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 6320537  219 MSKLDLDAAKQKARAKQKWIMINIQDSGIFQCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNAQPYLQFYHlnnKDDL 298
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYK---VDKY 77

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6320537  299 PHIAILDPITGERVKQWNRVVPiPEQFISEINEFLASF 336
Cdd:cd02958  78 PHIAIIDPRTGEVLKVWSGNIT-PEDLLSQLIEFLEEF 114

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 6320537    3 EGKVDEFMAITGADDAAIATQFIEMADGNLNTAISLFFE 41
Cdd:cd14346   1 DEQISTFLAITGSEDAAVARQFLEMAGGDLETAVSLFFE 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 6320537  219 MSKLDLDAAKQKARAKQKWIMINIQDSGIFQCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNAQPYLQFYHlnnKDDL 298
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYK---VDKY 77

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6320537  299 PHIAILDPITGERVKQWNRVVPiPEQFISEINEFLASF 336
Cdd:cd02958  78 PHIAIIDPRTGEVLKVWSGNIT-PEDLLSQLIEFLEEF 114

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 6320537    223 DLDAAKQKARAKQKWIMINIQDSGIFQCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNAQPYLQFYHlnnkDDLPHIA 302
Cdd:pfam13899   5 DLEEALAAAAERGKPVLVDFGADWCFTCQVLERDFLSHEEVKAALAKNFVLLRLDWTSRDANITRAFDG----QGVPHIA 80

                  ....
gi 6320537    303 ILDP 306
Cdd:pfam13899  81 FLDP 84

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 6320537    3 EGKVDEFMAITGADDAAIATQFIEMADGNLNTAISLFFE 41
Cdd:cd14346   1 DEQISTFLAITGSEDAAVARQFLEMAGGDLETAVSLFFE 39

UBA-like domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 6320537      5 KVDEFMAITGADDAAiATQFIEMADGNLNTAISLFFENGGA 45
Cdd:pfam14555   3 LIAQFQAITGADEEV-ARQYLEAHNWDLEAAVNAFFDDGEA 42

Thioredoxin-related protein SoxW [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320537  221 KLDLDAAKQKARAKQKWIMINI-QDSGIFqCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNAQ--------PYLQFYH 291
Cdd:COG2143  26 LLDLEEDLALAKAEGKPILLFFeSDWCPY-CKKLHKEVFSDPEVAAYLKENFVVVQLDAEGDKEVtdfdgetlTEKELAR 104

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 6320537  292 LNNKDDLPHIAILDPiTGERVKQWNRVVPiPEQFISEIN 330
Cdd:COG2143 105 KYGVRGTPTLVFFDA-EGKEIARIPGYLK-PETFLALLK 141

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 6320537  219 MSKLDLDAAKQKARAKQKWIMINIQDSGIFQCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNAQPYLQFYHlnnKDDL 298
Cdd:cd02958   1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYK---VDKY 77

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6320537  299 PHIAILDPITGERVKQWNRVVPiPEQFISEINEFLASF 336
Cdd:cd02958  78 PHIAIIDPRTGEVLKVWSGNIT-PEDLLSQLIEFLEEF 114

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 6320537    223 DLDAAKQKARAKQKWIMINIQDSGIFQCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNAQPYLQFYHlnnkDDLPHIA 302
Cdd:pfam13899   5 DLEEALAAAAERGKPVLVDFGADWCFTCQVLERDFLSHEEVKAALAKNFVLLRLDWTSRDANITRAFDG----QGVPHIA 80

                  ....
gi 6320537    303 ILDP 306
Cdd:pfam13899  81 FLDP 84

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 6320537    3 EGKVDEFMAITGADDAAIATQFIEMADGNLNTAISLFFE 41
Cdd:cd14346   1 DEQISTFLAITGSEDAAVARQFLEMAGGDLETAVSLFFE 39

UBA-like domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 6320537      5 KVDEFMAITGADDAAiATQFIEMADGNLNTAISLFFENGGA 45
Cdd:pfam14555   3 LIAQFQAITGADEEV-ARQYLEAHNWDLEAAVNAFFDDGEA 42

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        40
                ....*....|....*....|....*....|....*....|.
gi 6320537    3 EGKVDEFMAITGADDAAiATQFIEMADGNLNTAISLFFENG 43
Cdd:cd14348   1 DELIAQFVSVTGADEDR-AKFFLESAGWDLEAALSSFFESG 40

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 6320537    9 FMAITGADdAAIATQFIEMADGNLNTAISLFF 40
Cdd:cd14273   1 FMEITGAD-PETARQYLESNNWDLEAAINLYF 31

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 6320537    6 VDEFMAITGADDAaIATQFIEMADGNLNTAISLFFE 41
Cdd:cd14345   3 IEQFTSITGADDT-VARHMLEACNGNLEMAVNMHLD 37

Ubiquitin regulatory domain X (UBX) found in NSFL1 cofactor (also known as UBX domain-containing protein 2C (UBXN2C) and similar proteins; UBXN2C, also termed NSFL1C, or NSFL1 cofactor p47, or p97 cofactor p47, UBX1, or UBXD10, 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. UBXN2C is a major adaptor 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 main role of the UBXN2C/p97 complex is in regulation of membrane fusion events. It plays an essential role in the reassembly of Golgi stacks at the end of mitosis. UBXN2C also functions as an essential factor for Golgi membrane fusion, which associates with the nuclear factor-kappaB essential modulator (NEMO) subunit of the IkappaB kinase (IKK) complex upon tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 stimulation, induces the lysosome-dependent degradation of polyubiquitinated NEMO without p97, and thus inhibits IKK activation. Moreover, UBXN2C regulates a membrane fusion process, which is required by the maintenance of the endoplasmic reticulum (ER) network, through phosphorylation by Cdc2 kinase.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6320537  419 TTRIQIRTGDGSRLVRRFNAlEDTVRTIYEVIKTEMDGFADSRFTL-NDHQREDLIDKlNMTIADAGLKNS 488
Cdd:cd17162   7 VTNIQIRLADGGRLVQKFNH-SHRIRDIRLFIVDARPAMAATSFVLmTTFPNKELTDE-NQTLKEANLLNA 75

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2B (UBXN2B) and similar proteins; UBXN2B, also termed NSFL1 cofactor p37, or p97 cofactor p37, 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. UBXN2B is an adaptor protein 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. UBXN2B forms a tight complex with p97 in the cytosol and localizes to the Golgi and endoplasmic reticulum (ER).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6320537  419 TTRIQIRTGDGSRLVRRFNaLEDTVRTIYEVIKTEMDGFADSRFTL-NDHQREDLIDKlNMTIADAGLKNSSLL 491
Cdd:cd17161   7 TTKIQIRLADGSRLIQRFN-QSHRIHDIRQFIVQSRPVFAASDFLLvTTFPNKELTDE-SQTLQEADILNTVIL 78

Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320537  223 DLDAAKQKARAKQKWIMINiqdsgiF------QCQALNRDLWSSRPVKTIIKENFVFLQYQYESRNA--QPYLQFYHLNN 294
Cdd:COG4232 308 DLEAALAEARAEGKPVFVD------FtadwcvTCKENERTVFSDPEVQAALADDVVLLKADVTDNDPeiTALLKRFGRFG 381

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6320537  295 kddLPHIAILDPiTGERVKQWNRVVPiPEQFISEINEFLA 334
Cdd:COG4232 382 ---VPTYVFYDP-DGEELPRLGFMLT-ADEFLAALEKAKG 416