Ubiquitin regulatory domain X (UBX) found in UBX domain-containing proteins UBXN2A, UBXN2B, NSFL1C/UBXN2C, and similar proteins; This family includes UBX domain-containing proteins UBXN2A, UBXN2B, and NSFL1C/UBXN2C, which contain a SEP (Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47) domain, and a ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold at the C-terminus. UBX domain participates broadly in the regulation of protein degradation. UBXN2A, UBXN2B, and UBXN2C function as the adaptor proteins 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18412499 231 SIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLTDLTQTIEEAGLANSVVLQK 302
Cdd:cd01770   1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSARPGYSRPFVLMTG-FPPKELTDESQTLEEAGLLNAVVVQK 71

Ubiquitin regulatory domain X (UBX) found in UBX domain-containing proteins UBXN2A, UBXN2B, NSFL1C/UBXN2C, and similar proteins; This family includes UBX domain-containing proteins UBXN2A, UBXN2B, and NSFL1C/UBXN2C, which contain a SEP (Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47) domain, and a ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold at the C-terminus. UBX domain participates broadly in the regulation of protein degradation. UBXN2A, UBXN2B, and UBXN2C function as the adaptor proteins 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18412499 231 SIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLTDLTQTIEEAGLANSVVLQK 302
Cdd:cd01770   1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSARPGYSRPFVLMTG-FPPKELTDESQTLEEAGLLNAVVVQK 71

SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47. In p47, the SEP domain has been shown to bind to and inhibit the cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18412499   114 IVFWSNGFTIDDGPLRKLDDPENASFLESIRKSECPKELEPADRRAPVHVNLM-RKEEKCPERQKRRVSFQGVGR 187
Cdd:pfam08059   1 LTFWRNGFSVDDGPLRRYDDPANAEFLEAINRGEAPLELLNVAPGQGVDVNLEdRRDEDYVPPKKKYKPFSGSGR 75

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18412499    229 TTSIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLTDL---TQTIEEAGLANSVVLQK 302
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAALGDGNDPFTLNSP-FPRRTFTKDdysKKLLELALLPSSTLVLE 76

Ubiquitin regulatory domain X (UBX) found in UBX domain-containing proteins UBXN2A, UBXN2B, NSFL1C/UBXN2C, and similar proteins; This family includes UBX domain-containing proteins UBXN2A, UBXN2B, and NSFL1C/UBXN2C, which contain a SEP (Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47) domain, and a ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold at the C-terminus. UBX domain participates broadly in the regulation of protein degradation. UBXN2A, UBXN2B, and UBXN2C function as the adaptor proteins 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18412499 231 SIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLTDLTQTIEEAGLANSVVLQK 302
Cdd:cd01770   1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSARPGYSRPFVLMTG-FPPKELTDESQTLEEAGLLNAVVVQK 71

SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47. In p47, the SEP domain has been shown to bind to and inhibit the cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18412499   114 IVFWSNGFTIDDGPLRKLDDPENASFLESIRKSECPKELEPADRRAPVHVNLM-RKEEKCPERQKRRVSFQGVGR 187
Cdd:pfam08059   1 LTFWRNGFSVDDGPLRRYDDPANAEFLEAINRGEAPLELLNVAPGQGVDVNLEdRRDEDYVPPKKKYKPFSGSGR 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18412499 223 IDETVPTTSIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPG-ASLNYQLQTMgFPPKPLTDLTQTIEEAGLANSVVLQ 301
Cdd:cd17161   1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVfAASDFLLVTT-FPNKELTDESQTLQEADILNTVILQ 79

                ..
gi 18412499 302 KF 303
Cdd:cd17161  80 RL 81

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 18412499 231 SIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLTDL--TQTIEEAGLANSVVL 300
Cdd:cd01767   1 RIQIRLPDGSRIQRRFSKSDTLQDLYDFVESNLGDSPSSFSLVTS-FPRRVLTDEdsDKTLEELGLTPNAVL 71

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18412499    229 TTSIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLTDL---TQTIEEAGLANSVVLQK 302
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAALGDGNDPFTLNSP-FPRRTFTKDdysKKLLELALLPSSTLVLE 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18412499 229 TTSIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTmGFPPKPLT--DLTQTIEEAGLANSVVL 300
Cdd:cd01772   6 ECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTDGDGPFSLMT-TFPRKVFTeeDMEKPLKELGLVPSAVL 78

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 18412499 229 TTSIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgFPPKPLT--DLTQTIEEAGLANSVVL 300
Cdd:cd16117   1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPAYGPFSLATT-FPRREFTddDYQKTLLELELAPSAAL 73

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 18412499 230 TSIQLRLADGTRLVAKFNHHHTVNDIRGFIDSSRPGASLNYQLQTMgfPPK-PLTDLTQTIEEAGLA-NSVV 299
Cdd:cd16118   1 AVIRVQFPDRLVLQAFFRPLETVRALYDFVKSHLADPDLPFYLYTT--PPKrVLKDKNKTLYQAGLVpAALV 70