UAS family, FAS-associated factor 1 (FAF1) subfamily; FAF1 contains a UAS domain of unknown function N-terminal to a ubiquitin-associated UBX domain. FAF1 also contains ubiquitin-associated UBA and nuclear targeting domains, N-terminal to the UAS domain. 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. It 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-kB (NF-kB) by interfering with the nuclear translocation of the p65 subunit. FAF1 also interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 339 YFIGSLEAAFQEAFYGKARDRKLLAIYLHHDESVLTNVFCSQMLCAESIVSYLSQNFITWAWDMTKEANRARFLTMCTRH 418
Cdd:cd02990     1 FFIGSLEAAFQEACYRKARDRKLLAIYLHHDESVLSNVFCSQLLCAESIVQYLSQNFITWGWDMTKESNKARFLSSCTRH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 419 FGSVVAQTIRTQKTDQFPLFLIIMGKRSSNEVLNVIQGNTTVDELMMRLMAAMEIF 474
Cdd:cd02990    81 FGSVAAQTIRNIKTDQLPAILIIMGKRSSNEVLNVIQGNTGVDELLMRLIEAMEMF 136

ubiquitin-like (Ubl) domain 2 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 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 second Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 180 NFMLIITHREVQREYNLNFSGSSTIQEVKRNVYDLTSIPVRHQLWEGWPPSATDDSMTLAVsGVSFPCHRLTVGRR 255
Cdd:cd17130     1 NYTLNITDTTSQREYNLNFPGSKTIQEVKQDVSDLTSIPVRHQRWTGWPSGASDDTMLLAL-GLDFPCHRLTVSRR 75

UBA-like domain found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also called UBX domain-containing protein 12 or UBX domain-containing protein 3A, is a multi-functional Fas associating protein that contains an N-terminal ubiquitin-associated (UBA)-like domain, UAS and ubiquitin-like (UBX) domains, p150 subunit of a chromatin assembly factor like domain (CAF) and a novel nuclear localization signal (NLS). 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.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 2024516180   1 MLACTGIENIDEAITLLEQNNWDLVAAINGVIP 33
Cdd:cd14413     1 FQACTGIEDIDECIMLLEQNNWNLVAAVNAVIP 33

UAS family, FAS-associated factor 1 (FAF1) subfamily; FAF1 contains a UAS domain of unknown function N-terminal to a ubiquitin-associated UBX domain. FAF1 also contains ubiquitin-associated UBA and nuclear targeting domains, N-terminal to the UAS domain. 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. It 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-kB (NF-kB) by interfering with the nuclear translocation of the p65 subunit. FAF1 also interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 339 YFIGSLEAAFQEAFYGKARDRKLLAIYLHHDESVLTNVFCSQMLCAESIVSYLSQNFITWAWDMTKEANRARFLTMCTRH 418
Cdd:cd02990     1 FFIGSLEAAFQEACYRKARDRKLLAIYLHHDESVLSNVFCSQLLCAESIVQYLSQNFITWGWDMTKESNKARFLSSCTRH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 419 FGSVVAQTIRTQKTDQFPLFLIIMGKRSSNEVLNVIQGNTTVDELMMRLMAAMEIF 474
Cdd:cd02990    81 FGSVAAQTIRNIKTDQLPAILIIMGKRSSNEVLNVIQGNTGVDELLMRLIEAMEMF 136

ubiquitin-like (Ubl) domain 2 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 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 second Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 180 NFMLIITHREVQREYNLNFSGSSTIQEVKRNVYDLTSIPVRHQLWEGWPPSATDDSMTLAVsGVSFPCHRLTVGRR 255
Cdd:cd17130     1 NYTLNITDTTSQREYNLNFPGSKTIQEVKQDVSDLTSIPVRHQRWTGWPSGASDDTMLLAL-GLDFPCHRLTVSRR 75

UAS domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180  326 AEFSSRYGdchPVYFIGSLEAAFQEAFygkaRDRKLLAIYLHHDESVLTNVFCSQMLCAESIVSYLSQNFITWAWDMTKE 405
Cdd:smart00594   1 KLFRPPYG---PLFYQGSLEAAKQEAS----RQRRLLWLYLHSQDSPDSQVFNRDVLCNEAVKSLIRENFIFWQVDVDTS 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024516180  406 ANRARFLTMctrhfgsvvaqtirtqKTDQFPLFLIIMGKR--SSNEVLNVIQGNTTVDELMMRLM 468
Cdd:smart00594  74 EGQRVSQFY----------------KLDSFPYVAIVDPRTgqRVIEWVGVVEGEISPEELMTFLE 122

Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024516180  560 VSKLRIRTPSGEFFERRFLASSKLQVVFDFV-ASKGYPWEEYKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLEA 635
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVsAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELALLPSSTLVLEP 77

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 477 QQQEDIKDEDEREARENVKrEQDEAYRislEADRAKREAQEREMAEQfrLEQIRKEQEEEREAIRLSLEQSLPPEPKEES 556
Cdd:pfam09731 301 KKLAELKKREEKHIERALE-KQKEELD---KLAEELSARLEEVRAAD--EAQLRLEFEREREEIRESYEEKLRTELERQA 374

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2024516180 557 TESVSKLR--IRTPSGEfFERRFLASSKLQV 585
Cdd:pfam09731 375 EAHEEHLKdvLVEQEIE-LQREFLQDIKEKV 404

Archaeal/vacuolar-type H+-ATPase subunit H [Energy production and conversion]; Archaeal/vacuolar-type H+-ATPase subunit H is part of the Pathway/BioSystem: A/V-type ATP synthase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024516180 464 MMRLMAAMEIFSAQQQ-EDIKDEDEREARENVKREQDEAYRIsleADRAKREAQEremAEQFRLEQIRKEQEEEREAIR 541
Cdd:COG2811     1 MDRPEVLKEIKEAEEEaDEIIEEAKEEREERIAEAREEAEEI---IEQAEEEAEE---EAQERLEEAREEAEAEAEEII 73

polyubiquitin binding domain of NEMO and related proteins; NEMO (NF-kappaB essential modulator) is a regulatory subunit of the kinase complex IKK, which is involved in the activation of NF-kappaB via phosporylation of inhibitory IkappaBs. This mechanism requires the binding of NEMO to ubiquinated substrates. Binding is achieved via the UBAN motif (ubiquitin binding in ABIN and NEMO), which is described in this model. This region of NEMO has also been named CoZi (for coiled-coil 2 and leucine zipper). ABINs (A20-binding inhibitors of NF-kappaB) are sensors for ubiquitin that are involved in regulation of apoptosis, ABIN-1 is presumed to inhibit signalling via the NF-kappaB route. The UBAN motif is also found in optineurin, the product of a gene associated with glaucoma, which has been characterized as a negative regulator of NF-kappaB as well.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 460 VDELMMRLMAAMEIFSAQQQ--EDIKDEDE--REARENVK--REQDEAYRISLEADRAKRE--AQERE-MAEQfrLEQIR 530
Cdd:cd09803     3 IDELAARLQEAEEALALKQEdiDELKEEIAqqEADLETIPvlKAQAEIYKSDFEAERAAREklHQEKEqLAEQ--LEYLQ 80

                  ....*
gi 2024516180 531 KEQEE 535
Cdd:cd09803    81 RENQE 85

UAS family, FAS-associated factor 1 (FAF1) subfamily; FAF1 contains a UAS domain of unknown function N-terminal to a ubiquitin-associated UBX domain. FAF1 also contains ubiquitin-associated UBA and nuclear targeting domains, N-terminal to the UAS domain. 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. It 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-kB (NF-kB) by interfering with the nuclear translocation of the p65 subunit. FAF1 also interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 339 YFIGSLEAAFQEAFYGKARDRKLLAIYLHHDESVLTNVFCSQMLCAESIVSYLSQNFITWAWDMTKEANRARFLTMCTRH 418
Cdd:cd02990     1 FFIGSLEAAFQEACYRKARDRKLLAIYLHHDESVLSNVFCSQLLCAESIVQYLSQNFITWGWDMTKESNKARFLSSCTRH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 419 FGSVVAQTIRTQKTDQFPLFLIIMGKRSSNEVLNVIQGNTTVDELMMRLMAAMEIF 474
Cdd:cd02990    81 FGSVAAQTIRNIKTDQLPAILIIMGKRSSNEVLNVIQGNTGVDELLMRLIEAMEMF 136

ubiquitin-like (Ubl) domain 2 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 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 second Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 180 NFMLIITHREVQREYNLNFSGSSTIQEVKRNVYDLTSIPVRHQLWEGWPPSATDDSMTLAVsGVSFPCHRLTVGRR 255
Cdd:cd17130     1 NYTLNITDTTSQREYNLNFPGSKTIQEVKQDVSDLTSIPVRHQRWTGWPSGASDDTMLLAL-GLDFPCHRLTVSRR 75

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024516180  88 MLDFRVEYRDRNVDVVLEDSSTVGDIKHILENELQIPASKMLLKGWKTGDVDDSTVLKTLHLPKNNSLYVLTP 160
Cdd:cd17129     1 MLTFNVEYRDRTIDVVLPDTETVGDIKQILENELGIPPCKQILKGWKARTVSDSTVLRSLHLPKENSLYLLTP 73

UAS domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180  326 AEFSSRYGdchPVYFIGSLEAAFQEAFygkaRDRKLLAIYLHHDESVLTNVFCSQMLCAESIVSYLSQNFITWAWDMTKE 405
Cdd:smart00594   1 KLFRPPYG---PLFYQGSLEAAKQEAS----RQRRLLWLYLHSQDSPDSQVFNRDVLCNEAVKSLIRENFIFWQVDVDTS 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024516180  406 ANRARFLTMctrhfgsvvaqtirtqKTDQFPLFLIIMGKR--SSNEVLNVIQGNTTVDELMMRLM 468
Cdd:smart00594  74 EGQRVSQFY----------------KLDSFPYVAIVDPRTgqRVIEWVGVVEGEISPEELMTFLE 122

Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024516180  560 VSKLRIRTPSGEFFERRFLASSKLQVVFDFV-ASKGYPWEEYKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLEA 635
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVsAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELALLPSSTLVLEP 77

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 7 (UBXN7) and similar proteins; UBXN7, also termed UBX domain-containing protein 7 (UBXD7), belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN7 functions as a ubiquitin-binding adaptor that mediates the interaction between the AAA+ ATPase p97 (also known as VCP or Cdc48) and the transcription factor HIF1-alpha. It binds only to the active, NEDD8- or Rub1-modified form of cullins. In addition to having a UBX domain, UBXD7 contains a ubiquitin-associated (UBA), ubiquitin-associating (UAS), and ubiquitin-interacting motif (UIM) domains. Either UBA or UIM could serve as a docking site for neddylated-cullins. UBA domain is required for binding ubiquitylated-protein substrates, while the UIM motif is responsible for the binding to cullin RING ligases (CRLs), and the UBX domain is essential for p97 binding.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024516180 561 SKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEEYKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLEA 635
Cdd:cd01773     2 SKLMLRFPDGKREQLSLPASAKLKALVKYVSSKGYPNERYELVTNFPRRKLSHLDYDITLKEAGLCPQETIFVQE 76

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 8 (UBXN8) and similar proteins; UBXN8, also termed reproduction 8 protein (Rep8), or UBX domain-containing protein 6 (UBXD6), or D8S2298E, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN8 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. UBXN8 is a transmembrane protein that localizes to the endoplasmic reticulum (ER) membrane with its UBX domain facing the cytoplasm. It facilitates efficient ER-associated degradation (ERAD) by tethering p97 to the ER membrane.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 559 SVSKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEEYKLLGTFPRRDVTQlDPNKSLLEVKLYPQETLFLE 634
Cdd:cd01774     1 GAVTIALRFPGGRVHRRRFLTTENIQVLLDWMTKLGYHQTLYTLSTTYPRTILSD-DADKTLEDLGITKDVALNVE 75

UBA-like domain found in FAS-associated factor FAF1, FAF2 and similar proteins; FAF1, also called UBX domain-containing protein 12 or UBX domain-containing protein 3A, 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. FAF2, also called protein ETEA, UBX domain-containing protein 3B, or UBX domain-containing protein 8, is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. FAF2 shows homology to Fas-associated factor 1 (FAF1). Both of them contain N-terminal ubiquitin-associated (UBA)-like domain, UAS and ubiquitin-like (UBX) domains. Compared to FAF1, however, FAF2 lacks the nuclear targeting domain. The function of FAF2 remains unclear. A yeast two-hybrid assay showed that it can interact with Fas. Because of its homology to FAF1, it is postulated that FAF2 could be involved in modulating Fas-mediated apoptosis of T-cells and eosinophils of atopic dermatitis patients, making them more resistant to apoptosis.

                          10        20        30
                  ....*....|....*....|....*....|
gi 2024516180   3 ACTGIENIDEAITLLEQNNWDLVAAINGVI 32
Cdd:cd14353     3 SITGIEDSDQCRQILEAHNWDLEAAIQTAL 32

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; UBXN4, also termed ERAD (endoplasmic-reticulum-associated protein degradation) substrate erasing protein (erasin), or UBX domain-containing protein 2 (UBXD2), or UBXDC1, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN4 is an endoplasmic reticulum (ER) localized protein that interacts with p97 (also known as VCP or Cdc48) via its UBX domain. Erasin exists in a complex with other p97/VCP-associated factors involved in endoplasmic-reticulum-associated protein degradation (ERAD). p97 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 overexpression of UBXN4 increases degradation of a classical ERAD substrate and UBXN4 levels are increased in ER stressed cells. Anti-UBXN4 staining is increased in neuropathological lesions in brains of patients with Alzheimer's disease.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024516180 560 VSKLRIRTPSGEFFERRFLASSKLQVVFDFVASK-GYPWEEYKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFL 633
Cdd:cd16117     1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTvGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVV 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024516180 563 LRIRTPSGEFFERRFLASSKLQVVFDFVASK-GYPWEEYKLLgtfprRDVTQLDPNKSLLEVKLYPQETLFLE 634
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRiGLPPDVIRLL-----FNGQVLDDLMTAKQVGLEPGEELHFV 68

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 479 QEDIKDEDEReARENVKREQDEAYRISLEADRAKREAQEREMAEQFRL-EQIRKEQEEEREAirlSLEQSLPPEpkEEST 557
Cdd:pfam11600  42 KEEAKAEKER-AKEEARRKKEEEKELKEKERREKKEKDEKEKAEKLRLkEEKRKEKQEALEA---KLEEKRKKE--EEKR 115

                          90       100
                  ....*....|....*....|....*....
gi 2024516180 558 ESVSKLRIRTPSGEFfeRRFLASSKLQVV 586
Cdd:pfam11600 116 LKEEEKRIKAEKAEI--TRFLQKPKTQQA 142

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024516180 469 AAMEIFSAQQQEDIKDEDEREARENVKREQDEAYRISLEADRAKREAQEREMAEQfRLEQIRKEQEE 535
Cdd:pfam09756   9 AKLELKEAKRQQREAEEEEREEREKLEEKREEEYKEREEREEEAEKEKEEEERKQ-EEEQERKEQEE 74

Vacuolar (H+)-ATPase G subunit; This family represents vacuolar (H+)-ATPase G subunit from several bacterial and archaeal species. Subunit G is a component of the peripheral stalk of the ATPase complex

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024516180 476 AQQQEdikdEDEREARENVKREQDEAYRISLEAdrakrEAQEREMAEQFRlEQIRKEQEEEREAIR 541
Cdd:pfam16999  18 DQQIE----AARKEAEREVEAAEAEAARILREA-----EAKAKALQAEYR-QELAAETARIREEAR 73

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 462 ELMMRLMAAMEIFSAQQQEDIKDEDEREARENVK-----REQDEAYRISLEADRAKREAQEREMAEQFRLEQIRKEQEEE 536
Cdd:pfam13868 123 EKQRQLREEIDEFNEEQAEWKELEKEEEREEDERileylKEKAEREEEREAEREEIEEEKEREIARLRAQQEKAQDEKAE 202

                          90
                  ....*....|
gi 2024516180 537 REAIRLSLEQ 546
Cdd:pfam13868 203 RDELRAKLYQ 212

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 465 MRLMAAMEIFSAQQQEDIKDEDEREArenvKREQDEAYRISLEADRAKR------EAQER--EMAEQFRLEQIRKEQEEE 536
Cdd:pfam15709 412 LQLQAAQERARQQQEEFRRKLQELQR----KKQQEEAERAEAEKQRQKElemqlaEEQKRlmEMAEEERLEYQRQKQEAE 487

                          90
                  ....*....|
gi 2024516180 537 REAiRLSLEQ 546
Cdd:pfam15709 488 EKA-RLEAEE 496

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024516180 476 AQQQEdiKDEDEREARENVK-----REQDEAYRISLEADRAKREAQEREMAEQFRLEQIRKEQEEEREA 539
Cdd:pfam13868 190 RAQQE--KAQDEKAERDELRaklyqEEQERKERQKEREEAEKKARQRQELQQAREEQIELKERRLAEEA 256

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024516180  91 FRVEYRD-RNVDVVLEDSSTVGDIKHILENELQIPASKMLLKGWKTGdVDDSTVLKTLHLPKNNSLYVL 158
Cdd:cd17039     1 ITVKTLDgKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKE-LKDDKTLSDYGIKDGSTIHLV 68

Ubiquitin regulatory domain X (UBX) 2 found in UBX domain protein 9 (UBXN9, UBXD9, or ASPSCR1) and similar proteins; UBXN9, also termed tether containing UBX domain for GLUT4 (TUG), or alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1), or alveolar soft part sarcoma locus (ASPL), or renal papillary cell carcinoma protein 17 (RCC17), belongs to the UBXD family of proteins that contains two ubiquitin regulatory domains X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, UBXN9 contains an N-terminal ubiquitin-like (Ubl) domain. UBXN9 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. However, high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers; the extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers.UBXN9 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4, assembly of the Golgi apparatus. In addition to GLUT4, UBXN9 also controls vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. UBXN9 and its budding yeast ortholog, Ubx4p, are multifunctional proteins that share some, but not all functions. Yeast Ubx4p is important for endoplasmic reticulum-associated protein degradation (ERAD) but UBXN9 appears not to share this function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024516180 563 LRIRTPSGEFFERRFLASSKLQVVFDFV----ASKGYPWeeyKLLGTFPRRDVTqlDPNKSLLEVKLYP 627
Cdd:cd16118     3 IRVQFPDRLVLQAFFRPLETVRALYDFVkshlADPDLPF---YLYTTPPKRVLK--DKNKTLYQAGLVP 66

Uncharacterized membrane protein YqiK, contains Band7/PHB/SPFH domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 466 RLMAAMEIFSAQQQEDIKDEDEREARENVKREQDEAYRIsleadraKREAQER---------EMAEQFRLEQIRKEQEEE 536
Cdd:COG2268   232 REIETARIAEAEAELAKKKAEERREAETARAEAEAAYEI-------AEANAERevqrqleiaEREREIELQEKEAEREEA 304

                  ..
gi 2024516180 537 RE 538
Cdd:COG2268   305 EL 306

polyubiquitin binding domain of NEMO and related proteins; NEMO (NF-kappaB essential modulator) is a regulatory subunit of the kinase complex IKK, which is involved in the activation of NF-kappaB via phosporylation of inhibitory IkappaBs. This mechanism requires the binding of NEMO to ubiquinated substrates. Binding is achieved via the UBAN motif (ubiquitin binding in ABIN and NEMO), which is described in this model. This region of NEMO has also been named CoZi (for coiled-coil 2 and leucine zipper). ABINs (A20-binding inhibitors of NF-kappaB) are sensors for ubiquitin that are involved in regulation of apoptosis, ABIN-1 is presumed to inhibit signalling via the NF-kappaB route. The UBAN motif is also found in optineurin, the product of a gene associated with glaucoma, which has been characterized as a negative regulator of NF-kappaB as well.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024516180 460 VDELMMRLMAAMEIFSAQQQ--EDIKDEDE--REARENVK--REQDEAYRISLEADRAKRE--AQERE-MAEQfrLEQIR 530
Cdd:cd09803     3 IDELAARLQEAEEALALKQEdiDELKEEIAqqEADLETIPvlKAQAEIYKSDFEAERAAREklHQEKEqLAEQ--LEYLQ 80

                  ....*
gi 2024516180 531 KEQEE 535
Cdd:cd09803    81 RENQE 85

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2024516180 487 EREAREnvKREQDEAYRISLEADRAKR-EAQEREMAEQFRLEQIRKEQEEEREA 539
Cdd:pfam05672  28 EREEQE--RLEKEEEERLRKEELRRRAeEERARREEEARRLEEERRREEEERQR 79

UBA-like domain found in the NXF family of mRNA nuclear export factors and similar proteins; This family includes nuclear RNA export factors (NXF1/NXF2), FAS-associated factors (FAF1/2), tyrosyl-DNA phosphodiesterase 2 (TDP2), OTU domain-containing proteins (OTU7A/OTU7B), NSFL1 cofactor p47, defective in cullin neddylation protein 1 (DCN1)-like protein (DCNL1/DCNL2), yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. 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. FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. Its biological function remains unclear. TDP2 is a 5'-Tyr-DNA phosphodiesterase required for the efficient repair of topoisomerase II-induced DNA double strand breaks. OTU7A and OTU7B are zinc finger proteins that function as deubiquitinating enzymes. p47 is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. DCNL1 plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. The biological function of DCNL2 remains unclear. Yeast DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity.

                          10        20
                  ....*....|....*....|....*..
gi 2024516180   3 ACTGIeNIDEAITLLEQNNWDLVAAIN 29
Cdd:cd14273     3 EITGA-DPETARQYLESNNWDLEAAIN 28