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 18394134 182 MFQGSFEQAKTTSSSQDKWLLVNLQSTTEFSSHMLNRDTWANDAVSQTIKANFIFWQVYDDTTEGRKVCTYYKLESIPVV 261
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 18394134 262 LVIDPTTGQRMRMWTGMVDPENLLEDLVPFMDG 294
Cdd:cd02958  81 AIIDPRTGEVLKVWSGNITPEDLLSQLIEFLEE 113

UBA-like domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 18394134    11 QRLVSSFLEIAvGQTAETARQFLQATSWKLEEAIQLFYIGNEG 53
Cdd:pfam14555   1 DELIAQFQAIT-GADEEVARQYLEAHNWDLEAAVNAFFDDGEA 42

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 18394134 182 MFQGSFEQAKTTSSSQDKWLLVNLQSTTEFSSHMLNRDTWANDAVSQTIKANFIFWQVYDDTTEGRKVCTYYKLESIPVV 261
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 18394134 262 LVIDPTTGQRMRMWTGMVDPENLLEDLVPFMDG 294
Cdd:cd02958  81 AIIDPRTGEVLKVWSGNITPEDLLSQLIEFLEE 113

Ubiquitin regulatory domain X (UBX) structurally similar to a beta-grasp ubiquitin-like fold; The UBXD family of proteins 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. Members in this family function as cofactors 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. Based on domain composition, UBXD proteins can be divided into two main groups, with and without ubiquitin-associated (UBA) domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18394134 391 RVGIRLPNGQRLQRNFLKTDTIQLLWSFCYSQLEESerKKPLKLTQAIPGESKTLEyESNLTLEQSG-VANSMI 463
Cdd:cd01767   1 RIQIRLPDGSRIQRRFSKSDTLQDLYDFVESNLGDS--PSSFSLVTSFPRRVLTDE-DSDKTLEELGlTPNAVL 71

UBA-like domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 18394134    11 QRLVSSFLEIAvGQTAETARQFLQATSWKLEEAIQLFYIGNEG 53
Cdd:pfam14555   1 DELIAQFQAIT-GADEEVARQYLEAHNWDLEAAVNAFFDDGEA 42

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        30
                ....*....|....*....|....*....|..
gi 18394134  17 FLEIaVGQTAETARQFLQATSWKLEEAIQLFY 48
Cdd:cd14273   1 FMEI-TGADPETARQYLESNNWDLEAAINLYF 31

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 18394134 182 MFQGSFEQAKTTSSSQDKWLLVNLQSTTEFSSHMLNRDTWANDAVSQTIKANFIFWQVYDDTTEGRKVCTYYKLESIPVV 261
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 18394134 262 LVIDPTTGQRMRMWTGMVDPENLLEDLVPFMDG 294
Cdd:cd02958  81 AIIDPRTGEVLKVWSGNITPEDLLSQLIEFLEE 113

Ubiquitin regulatory domain X (UBX) structurally similar to a beta-grasp ubiquitin-like fold; The UBXD family of proteins 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. Members in this family function as cofactors 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. Based on domain composition, UBXD proteins can be divided into two main groups, with and without ubiquitin-associated (UBA) domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18394134 391 RVGIRLPNGQRLQRNFLKTDTIQLLWSFCYSQLEESerKKPLKLTQAIPGESKTLEyESNLTLEQSG-VANSMI 463
Cdd:cd01767   1 RIQIRLPDGSRIQRRFSKSDTLQDLYDFVESNLGDS--PSSFSLVTSFPRRVLTDE-DSDKTLEELGlTPNAVL 71

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 2 (FAF2, also known as UBXN3B) and similar proteins; UBX domain-containing protein 3B (UBXN3B), also termed protein ETEA, or FAF2, or UBX domain-containing protein 8 (UBXD8), 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. FAF2 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 p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated the RNA-binding protein HuR from messenger ribonucleoprotein (mRNP). Moreover, 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. A yeast two-hybrid assay showed that FAF2 can interact with Fas.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18394134 390 CRVGIRLPNGQRLQRNFLKTDTIQLLWSFCYSQlEESerkkPLKL-------TQAIPGEsKTLEYESNLTLEQSGVANS 461
Cdd:cd16120   1 VKILFKLPNGTRLERRFLKSDSLKVLYDFVFSH-EDS----PDKFqlvtnfpRRVLPCQ-PTEEQPNPPTLEEAGLGKS 73

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18394134   389 QCRVGIRLPNGQRLQRNFLKTDTIQLLWSFCYSQLEESERkkPLKLTQAIP-------GESKTLE 446
Cdd:pfam00789   4 VTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDLE--PFSLNTPFPrrpltdlDYSKTLK 66

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 10 (UBXN10) and similar proteins; UBXN10, also termed UBX domain-containing protein 3 (UBXD3), 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. UBXN10 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. UBXN10 localizes to cilia in a p97-dependent manner, and both p97 and UBXN10 are required for ciliogenesis. Additionally, UBXN10 interacts with the intraflagellar transport B (IFT-B) and regulates anterograde transport into cilia.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18394134 393 GIRLPNGQRLQRNFLKTDTIQLLwsFCYSQLEESERKKPLKL-TQAIPgesKTLEYESNLTLEQSGVAN 460
Cdd:cd17076   6 AIRLPDGQRFQRFFRPSDTLQDV--LAFAESQSGLDLSNCIIeTNEVP---RRVFSDLSKTIAECGIQD 69

UBA-like domain found in protein FAM100B; The family corresponds to the uncharacterized protein FAM100B and its homologs mainly found in Metazoa. Although their biological roles remain unclear, all family members contain a ubiquitin-associated (UBA)-like domain that may be involved in the binding of ubiquitin.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 18394134  10 QQRLVSSFLeIAVGQTAETARQFLQATSWKLEEAIQLFY 48
Cdd:cd14343   1 EQVMINQFV-LAAGCAADQAKQLLQAAHWQFETALSAFF 38

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 18394134  13 LVSSFLEIaVGQTAETARQFLQATSWKLEEAIQLFY 48
Cdd:cd14348   3 LIAQFVSV-TGADEDRAKFFLESAGWDLEAALSSFF 37

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 18394134  13 LVSSFLEIAVGQTAETARQFLQATSWKLEEAIQLFY 48
Cdd:cd14346   3 QISTFLAITGSEDAAVARQFLEMAGGDLETAVSLFF 38

UBA-like domain found in DCN1-like protein DCNL1, DCNL2 and similar proteins; DCNL1 (defective in cullin neddylation protein 1-like protein 1), also called DCUN1 domain-containing protein 1, is encoded by squamous cell carcinoma-related oncogene SCCRO (DCUN1D1). It interacts with known cullin isoforms as well as ROC1, Ubc12 and CAND1, the components of the neddylation pathway. It 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. DCNL1 contains an N-terminal ubiquitin-associated (UBA)-like domain and a C-terminal cullin binding domain that binds to cullins and Rbx-1, components of an E3 ubiquitin ligase complex for neddylation. DCNL2 (defective in cullin neddylation protein 1-like protein 2), also called DCUN1 domain-containing protein 2, is encoded by gene DCUN1D2. Although its biological function remains unclear, DCNL2 shows high sequence similarity with DCNL1 and may also contribute to neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Like DCNL1, DCNL2 contains an N-terminal UBA-like domain and a C-terminal cullin binding domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 18394134   9 DQQRLVSSFLEIAvgQTAE-TARQFLQATSWKLEEAIQLFY 48
Cdd:cd14350   1 SQKDKVRQFMSIT--QANEkTAIQCLKDADWNLELAVDAYF 39