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 767926356   1 MHKGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFPYV 80
Cdd:cd02958    1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767926356  81 SILDPRTGQKLVEWHQLD-VSSFLDQVTGFLGEH 113
Cdd:cd02958   81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

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 767926356   1 MHKGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFPYV 80
Cdd:cd02958    1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767926356  81 SILDPRTGQKLVEWHQLD-VSSFLDQVTGFLGEH 113
Cdd:cd02958   81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

UAS domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926356     1 MHKGSFETAKECGQMQ--NKWLMINIQNVQDfaCQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFP 78
Cdd:smart00594  11 FYQGSLEAAKQEASRQrrLLWLYLHSQDSPD--SQVFNRDVLCNEAVKSLIRENFIFWQVDVDTSEGQRVSQFYKLDSFP 88

                           90       100       110
                   ....*....|....*....|....*....|....
gi 767926356    79 YVSILDPRTGQKLVEWHQLDVSSFLDQVTGFLGE 112
Cdd:smart00594  89 YVAIVDPRTGQRVIEWVGVVEGEISPEELMTFLE 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 767926356    3 KGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGdFPYVSI 82
Cdd:pfam13899   3 LSDLEEALAAAAERGKPVLVDFGADWCFTCQVLERDFLSHEEVKAALAKNFVLLRLDWTSRDANITRAFDGQG-VPHIAF 81

                  ...
gi 767926356   83 LDP 85
Cdd:pfam13899  82 LDP 84

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 767926356   1 MHKGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFPYV 80
Cdd:cd02958    1 FFQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSSEGQRFLQSYKVDKYPHI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767926356  81 SILDPRTGQKLVEWHQLD-VSSFLDQVTGFLGEH 113
Cdd:cd02958   81 AIIDPRTGEVLKVWSGNItPEDLLSQLIEFLEEF 114

UAS domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926356     1 MHKGSFETAKECGQMQ--NKWLMINIQNVQDfaCQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGDFP 78
Cdd:smart00594  11 FYQGSLEAAKQEASRQrrLLWLYLHSQDSPD--SQVFNRDVLCNEAVKSLIRENFIFWQVDVDTSEGQRVSQFYKLDSFP 88

                           90       100       110
                   ....*....|....*....|....*....|....
gi 767926356    79 YVSILDPRTGQKLVEWHQLDVSSFLDQVTGFLGE 112
Cdd:smart00594  89 YVAIVDPRTGQRVIEWVGVVEGEISPEELMTFLE 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 767926356 263 PKAQLMLRYPDGKREQITLPEQAKLLALVKHVQSKGYPNERFELLTNFPRRKLSHLDYDITLQEAGLCPQETVFVQER 340
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 767926356    3 KGSFETAKECGQMQNKWLMINIQNVQDFACQCLNRDVWSNEAVKNIIREHFIFWQVYHDSEEGQRYIQFYKLGdFPYVSI 82
Cdd:pfam13899   3 LSDLEEALAAAAERGKPVLVDFGADWCFTCQVLERDFLSHEEVKAALAKNFVLLRLDWTSRDANITRAFDGQG-VPHIAF 81

                  ...
gi 767926356   83 LDP 85
Cdd:pfam13899  82 LDP 84

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 767926356 266 QLMLRYPDGKR-EQITLPEQaKLLALVKHVQSKGYPNERFELLTNFPRRKL-----SHLDYDITLQEAGLCPQETVFVQ 338
Cdd:cd16120    2 KILFKLPNGTRlERRFLKSD-SLKVLYDFVFSHEDSPDKFQLVTNFPRRVLpcqptEEQPNPPTLEEAGLGKSEVLFVQ 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767926356 265 AQLMLRYPDGKREQITLPEQAKLLALVKHVQ-SKGYPNERFELLTNFPRRKLSHLDYDITLQEAGLCP 331
Cdd:cd01772    7 CRLQVRLTNGSTLTQTFGAKEQLAAVRLYVElNRTDGDGPFSLMTTFPRKVFTEEDMEKPLKELGLVP 74

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 8 (UBXN8) and similar proteins; UBXN8, also termed reproduction 8 protein (Rep8), or UBX domain-containing protein 6 (UBXD6), or D8S2298E, 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. UBXN8 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. UBXN8 is a transmembrane protein that localizes to the endoplasmic reticulum (ER) membrane with its UBX domain facing the cytoplasm. It facilitates efficient ER-associated degradation (ERAD) by tethering p97 to the ER membrane.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767926356 269 LRYPDGKREQITLPEQAKLLALVKHVQSKGYPNERFELLTNFPRRKLSHlDYDITLQEAGLCPQETVFVQE 339
Cdd:cd01774    7 LRFPGGRVHRRRFLTTENIQVLLDWMTKLGYHQTLYTLSTTYPRTILSD-DADKTLEDLGITKDVALNVEE 76

Ubiquitin regulatory domain X (UBX) 2 found in UBX domain protein 9 (UBXN9, UBXD9, or ASPSCR1) and similar proteins; UBXN9, also termed tether containing UBX domain for GLUT4 (TUG), or alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1), or alveolar soft part sarcoma locus (ASPL), or renal papillary cell carcinoma protein 17 (RCC17), belongs to the UBXD family of proteins that contains two ubiquitin regulatory domains 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, UBXN9 contains an N-terminal ubiquitin-like (Ubl) domain. UBXN9 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. However, high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers; the extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers.UBXN9 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4, assembly of the Golgi apparatus. In addition to GLUT4, UBXN9 also controls vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. UBXN9 and its budding yeast ortholog, Ubx4p, are multifunctional proteins that share some, but not all functions. Yeast Ubx4p is important for endoplasmic reticulum-associated protein degradation (ERAD) but UBXN9 appears not to share this function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767926356 265 AQLMLRYPDGKREQITLPEQAKLLALVKHVQSK-GYPNERFELLTNFPRRKLShlDYDITLQEAGLCPQETVFV 337
Cdd:cd16118    1 AVIRVQFPDRLVLQAFFRPLETVRALYDFVKSHlADPDLPFYLYTTPPKRVLK--DKNKTLYQAGLVPAALVYF 72