Ubiquitin regulatory domain X (UBX) found in UBX domain protein 1 (UBXN1) and similar proteins; UBXN1, also termed SAPK substrate protein 1 (SAKS1), UBA/UBX 33.3 kDa protein (Y33K), or UBXD10, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (Ubl or UBX) domain that has a beta-grasp ubiquitin-like fold without the C-terminal double glycine motif. UBXN1 has been identified as a substrate for stress-activated protein kinases (SAPKs). It binds polyubiquitin and valosin-containing protein (VCP), suggesting a role as an adaptor that directs VCP to polyubiquitinated proteins facilitating its destruction by the proteasome. In addition, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and be involved in the Ub-proteasome proteolytic pathways. UBXN1 can also associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347 248 PRDYTETRIQVRLQDGSTLQETFNVKEQLSAVRVFIQM-KTGIESPFSLMTTFPRKLFAEDDYEKPLEVLGLVPSAVITM 326
Cdd:cd01772   1 KKEYDECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELnRTDGDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSAVLIV 80

                .
gi 21356347 327 T 327
Cdd:cd01772  81 T 81

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347   108 AAKTGHTKFSESEEEKKALTEEEKKAQLALIEEKLKQKRIEREEREKIEALQREKNRIKSGKDMTEAKRRMEELemKKIV 187
Cdd:PTZ00121 1415 AAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEA--KKKA 1492

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 21356347   188 EQRKREKDEEKAARDRVKAQIEADKA--ARKAREQKELGNAEPA 229
Cdd:PTZ00121 1493 EEAKKKADEAKKAAEAKKKADEAKKAeeAKKADEAKKAEEAKKA 1536

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 1 (UBXN1) and similar proteins; UBXN1, also termed SAPK substrate protein 1 (SAKS1), UBA/UBX 33.3 kDa protein (Y33K), or UBXD10, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (Ubl or UBX) domain that has a beta-grasp ubiquitin-like fold without the C-terminal double glycine motif. UBXN1 has been identified as a substrate for stress-activated protein kinases (SAPKs). It binds polyubiquitin and valosin-containing protein (VCP), suggesting a role as an adaptor that directs VCP to polyubiquitinated proteins facilitating its destruction by the proteasome. In addition, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and be involved in the Ub-proteasome proteolytic pathways. UBXN1 can also associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347 248 PRDYTETRIQVRLQDGSTLQETFNVKEQLSAVRVFIQM-KTGIESPFSLMTTFPRKLFAEDDYEKPLEVLGLVPSAVITM 326
Cdd:cd01772   1 KKEYDECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELnRTDGDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSAVLIV 80

                .
gi 21356347 327 T 327
Cdd:cd01772  81 T 81

UBA domain found in UBX domain-containing protein 1 (UBXN1) and similar proteins; UBXN1, also called SAPK substrate protein 1 (SAKS1) or UBA/UBX 33.3 kDa protein, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (UBX) domain. It binds polyubiquitin and valosin-containing protein (VCP), and has been identified as a substrate for stress-activated protein kinases (SAPKs). Moreover, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and may be involved in the Ub-proteasome proteolytic pathways. In addition, UBXN1 can associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21356347   2 SEVQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAHVDD 42
Cdd:cd14302   1 SELQTLIEMGFSRNRAEKALAKTGNQGVEAAMEWLLAHEDD 41

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 21356347     2 SEVQTLMDMGFPRERVEYALEVTsNKGVEPAMEWL 36
Cdd:pfam00627   4 EAIQRLVEMGFDREQVREALRAT-GNNVERAAEYL 37

Ubiquitin associated domain; Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 21356347      4 VQTLMDMGFPRERVEYALEVTSNKgVEPAMEWLL 37
Cdd:smart00165   5 IDQLLEMGFSREEALKALRAANGN-VERAAEYLL 37

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 1 (UBXN1) and similar proteins; UBXN1, also termed SAPK substrate protein 1 (SAKS1), UBA/UBX 33.3 kDa protein (Y33K), or UBXD10, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (Ubl or UBX) domain that has a beta-grasp ubiquitin-like fold without the C-terminal double glycine motif. UBXN1 has been identified as a substrate for stress-activated protein kinases (SAPKs). It binds polyubiquitin and valosin-containing protein (VCP), suggesting a role as an adaptor that directs VCP to polyubiquitinated proteins facilitating its destruction by the proteasome. In addition, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and be involved in the Ub-proteasome proteolytic pathways. UBXN1 can also associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347 248 PRDYTETRIQVRLQDGSTLQETFNVKEQLSAVRVFIQM-KTGIESPFSLMTTFPRKLFAEDDYEKPLEVLGLVPSAVITM 326
Cdd:cd01772   1 KKEYDECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELnRTDGDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSAVLIV 80

                .
gi 21356347 327 T 327
Cdd:cd01772  81 T 81

UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21356347   250 DYTETRIQVRLQDGSTLQETFNVKEQLSAVRVFI-QMKTGIESPFSLMTTFPRKLFAEDDYEKPLEVLGLVPSAVI 324
Cdd:pfam00789   1 AEDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVdSNRYDDLEPFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTL 76

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 21356347    253 ETRIQVRLQDGSTLQETFNVKEQLSAVRVFI-QMKTGIESPFSLMTTFPRKLFAEDDYEKPLEVLGLVPSAVITM 326
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVsAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELALLPSSTLVL 75

UBA1 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAHVDDP 43
Cdd:cd14385   5 LAQLLGMGFPEVRCKKALLATGNSDAEAAMNWLFEHMDDP 44

UBA1 domain found in Arabidopsis thaliana ubiquitin carboxyl-terminal hydrolase 14 (atUBP14) and similar proteins; atUBP14, also called deubiquitinating enzyme 14, TITAN-6 protein, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is related to the isopeptidase T class of deubiquitinating enzymes that recycle polyubiquitin chains following protein degradation. atUBP14 is essential for early plant development. It can disassemble multi-ubiquitin chains linked internally via epsilon-amino isopeptide bonds using Lys48 and can process some, but not all, translational fusions of ubiquitin linked via alpha-amino peptide bonds. atUBP14 contains two ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAHVDDP 43
Cdd:cd14295   5 VAQLMEMGFPKVRAEKALFFTQNKGLEEAMEWLEEHSEDA 44

UBA domain found in ubiquitin-associated and SH3 domain-containing protein B (UBS3B) and similar proteins; UBS3B, or Cbl-interacting protein p70, suppressor of T-cell receptor signaling 1 (Sts-1), T-cell ubiquitin ligand 2 (TULA-2), or tyrosine-protein phosphatase STS1/TULA2, is ubiquitously expressed in mammalian tissues in a variety of cell types. It exhibits high phosphatase activity, but demonstrates no proapoptotic activity. It negatively regulates the tyrosine kinase Zap-70 activation and T cell receptor (TCR) signaling pathways that modulate T cell activation. Moreover, UBS3B acts as a Cbl- and ubiquitin-interacting protein that inhibits endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 21356347   2 SEVQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAH 39
Cdd:cd14301   1 SALEVLLSMGFPKHRAEKALAATGGRSVQLASDWLLSH 38

UBA domain found in Arabidopsis thaliana E3 ubiquitin-protein ligase UPL1 (atUPL1), UPL2 (atUPL2) and similar proteins; The family includes two highly similar 405-kDa HECT E3 ubiquitin-protein ligases (UPLs), UPL1 and UPL2, from Arabidopsis thaliana. The HECT E3 UPL family plays a prominent role in the ubiquitination of plant proteins. The biological functions of UPL1 and UPL2 remain unclear. Both of them contain a ubiquitin-associated (UBA) domain and a C-terminal HECT domain. UBA domain may be involved in ubiquitin metabolism. HECT domain is necessary and sufficient for their E3 catalytic activity, but requires ATP, E1 and an E2 of the Arabidopsis UBC8 family to ubiquitinate proteins.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAH 39
Cdd:cd14327   3 VAQLVEMGFSRERAEEALRAVGTNSVELAMEWLFTN 38

UBA1 domain found in Saccharomyces cerevisiae ubiquitin carboxyl-terminal hydrolase 14 (scUBP14) and similar proteins; scUBP14, also called deubiquitinating enzyme 14, glucose-induced degradation protein 6, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is the yeast ortholog of human Isopeptidase T (USP5), a deubiquitinating enzyme known to bind the 29-linked polyubiquitin chains. scUBP14 has been identified as a K29-linked polyubiquitin binding protein as well. It is involved in K29-linked polyubiquitin metabolism by binding to the 29-linked Ub4 resin and serving as an internal positive control in budding yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAH 39
Cdd:cd14296   4 VSQLMSMGFSENAAKRALYYTGNSSVEAAMNWLFEH 39

UBA1 domain found in ubiquitin carboxyl-terminal hydrolase 5 (UBP5); UBP5, also called deubiquitinating enzyme 5, Isopeptidase T (IsoT), ubiquitin thioesterase 5, or ubiquitin-specific-processing protease 5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell. Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. ZnF domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin. This model corresponds to the UBA1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21356347   2 SEVQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAHVDDP 43
Cdd:cd14383   5 SVIIQLVEMGFPMDACRKAVYYTGNSGAEAAMNWVMSHMDDP 46

UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins; HUWE1, also called ARF-binding protein 1 (ARF-BP1), HECT, UBA and WWE domain-containing protein 1, homologous to E6AP carboxyl terminus homologs protein 9 (HectH9), large structure of UREB1 (LASU1), Mcl-1 ubiquitin ligase E3 (Mule), upstream regulatory element-binding protein 1 (URE-B1), or URE-binding protein 1, may function as a ubiquitin-protein ligase that involves in the ubiquitination cascade that targets specific substrate proteins in proteolysis. It can ubiquitylate DNA polymerase beta (Pol beta), the major BER DNA polymerase and modulates base excision repair (BER). HUWE1 also acts as a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF tumor suppressor in p53 regulation. Moreover, HUWE1 is both required and sufficient for the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involving in DNA damage-induced apoptosis. Furthermore, HUWE1 plays an important role in the regulation of Cdc6 stability after DNA damage. In addition, HUWE1 works as a partner of N-Myc oncoprotein in neural cells. It ubiquitinates N-Myc and primes it for proteasomal-mediated degradation. HUWE1 contains a ubiquitin-associated (UBA) domain, a WWE domain, and a Bcl-2 homology region 3 (BH3) domain at the N-terminus and a HECT domain at the C-terminus. WWE domain plays a role in the regulation of specific protein-protein interactions in a ubiquitin conjugation system. BH3 domain is responsible for the specific binding to Mcl-1. HECT domain involves in the inhibition of the transcriptional activity of p53 via a ubiquitin-dependent degradation pathway. It also controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 21356347   2 SEVQTLMDMGFPRERVEYALEVTSNkgVEPAMEWLLAH 39
Cdd:cd14288   4 AHLQQLMDMGFTREHALEALLHTST--LEQATEYLLTH 39

UBA2 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA2 domain.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 21356347   3 EVQTLMDMGFPRERVEYALEVTSNKgVEPAMEWLLAH 39
Cdd:cd14297   3 LVKQLVDMGFTEAQARKALRKTNNN-VERAVDWLFEG 38

UBA domain found in probable E3 ubiquitin-protein ligase HERC2 and similar proteins; HERC2, also called HECT domain and RCC1-like domain-containing protein 2, is a SUMO-regulated E3 ubiquitin ligase that plays an important role in the SUMO-dependent pathway which orchestrates the DNA double-strand break (DSB) response. Moreover, HERC2 functions as a RNF8 auxiliary factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. In addition to a ubiquitin-association (UBA) domain, HERC2 contains more than one RCC1-like domains (RLDs) and a C-terminal HECT E3 ubiquitin ligase domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21356347   4 VQTLMDMGFPRERVEYAL-EVTSNKGVEPAME----WLLAHVD 41
Cdd:cd14402   3 VQQLMEMGFPRKNVEFALkSLSGSSGGLPTPEalvaWLLEHPD 45

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 11 (UBXN11) and similar proteins; UBXN11, also termed colorectal tumor-associated antigen COA-1, or socius, or UBX domain-containing protein 5 (UBXD5), 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. UBXN11 may function 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. UBXN11 also acts as a novel interacting partner of Rnd proteins (Rnd1, Rnd2, and Rnd3/RhoE), new members of Rho family of small GTPases. It directly binds to Rnd GTPases through its C-terminal region, and further participates in disassembly of actin stress fibers. UBXN11 also binds directly to Galpha12 and Galpha13 through its N-terminal region. As a novel activator of the Galpha12 family, UBXN11 promotes the Galpha12-induced RhoA activation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21356347 254 TRIQVRLQDGSTlqeTFNVK----EQLSAVRVFI-QMKTGIESPFSLMTTFPRKLFAEDDyeKPLEVLGLVPSA 322
Cdd:cd17077   3 TTLRIKSENGEQ---TYILKmrfsDTIGDLRRYLdKHRSKDAASYEIVTTFPNKVYDDDS--ATLEELGLVPNA 71

UBA domain found in plant PNGase/UBA or UBX (PUB) domain-containing proteins; This family includes some uncharacterized hypothetical proteins found in plants. Although their biological function remain unclear, all family members contain an N-terminal ubiquitin-associated (UBA) domain and a C-terminal PUB domain. UBA domain, along with UBL (ubiquitin-like) domain, has been implicated in proteasomal degradation by associating with substrates destined for degradation as well as with subunits of the proteasome, thus regulating protein turnover. PUB domain functions as a p97 (also known as valosin-containing protein or VCP) adaptor by interacting with the D1 and/or D2 ATPase domains. The type II AAA+ ATPase p97 is involved in a variety of cellular processes such as the deglycosylation of ERAD substrates, membrane fusion, transcription factor activation and cell cycle regulation through differential binding to specific adaptor proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAHVDDP 43
Cdd:cd14290   7 LKELEAMGFPRARAVRALHHTGNTSVEAAVNWIVEHENDP 46

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 1 (FAF1, also known as UBXN3A) and similar proteins; UBX domain-containing protein 3A (UBXN3A),also termed UBX domain-containing protein 12 (UBXD12), or FAF1, 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. In addition, FAF1 contains two tandem ubiquitin-like (Ubl) domains, which shows high structural similarity with 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. This family corresponds to UBX domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21356347 254 TRIQVRLQDGSTLQETFNVKEQLSAVRVFIQMKTGIESPFSLMTTFPRKLFAEDDYEKPLEVLGLVP 320
Cdd:cd01771   5 SKLRFRLPGGEFLTRRFLASEPLQVLLNFVASKGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFP 71

UBA domain found in probable E3 ubiquitin-protein ligase HERC1, HERC2 and similar proteins; HERC1, also called HECT domain and RCC1-like domain-containing protein 1, p532, or p619, is an ubiquitously expressed giant protein involved in ubiquitin-dependent intracellular membrane trafficking through its interaction with vesicle coat proteins such as clathrin and ARF. Moreover, it has been identified as a tuberous sclerosis complex TSC2-interacting protein that may play a role in TSC-mTOR (mammalian target of rapamycin) pathway. HERC2, also called HECT domain and RCC1-like domain-containing protein 2, is a SUMO-regulated E3 ubiquitin ligase that plays an important role in the SUMO-dependent pathway which orchestrates the DNA double-strand break (DSB) response. Moreover, HERC2 functions as a RNF8 auxiliary factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. HERC1 and HERC2 are multi-domain proteins with different domain organizations. Both of them contain a ubiquitin-association (UBA) domain, more than one RCC1-like domains (RLDs) and a C-terminal HECT E3 ubiquitin ligase domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAME----WLLAH 39
Cdd:cd14331   1 IVQLMEMGFSRRQIEMAMQALGSESDAPNIEnlvnWLLEH 40

UBA1 domain found in ubiquitin carboxyl-terminal hydrolase 13 (UBP13); UBP13, also called deubiquitinating enzyme 13, Isopeptidase T-3 (isoT3), ubiquitin thioesterase 13, or ubiquitin-specific-processing protease 13, is an ortholog of UBP5 implicated in catalyzing hydrolysis of various ubiquitin (Ub)-chains. It contains a zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. Due to the non-activating catalysis for K63-polyubiquitin chains, UBP13 may function differently from USP5 in cellular deubiquitination processes. Moreover, the zinc finger (ZnF) domain of USP13 cannot bind to Ub. Its tandem UBA domains can bind with different types of diUb but preferentially with K63-linked.USP13 can also regulate the protein level of CD3delta in cells via its UBA domains. This model corresponds to the UBA1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21356347   2 SEVQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAHVDDP 43
Cdd:cd14384   5 SSVMQLAEMGFPLEACRKAVYYTGNMGAEVAFNWIIAHMEEP 46

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar proteins; UBXN2A, also termed UBX domain-containing protein 4 (UBXD4), 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. UBXN2A functions as a p97 (also known as VCP or Cdc48) adaptor protein facilitating the regulation of the cell surface number and stability of alpha3-containing neuronal nicotinic acetylcholine receptors (nAChRs). It also regulates nicotinic receptor degradation by modulating the E3 ligase activity of carboxyl terminus of Hsc70 interacting protein (CHIP) that is involved in the degradation of several disease-related proteins. In addition, UBXN2A is an important anticancer factor that contributes to p53 localization and activation as a host defense mechanism against cancerous growth. It acts as a potential mortalin inhibitor, as well as a potential chemotherapy sensitizer for clinical application. It binds to the oncoprotein mortalin-2 (mot-2), and further unsequesters p53 from mot-2 in the cytoplasm, resulting in translocation of p53 to the nucleus where p53 proteins activate their downstream biological effects, including apoptosis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 21356347 254 TRIQVRLQDGSTLQETFNVKEQLSAVRVFIQMKTGIE--SPFSLMTTFP 300
Cdd:cd17160   8 TNIQIWLADGRRIVQKFNLSHRISHVRDFVEKIQGSSmsVPFTLATSLP 56

UBA domain found in ubiquitin-associated domain-containing protein 2 (UBAC2) and similar proteins; UBAC2, also called phosphoglycerate dehydrogenase-like protein 1, is a ubiquitin-associated domain (UBA)-domain containing protein encoded by gene UBAC2 (or PHGDHL1), a risk gene for Behcet's disease (BD). It may play an important role in the development of BD through its transcriptional modulation. Members in this family contain an N-terminal rhomboid-like domain and a C-terminal UBA domain.

                        10        20
                ....*....|....*....|...
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSN 26
Cdd:cd14305   6 VQQLVDMGFSREDVLEALRQSNN 28

UBA domain found in ubiquitin-associated and SH3 domain-containing protein A (UBS3A) and similar proteins; UBS3A, also called Cbl-interacting protein 4 (CLIP4), suppressor of T-cell receptor signaling 2 (Sts-2), or T-cell ubiquitin ligand 1 (TULA-1), is a lymphoid protein only detected in thymus, spleen, and bone marrow. UBS3A exhibits extremely low phosphatase activity, but is capable of promoting T-cell apoptosis independent of either T cell receptor (TCR)/CD3-mediated signaling or caspase activity. It functions as a negative regulator of TCR signaling. UBS3A can also inhibit HIV-1 biogenesis through the binding of ATP-binding cassette protein family E member 1 (ABCE-1), a host factor of HIV-1 assembly. Moreover, UBS3A acts as the Cbl- and ubiquitin-interacting protein that can inhibit endocytosis and downregulation of ligand-activated epidermal growth factor receptor (EGFR) by impairing Cbl-induced ubiquitination, as well as inhibit clathrin-dependent endocytosis in general. This family also includes Arabidopsis thaliana ubiquitin carboxyl-terminal hydrolase 14 (atUBP14) and some uncharacterized AAA-type ATPase-like proteins found in plants.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKGVEPAMEWLLAH 39
Cdd:cd14300   1 LETLLAMGFPEDVARKALKATGGKSIEKATDWLLSH 36

UBA1 domain found in Kip1 ubiquitination-promoting complex protein 2 (KPC2) and similar proteins; KPC2, also called ubiquitin-associated domain-containing protein 1 (UBAC1), or glialblastoma cell differentiation-related protein 1, is one of two subunits of Kip1 ubiquitination-promoting complex (KPC), a novel E3 ubiquitin-protein ligase that also contains KPC1 subunit and regulates the ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p27 at G1 phase. KPC2 contains a ubiquitin-like (UBL) domain and two ubiquitin-associated (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 21356347   2 SEVQTLMDMGFPRERVEYALeVTSNKGVEPAMEWLLAH 39
Cdd:cd14303   4 EALKQLTEMGFPEARATKAL-LLNRMSPTQAMEWLLEH 40

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347   103 EVEYHAAKTGHTKFSESEEEKKAL---TEEEKKAQLAL---IEEKLKQKRIEREEREKIEALQREKNRIKSGKDMTEAKR 176
Cdd:PTZ00121 1346 EAAKAEAEAAADEAEAAEEKAEAAekkKEEAKKKADAAkkkAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKK 1425

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 21356347   177 RMEEL----EMKKIVEQRKREKDEEKAARDRVKAQiEADKAARKAREQKEL 223
Cdd:PTZ00121 1426 KAEEKkkadEAKKKAEEAKKADEAKKKAEEAKKAE-EAKKKAEEAKKADEA 1475

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347    87 KSLKCDECGKVLRDHTEVEYHAAKTGHTKFSESEEEKKALTEEEKKAqlalieEKLKQKRIEREEREKIEALQREKNRIK 166
Cdd:PTZ00121 1361 AAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKA------DELKKAAAAKKKADEAKKKAEEKKKAD 1434

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21356347   167 SGKDMTEAKRRMEELEmKKIVEQRKRE----KDEEKAARDRVKAQIE----ADKAARKAREQKE 222
Cdd:PTZ00121 1435 EAKKKAEEAKKADEAK-KKAEEAKKAEeakkKAEEAKKADEAKKKAEeakkADEAKKKAEEAKK 1497

UBA domain found in uncharacterized protein At3g58460 from Arabidopsis thaliana and its homologs from other plants; The uncharacterized protein At3g58460 from Arabidopsis thaliana is also known as rhomboid-like protein 15 which is encoded by RBL15 gene. Although the biological function of the family members remains unclear, they all contain an N-terminal rhomboid-like domain and a C-terminal ubiquitin-associated (UBA) domain.

                        10        20        30
                ....*....|....*....|....*....|...
gi 21356347   4 VQTLMDMGFPRERVEYALEVTsNKGVEPAMEWL 36
Cdd:cd14287   4 VQSLVAMGFEKHRARRALDAA-GGDINTAVEIL 35

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356347   118 ESEEEKKALTEEEKKAQLALIEEKLKQKRIEREEREKIEALQREKNRIKSGKDMTEAKR-RMEELEMKKIVEQRKREKDE 196
Cdd:PTZ00121 1662 KAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEElKKAEEENKIKAEEAKKEAEE 1741

                          90       100       110
                  ....*....|....*....|....*....|.
gi 21356347   197 EKAARDRVKAQIEADKAARKAREQKELGNAE 227
Cdd:PTZ00121 1742 DKKKAEEAKKDEEEKKKIAHLKKEEEKKAEE 1772

UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also called negative regulator of ubiquitin-like proteins 1, 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 three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif. This model corresponds to UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|...
gi 21356347   4 VQTLMDMGFPRERVEYALEVTSNKgVEPAMEWL 36
Cdd:cd14291   5 LQQLMEMGFSEAEARLALRACNGN-VERAVDYI 36