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 19920714 183 LYSGSLTAAREFATKRQRWLLVNVQDEN-FQSQTLNRDVWSDKELKKLIRRQFTFWQVDNDTSEGRRFVAFYHCATLPYI 261
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDeFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 19920714 262 CVIDPRTGEEVWRSAEPK-LENILPDLRQFLKEH 294
Cdd:cd02958  81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

UBA-like domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 19920714     8 DALVEQVREVTACSMDEAKYYLSACANDVSAAVALFFEQAAST 50
Cdd:pfam14555   1 DELIAQFQAITGADEEVARQYLEAHNWDLEAAVNAFFDDGEAS 43

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 19920714 183 LYSGSLTAAREFATKRQRWLLVNVQDEN-FQSQTLNRDVWSDKELKKLIRRQFTFWQVDNDTSEGRRFVAFYHCATLPYI 261
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDeFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 19920714 262 CVIDPRTGEEVWRSAEPK-LENILPDLRQFLKEH 294
Cdd:cd02958  81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

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 19920714 414 LKLRLLNaagtDEMVQLRWPSDTKLQTLRLYISQTHKHIPQDgYKLICAFPRKFLEAEHNDSSLKELGLHPSANLHLT 491
Cdd:cd01767   2 IQIRLPD----GSRIQRRFSKSDTLQDLYDFVESNLGDSPSS-FSLVTSFPRRVLTDEDSDKTLEELGLTPNAVLFVE 74

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19920714   429 QLRWPSDTKLQTLRLYISQtHKHIPQDGYKLICAFPRKFLEAEHNDSSLKELGLHPSANL 488
Cdd:pfam00789  18 VRRFNSSDKLQTVYDFVDS-NRYDDLEPFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTL 76

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 19920714   8 DALVEQVREVTACSMDEAKYYLSACANDVSAAVALFFEQ 46
Cdd:cd14348   1 DELIAQFVSVTGADEDRAKFFLESAGWDLEAALSSFFES 39

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 19920714 183 LYSGSLTAAREFATKRQRWLLVNVQDEN-FQSQTLNRDVWSDKELKKLIRRQFTFWQVDNDTSEGRRFVAFYHCATLPYI 261
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDeFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 19920714 262 CVIDPRTGEEVWRSAEPK-LENILPDLRQFLKEH 294
Cdd:cd02958  81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

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 19920714 414 LKLRLLNaagtDEMVQLRWPSDTKLQTLRLYISQTHKHIPQDgYKLICAFPRKFLEAEHNDSSLKELGLHPSANLHLT 491
Cdd:cd01767   2 IQIRLPD----GSRIQRRFSKSDTLQDLYDFVESNLGDSPSS-FSLVTSFPRRVLTDEDSDKTLEELGLTPNAVLFVE 74

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19920714 408 KTELTALKLRLlnaaGTDEMVQLRWPSDTKLQTLRLYISQthKHIPQDGYKLICAFPRKFLEAEHNDSSLKELGLHPSAN 487
Cdd:cd01771   1 TEPISKLRFRL----PGGEFLTRRFLASEPLQVLLNFVAS--KGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQET 74

                ...
gi 19920714 488 LHL 490
Cdd:cd01771  75 LFL 77

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 19920714 412 TALKLRLLNAAGTDEMVQLRWPsdtkLQTLRLYIsQTHKHIPQDGYKLICAFPRKFLEAEHNDSSLKELGLHPSANLHLT 491
Cdd:cd01772   7 CRLQVRLTNGSTLTQTFGAKEQ----LAAVRLYV-ELNRTDGDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSAVLIVT 81

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 19920714 433 PSDTkLQTLRLYISQtHKHIPQDGYKLICAFPRKFLEaeHNDSSLKELGLHPSANLHL 490
Cdd:cd17077  22 FSDT-IGDLRRYLDK-HRSKDAASYEIVTTFPNKVYD--DDSATLEELGLVPNATLHL 75

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 19920714 429 QLRWPSDTKLQTLRLYISQthKHIPQDGYKLICAFPRKFLEAEHNDSSLKELGLHPS 485
Cdd:cd01773  15 QLSLPASAKLKALVKYVSS--KGYPNERYELVTNFPRRKLSHLDYDITLKEAGLCPQ 69

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 19920714   9 ALVEQVREVTACSMDEAKYYLSACANDVSAAVALFFE 45
Cdd:cd14345   1 ALIEQFTSITGADDTVARHMLEACNGNLEMAVNMHLD 37

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 19920714  16 EVTACSMDEAKYYLSACANDVSAAVALFF 44
Cdd:cd14273   3 EITGADPETARQYLESNNWDLEAAINLYF 31