIGQLKKQLHAQEGI--EPSWQRWFFSGKLLTDKTRLQETKIQKDFVIQVIV 69

ubiquitin-like (Ubl) domain 1 found in Ankyrin repeat and ubiquitin domain-containing 1 (ANKUB1) and similar proteins; ANKUB1 is an uncharacterized protein with two tandem ubiquitin-like (Ubl) domains located at the N-terminal of Ankyrin repeats (ANK). The Ubl domain may have an adaptor role in ubiquitin (Ub)-signaling by mediating protein-protein interaction. Ubl proteins have a beta-grasp Ubl fold and attach to other proteins in a Ubl manner with biochemically distinct roles. The ankyrin repeats have been identified in numerous proteins with diverse functions. The family corresponds to the first Ubl domain.

Pssm-ID: 340570 Cd Length: 79 Bit Score: 38.43 E-value: 9.23e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 552 MQIFIkTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQM-------LIFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd17050     1 MRIFV-AFEGEREPLDVSPGQTVGDVKEMIRDKFHIDLSDGKqgrkflvLTYAGADLQDSWVLSDIGIPPGSTIRCLLR 78

ubiquitin-like (Ubl) domain found in ubiquitin-like protein 7 (UBL7) and similar proteins; UBL7, also termed bone marrow stromal cell ubiquitin-like (Ubl)protein (BMSC-UbP), or ubiquitin-like protein SB132, is a novel Ubl protein that may play roles in regulation of bone marrow stromal cell (BMSC) function or cell differentiation via an evocator-associated and cell-specific pattern. UBL7 contains an N-terminal Ubl domain with a beta-grasp Ubl fold, and a C-terminal ubiquitin-associated (UBA) domain. The Ubl domain interacts with 26S proteasome-dependent degradation, and the UBA domain links cellular processes and the ubiquitin system.

Pssm-ID: 340513 Cd Length: 92 Bit Score: 38.69 E-value: 9.45e-04

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1063710493 356 PQPNLQRLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd01815    50 PDPELIDLIYCGRKLKDDQTLDFYGIQSGSTIHVL 84

ubiquitin-like (Ubl) domain found in non-canonical Inhibitor of kappa B kinases IKKepsilon and TBK1, and similar proteins; IKKepsilon and TBK1 (TRAF family member-associated NF-kappaB activator-binding kinase 1) are non-canonical members of IKK family. They have been characterized as activators of nuclear factor-kappaB (NF-kappaB), but they are not essential for NF-kappaB activation. They play critical roles in antiviral response via phosphorylation and activation of transcription factors IRF3, IRF7, STAT1 and STAT3. They are also involved in the survival, tumorigenesis and development of various cancers. Both IKKepsilon and TBK1 contain an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

Pssm-ID: 340518 Cd Length: 77 Bit Score: 37.98 E-value: 1.09e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 473 VKTFSFSgetpTCKTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIHQLFL 547
Cdd:cd12219     4 IHVFSVS----TCELLKIYLDPTETLAEFQELIAEQTEIPAKNQLLLFEGQLLEEEVTLPVSDYPKTTEENPIIL 74

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340543 Cd Length: 78 Bit Score: 38.17 E-value: 1.11e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQDKEG--ILP-RQQRLIFAGKQLEDGRTLADYNIQKES 143
Cdd:cd16126     1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdAFPvAGQKLIYAGKILNDDTALKEYKIDEKN 68

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 37.94 E-value: 1.24e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 331 INLEVESWDTIENVKAMVQDKEGIqPqPNLQRL-IFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd01800    24 LELTLPLTDTISVLKEKIHEELGM-P-ANKQKLqVEGGGFLKDSNSLAFYNLGSGTVLTLSL 83

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340543 Cd Length: 78 Bit Score: 37.78 E-value: 1.42e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 552 MQIFIKTLTGKTIILEVESSDTIANVKEKIQVKEG---IKPDQQMLIFFGQQLEDGVTLGDYDIHKKS 616
Cdd:cd16126     1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEKN 68

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog A (HR23A); HR23A, also termed RAD23A, is a DNA repair protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation, which is required for efficient nucleotide excision repair (NER), a primary mechanism for removing UV-induced DNA lesions. HR23A also plays a critical role in the interaction of HIV-1 viral protein R (Vpr) with the proteasome, especially facilitating Vpr to promote protein poly-ubiquitination. HR23A contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340646 Cd Length: 76 Bit Score: 37.73 E-value: 1.46e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493  79 MQIFVQTLTGKTITLEVKSSDTIDNVKAKIQD---KEGILPRQQRLIFAGKQLEDGRTLADYNIQKES 143
Cdd:cd17126     1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAekgRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKN 68

ubiquitin-like (Ubl) domain 1 found in Ankyrin repeat and ubiquitin domain-containing 1 (ANKUB1) and similar proteins; ANKUB1 is an uncharacterized protein with two tandem ubiquitin-like (Ubl) domains located at the N-terminal of Ankyrin repeats (ANK). The Ubl domain may have an adaptor role in ubiquitin (Ub)-signaling by mediating protein-protein interaction. Ubl proteins have a beta-grasp Ubl fold and attach to other proteins in a Ubl manner with biochemically distinct roles. The ankyrin repeats have been identified in numerous proteins with diverse functions. The family corresponds to the first Ubl domain.

Pssm-ID: 340570 Cd Length: 79 Bit Score: 37.66 E-value: 1.65e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 319 MQIFVkTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPNLQRLIFL-----GKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd17050     1 MRIFV-AFEGEREPLDVSPGQTVGDVKEMIRDKFHIDLSDGKQGRKFLvltyaGADLQDSWVLSDIGIPPGSTIRCLL 77

ubiquitin-like (Ubl) domain 1 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which is required for its antiviral activity. This family corresponds to the first Ubl domain.

Pssm-ID: 340509 Cd Length: 75 Bit Score: 37.30 E-value: 1.87e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 486 KTITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIF---GG--RVLVGSRTLLDYNIQKGSTIHQL 545
Cdd:cd01811    11 KSLTLWVNPYDPIWQLKEEIEKEWCIPIYQQRLSFqepGGerQVLRNDKTLADYGIFYDTTILLL 75

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 37.25 E-value: 1.88e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 252 GENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQKGSTLYLVTRFRC 317
Cdd:cd17052     9 WDLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLKVVK 74

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 37.22 E-value: 1.93e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 482 TPTCKTiTLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTIH 543
Cdd:cd01808     9 TPKEKE-DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVH 69

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein UBFD1 and similar proteins; UBFD1, also termed ubiquitin-binding protein homolog (UBPH), is a polyubiquitin binding protein containing a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. It may play a role as nuclear factor-kappaB (NF-kappaB) regulator.

Pssm-ID: 340567 Cd Length: 70 Bit Score: 37.22 E-value: 1.94e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 396 FVKLFGGKIITLEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRgGQLQDGRTLGD 450
Cdd:cd17047     3 FKVIWNKEKYDVKFPLDSTIAELKEHIETLTGVPPAMQKLMYK-GLLKDDKTLRE 56

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340498 Cd Length: 84 Bit Score: 37.55 E-value: 2.04e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 559 LTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQML-IFFGQQLEDGVTLGDYDIHKKSTLYLVLR 623
Cdd:cd01800    19 LNGQVLELTLPLTDTISVLKEKIHEELGMPANKQKLqVEGGGFLKDSNSLAFYNLGSGTVLTLSLK 84

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

Pssm-ID: 340495 Cd Length: 74 Bit Score: 37.35 E-value: 2.08e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063710493 469 MQIFVKTFSFSgetptcKTITLEVESSDT-IDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNI 536
Cdd:cd01797     1 MWIQVRTMDGK------KEARVDGLSKLTkIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDV 63

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), which may function in the regulation of cell cycle progression. NUB1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

Pssm-ID: 340582 Cd Length: 78 Bit Score: 37.12 E-value: 2.12e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493   1 MTIQIYAKTLTEKTITLDVETSDsihnVKAKIQNKEGIPLDQQRLIFAGKQLEDGLTLADYNIQKESTLhLVLRL 75
Cdd:cd17062     9 LPGQGSKKKKITLETSLDITGSE----LREKIAEELGVPEDRIKLISNGKVLKDEKTLAEQGVKNNSQV-MVLVL 78

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 36.94 E-value: 2.19e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 165 KNFTSDTLTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGI 222
Cdd:cd01809     6 KTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVL--QDDKKLKEYDV 61

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 37.26 E-value: 3.15e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063710493 330 RINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGC-TLADYSIQKESTLHLV 390
Cdd:cd01795     7 RKSLTVSSTTTLKELKLQIMEKFSVAPFD--QHLYFNGRELTDDSaTLADLGILPGDVLYLK 66

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

Pssm-ID: 340494 [Multi-domain] Cd Length: 73 Bit Score: 36.77 E-value: 3.22e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063710493 319 MQIFVKTLTRKRI-NLEVESWDTIENVKAMVQDKEGIqpQPNLQRLIFLGKELK-DGCTLADYSIQ 382
Cdd:cd01796     1 MKLTVTTEDDDRLfSLEVSPDMTLEDLKALCEAETGI--PAAEQVLLHNGQPLTdDKKTLEALGLK 64

ubiquitin-like (Ubl) domain found in midnolin and similar proteins; Midnolin, also termed midbrain nucleolar protein, is a nucleolar protein that may be involved in regulation of genes related to neurogenesis in the nucleolus. It is strongly expressed at the mesencephalon (midbrain) of the embryo in day 12.5 (E12.5) mice and its expression is developmentally regulated. Midnolin plays a role in cellular signaling of adult tissues and regulates glucokinase enzyme activity in pancreatic beta cells. It can also control development via regulation of mRNA transport in cells. Midnolin contains an N-terminal conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340502 Cd Length: 70 Bit Score: 36.47 E-value: 3.22e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 407 LEVLSSDTIKSVKAKIQDKVGSPPDQQILLFRGGQLQDGrTLGDYNIRNESTLHL 461
Cdd:cd01804    15 LSVPPNETVEGLKRRISKKLKVPKERITLLHKEKQLKDG-TLRENGIGDGSKLTL 68

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

Pssm-ID: 340493 [Multi-domain] Cd Length: 99 Bit Score: 37.26 E-value: 3.48e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493 251 TGENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGR-TLAHYNIQKGSTLYLV 312
Cdd:cd01795     4 RGERKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELTDDSaTLADLGILPGDVLYLK 66

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

Pssm-ID: 340490 Cd Length: 75 Bit Score: 36.75 E-value: 3.62e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIF--LGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd01792     1 WDLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQ--QRLAVqpSGVELQDGVRLASQGLGPSSTVLLVV 73

ubiquitin-like (Ubl) domain found in small nuclear ribonucleoprotein U11/U12 subunit 25 (SNRNP25) and similar proteins; SNRNP25, also termed U11/U12 small nuclear ribonucleoprotein 25 kDa protein, U11/U12 snRNP 25 kDa protein (U11/U12-25K), or minus-99 protein, is a component of the U11/U12 snRNPs that are part of the U12-type spliceosome. It contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

Pssm-ID: 340578 Cd Length: 89 Bit Score: 37.11 E-value: 3.63e-03

                          10        20
                  ....*....|....*....|....*...
gi 1063710493 202 LIFHGEELfTEDNRTLADYGIRNRSTLC 229
Cdd:cd17058    59 LCFDGQKL-TDDKAKLKDYGIRNGDELT 85

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog A (HR23A); HR23A, also termed RAD23A, is a DNA repair protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation, which is required for efficient nucleotide excision repair (NER), a primary mechanism for removing UV-induced DNA lesions. HR23A also plays a critical role in the interaction of HIV-1 viral protein R (Vpr) with the proteasome, especially facilitating Vpr to promote protein poly-ubiquitination. HR23A contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340646 Cd Length: 76 Bit Score: 36.57 E-value: 4.22e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQP-NLQRLIFLGKELKDGCTLADYSIQKES 385
Cdd:cd17126     1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPvAGQKLIYAGKILSDDVPIRDYRIDEKN 68

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), which may function in the regulation of cell cycle progression. NUB1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

Pssm-ID: 340582 Cd Length: 78 Bit Score: 36.35 E-value: 4.89e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063710493 488 ITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVGSRTLLDYNIQKGSTI 542
Cdd:cd17062    19 ITLETSLDITGSELREKIAEELGVPEDRIKLISNGKVLKDEKTLAEQGVKNNSQV 73

ubiquitin-like (Ubl) domain found in non-canonical Inhibitor of kappa B kinases IKKepsilon and TBK1, and similar proteins; IKKepsilon and TBK1 (TRAF family member-associated NF-kappaB activator-binding kinase 1) are non-canonical members of IKK family. They have been characterized as activators of nuclear factor-kappaB (NF-kappaB), but they are not essential for NF-kappaB activation. They play critical roles in antiviral response via phosphorylation and activation of transcription factors IRF3, IRF7, STAT1 and STAT3. They are also involved in the survival, tumorigenesis and development of various cancers. Both IKKepsilon and TBK1 contain an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

Pssm-ID: 340518 Cd Length: 77 Bit Score: 36.06 E-value: 5.56e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1063710493 172 LTLKVESSDTIENVKAKIQDREGLRPDHQRLIFHGEELFTEDNRTLADY 220
Cdd:cd12219    15 LKIYLDPTETLAEFQELIAEQTEIPAKNQLLLFEGQLLEEEVTLPVSDY 63

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

Pssm-ID: 340642 Cd Length: 74 Bit Score: 36.00 E-value: 5.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710493 155 MQIFVSTFSGKnftsDTLTLKVESSDT-IENVKAKIQDREGLRPDHQRLIFHGEELftEDNRTLADYGIRNRSTLCLALR 233
Cdd:cd17122     1 MWIQVRTMDGK----ETHRIDSLSKLTkVEELRQKIQELFGVEPERQRLFYRGKQM--EDGHTLFDYSVGLNDIVQLLVR 74

ubiquitin-like (Ubl) domain found in transmembrane and ubiquitin-like domain-containing proteins TMUB1, TMUB2, and similar proteins; TMUB1, also termed dendritic cell-derived ubiquitin-like protein (DULP), or hepatocyte odd protein shuttling protein, or ubiquitin-like protein SB144, or HOPS, is highly expressed in the nervous system. It is involved in the termination of liver regeneration and plays a negative role in interleukin-6-induced hepatocyte proliferation. The overexpression of Tmub1 has been shown to play a role in the inhibition of cell proliferation. TMUB1 has been implicated in the regulation of locomotor activity and wakefulness in mice, perhaps acting through its interaction with CAMLG. It also facilitates the recycling of AMPA receptors into synaptic membrane in cultured primary neurons. TMUB1 contains transmembrane domains and a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. TMUB2 is an uncharacterized transmembrane domain and Ubl domain-containing protein that shows high sequence similarity to TMUB1.

Pssm-ID: 340577 Cd Length: 74 Bit Score: 36.05 E-value: 5.97e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063710493  90 TITLEVK-SSDTIDNVKAKIQDKEGILPRQQ-----------RLIFAGKQL-EDGRTLADYNIQKESTLHLVLR 150
Cdd:cd17057     1 TITIRLKfLNETERVVYARPEDTVGDFKRRHfpdelaqgkrvRLIYQGQLLrDDSRTLSSYGIQDGSVIHCHIS 74

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340497 Cd Length: 81 Bit Score: 36.04 E-value: 6.44e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063710493  14 TITLDVETSDSIHNVKAKIQNKEGIPLDQQRLIFaGKQL-EDGLTLADYNIQKEST---LHLV 72
Cdd:cd01799    18 PITLKVRPHTTIASLKRQIFLEYGFPPSVQRWII-GKRLaTDDETLLSYGIKDSGDpafLYLV 79

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

Pssm-ID: 340543 Cd Length: 78 Bit Score: 35.86 E-value: 6.44e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063710493 319 MQIFVKTLTRKRINLEVESWDTIENVKAMVQDKEGIQPQPNL-QRLIFLGKELKDGCTLADYSIQKES 385
Cdd:cd16126     1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAgQKLIYAGKILNDDTALKEYKIDEKN 68

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

Pssm-ID: 340584 [Multi-domain] Cd Length: 72 Bit Score: 35.89 E-value: 6.61e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063710493 155 MQIFVSTFSGKNftsdtLTLKVESSDTIENVKAKIQDREGLRPDHQ-RLIFHGEELftEDNRTLADYGIRNRSTLCL 230
Cdd:cd17064     1 MKVIVKSLGGKG-----SLLRVDASETLESLKGKASKKLDDKPSEKvKLFYSGKEL--EDGKSLAEQNVPPNSLVHL 70

ubiquitin-like (Ubl) domain found in BAG family molecular chaperone regulator 1 (BAG1) and similar proteins; BAG1, also termed Bcl-2-associated athanogene 1, or HAP, is a multifunctional protein involved in a variety of cellular functions such as apoptosis, transcription, and proliferative pathways, as well as in cell signaling and differentiation. It delivers chaperone-recognized unfolded substrates to the proteasome for degradation. BAG1 functions as a co-chaperone for Hsp70/Hsc70 to increase Hsp70 foldase activity. It also suppresses apoptosis and enhances neuronal differentiation. As an anti-apoptotic factor, BAG1 interacts with tau and regulates its proteasomal degradation. It also binds to BCR-ABL with a high affinity, and directly routes immature BCR-ABL for proteasomal degradation. It acts as a potential therapeutic target in Parkinson's disease. It also modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution, suggesting a role in Huntington's disease. There are at least four isoforms of Bag1 protein that are formed by alternative initiation of translation within a common mRNA. BAG1 contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and a C-terminal BAG domain.

Pssm-ID: 340510 [Multi-domain] Cd Length: 77 Bit Score: 35.71 E-value: 6.83e-03

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gi 1063710493 488 ITLEVESSDTIDNVKVKIQHKVGIPLDRQRLIFGGRVLVG-SRTLLDYNIQKGSTI 542
Cdd:cd01812    16 LPSQDEDEPTLQDLAEAIEEVTGVPVENQKLIFKGKSLKDpEQPLSALGVKNGSKI 71

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

Pssm-ID: 340506 [Multi-domain] Cd Length: 73 Bit Score: 35.68 E-value: 6.93e-03

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gi 1063710493 321 IFVKTLTRKRiNLEVESWDTIENVKAMVQDKEGiQPQPNLQrLIFLGKELKDGCTLADYSIQKESTLHLV 390
Cdd:cd01808     5 VTVKTPKEKE-DFEVPEDSSVKEFKEEISKKFK-APVEQLV-LIFAGKILKDQDTLSQHGIKDGLTVHLV 71

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

Pssm-ID: 340572 [Multi-domain] Cd Length: 74 Bit Score: 35.71 E-value: 7.38e-03

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gi 1063710493 329 KRINLEVESWDTIENVKAMVQDKEGIQPQPnlQRLIFLGKELKDGCTLADYSIQKESTLHLVL 391
Cdd:cd17052    10 DLMTFDANPQDSVKKINEHVRSKTKVPVQD--QVLLLGSKILKPRRRLSSYGIDKEKTIHLTL 70

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

Pssm-ID: 340497 Cd Length: 81 Bit Score: 35.65 E-value: 8.64e-03

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gi 1063710493 552 MQIFI--KTLTGKTIILEVESSDTIANVKEKIQVKEGIKPDQQMLIfFGQQL-EDGVTLGDYDIHK-KSTLYLVL 622
Cdd:cd01799     5 IKVYVedKSSSSGPITLKVRPHTTIASLKRQIFLEYGFPPSVQRWI-IGKRLaTDDETLLSYGIKDsGDPAFLYL 78

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

Pssm-ID: 340507 [Multi-domain] Cd Length: 71 Bit Score: 35.40 E-value: 9.12e-03

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gi 1063710493 252 GENFILEVESSDTIDNVKAKLQDKERIPMDLHRLIFAGKPLEGGRTLAHYNIQkGSTLYLVTR 314
Cdd:cd01809    10 SQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVD-GKVIHLVER 71