UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting 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. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673 149 MHKGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFPYV 228
Cdd:cd02958    1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 268839673 229 SILDPRTGQKLVEWHQLD-VSSFLDQVTGFLGEH 261
Cdd:cd02958   81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

UBA-like domain found in UBX domain-containing protein 7 (UBXD7) and similar proteins; UBXD7, also known as 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 HIF1alpha. It binds only to the active, NEDD8- or Rub1-modified form of cullins. UBXD7 contains the ubiquitin-associated (UBA), ubiquitin-associating (UAS), ubiquitin regulatory X (UBX), and ubiquitin-interacting motif (UIM) domains. Either UBA or UIM could serve as a docking site for neddylated-cullins. Moreover, UBA-like domain is required for binding ubiquitylated-protein substrates, UIM motif is responsible for the binding to cullin RING ligases (CRLs), and UBX domain is essential for p97 binding.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 268839673  16 LIQQFTAITGASESVGKHMLEACNNNLEMAVTMFLD 51
Cdd:cd14345    2 LIEQFTSITGADDTVARHMLEACNGNLEMAVNMHLD 37

UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting 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. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673 149 MHKGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFPYV 228
Cdd:cd02958    1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 268839673 229 SILDPRTGQKLVEWHQLD-VSSFLDQVTGFLGEH 261
Cdd:cd02958   81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

UAS domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673   140 DLFRPPI-DLMHKGSFETAKECGQMQ--NKWLMINIQNVQDfaCQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRY 216
Cdd:smart00594   1 KLFRPPYgPLFYQGSLEAAKQEASRQrrLLWLYLHSQDSPD--SQVFNRDVLCNEAVKSLIRENFIFWQVDVDTSEGQRV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 268839673   217 IQFYKLGDFPYVSILDPRTGQKLVEWHQLDVSSFLDQVTGFLGE 260
Cdd:smart00594  79 SQFYKLDSFPYVAIVDPRTGQRVIEWVGVVEGEISPEELMTFLE 122

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673  151 KGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGdFPYVSI 230
Cdd:pfam13899   3 LSDLEEALAAAAERGKPVLVDFGADWCFTCQVLERDFLSHEEVKAALAKNFVLLRLDWTSRDANITRAFDGQG-VPHIAF 81

                  ...
gi 268839673  231 LDP 233
Cdd:pfam13899  82 LDP 84

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 268839673   412 KAQLMLRYPDGKREQITLPEQAKLLALVKHV-QSKGYPNERFELLTNFPRRKLSHLDYDITLQEAGLCPQETVFVQE 487
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVsAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELALLPSSTLVLEP 77

UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting 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. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673 149 MHKGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFPYV 228
Cdd:cd02958    1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 268839673 229 SILDPRTGQKLVEWHQLD-VSSFLDQVTGFLGEH 261
Cdd:cd02958   81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

UAS domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673   140 DLFRPPI-DLMHKGSFETAKECGQMQ--NKWLMINIQNVQDfaCQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRY 216
Cdd:smart00594   1 KLFRPPYgPLFYQGSLEAAKQEASRQrrLLWLYLHSQDSPD--SQVFNRDVLCNEAVKSLIRENFIFWQVDVDTSEGQRV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 268839673   217 IQFYKLGDFPYVSILDPRTGQKLVEWHQLDVSSFLDQVTGFLGE 260
Cdd:smart00594  79 SQFYKLDSFPYVAIVDPRTGQRVIEWVGVVEGEISPEELMTFLE 122

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 268839673 411 PKAQLMLRYPDGKREQITLPEQAKLLALVKHVQSKGYPNERFELLTNFPRRKLSHLDYDITLQEAGLCPQETVFVQER 488
Cdd:cd01771    3 PISKLRFRLPGGEFLTRRFLASEPLQVLLNFVASKGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQETLFLEER 80

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 268839673  151 KGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGdFPYVSI 230
Cdd:pfam13899   3 LSDLEEALAAAAERGKPVLVDFGADWCFTCQVLERDFLSHEEVKAALAKNFVLLRLDWTSRDANITRAFDGQG-VPHIAF 81

                  ...
gi 268839673  231 LDP 233
Cdd:pfam13899  82 LDP 84

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 268839673   412 KAQLMLRYPDGKREQITLPEQAKLLALVKHV-QSKGYPNERFELLTNFPRRKLSHLDYDITLQEAGLCPQETVFVQE 487
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVsAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELALLPSSTLVLEP 77

UBA-like domain found in NSFL1 cofactor p47 and similar proteins; p47, also called UBX domain-containing protein 2C, 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. p47, together with p97, forms the p97-p47 complex that plays an important role in regulation of membrane fusion events. p47 contains an N-terminal ubiquitin-associated (UBA)-like domain, a central SEP (named after shp1, eyc and p47) domain, and a ubiquitin-like (UBX) domain. UBA-like domain is responsible for forming a highly stable complex with ubiquitin. SEP domain and UBX domain may involve in p47 trimerization or forms a stable complex with the p97 N-terminal domain.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 268839673  16 LIQQFTAITGASESVGKHMLEACNNNLEMAVTMFLDGG 53
Cdd:cd14348    3 LIAQFVSVTGADEDRAKFFLESAGWDLEAALSSFFESG 40

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 268839673 413 AQLMLRYPDGKREQITLPEQAKLLALVKHV-QSKGYPNERFELLTNFPRRKLSHLDYDITLQEAGLCPQETVFV 485
Cdd:cd16117    2 ARIQFRLPDGSSFTNQFPSDAPLEEARQFVaQTVGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVV 75

UBA-like domain found in yeast UBX domain-containing protein 1 (Ubx1) and similar proteins; Ubx1, also called suppressor of high-copy PP1 protein (Shp1), is the substrate-recruiting cofactor of AAA-adenosine triphosphatase Cdc48 in Saccharomyces cerevisiae. In concert with ubiquitin-like Atg8, Cdc48 and Ubx1 are involved in the regulation of autophagosome biogenesis. Ubx1 also functions as a regulator of phosphoprotein phosphatase 1 (PP1) with differential effects on glycogen metabolism, meiotic differentiation, and mitotic cell cycle progression. All family members contain an N-terminal ubiquitin-associated (UBA)-like domain.

                         10        20        30
                 ....*....|....*....|....*....|
gi 268839673  17 IQQFTAITGASESVGKHMLEACNNNLEMAV 46
Cdd:cd14351    4 IQQFMELTGASPEVAQQYLEEYGGDLNDAI 33

UBA-like domain found in Saccharomyces cerevisiae UBX domain-containing protein 5 (Ubx5) and similar proteins; Ubx5 is a ubiquitin regulatory X (UBX) domain-containing protein encoded by the open reading frame (ORF) YDR330W in yeast. As the yeast ortholog of mammalian UBXD7, Ubx5 functions as the cofactor of AAA+ ATPase p97, also known as VCP or Cdc48. It binds only to the active, NEDD8- or Rub1-modified form of cullins. Ubx5 contains the ubiquitin-associated (UBA), ubiquitin-associating (UAS), ubiquitin regulatory X (UBX) and ubiquitin-interacting motif (UIM) domains and its UIM domain is required to promote UV-dependent degradation of polyubiquitinated Rpb1.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 268839673  15 GLIQQFTAITGAS-ESVGKHMLEACNNNLEMAVTMFLD 51
Cdd:cd14346    2 EQISTFLAITGSEdAAVARQFLEMAGGDLETAVSLFFE 39

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 268839673 433 AKLLALVKHVQSKGYPNerFELLTNFPRRKLShlDYDITLQEAGLCPQETVFVQ 486
Cdd:cd17077   27 GDLRRYLDKHRSKDAAS--YEIVTTFPNKVYD--DDSATLEELGLVPNATLHLR 76

ubiquitin-like (Ubl) domain found in ubiquitin thioesterase OTU1 and similar proteins; OTU1 (EC 3.4.19.12), also termed YOD1, or DUBA-8, or HIV-1-induced protease 7 (HIN-7), or OTU domain-containing protein 2 (OTUD2), is a p97-associated deubiquitinylase that functions as a key player in endoplasmic reticulum-associated degradation (ERAD). Its deubiquitinylase activity is also required for negatively regulating cholera toxin A1 (CTA1) retro-translocation. OTU1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a C2H2-type zinc finger, and an OTU domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 268839673 414 QLMLRYPDGKREQITLPEQAKLLALVKHVQSK-GYPNERFELLTNFPRRKLSHLDYDITLQEAGLCPQETVFVQ 486
Cdd:cd17059    2 RLRVRSKGGQHVLSLLTDTSTVGELQDRIAALtGIPPSSQKILYGFPPKPLDLSDEEASLESLGIQSGDTLIVE 75