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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 23272590 319 VARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQTVGNTYGNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVLLP 395
Cdd:cd16117   1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVVLP 77

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 23272590 319 VARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQTVGNTYGNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVLLP 395
Cdd:cd16117   1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVVLP 77

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23272590   317 STVARIQFRLPDGSSFTNQFPSDAPLEEARQF-AAQTVGNTYgNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVLLP 395
Cdd:pfam00789   2 EDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFvDSNRYDDLE-PFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTLVLEP 80

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 23272590 319 VARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQTVGNTYGNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVLLP 395
Cdd:cd16117   1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVVLP 77

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23272590   317 STVARIQFRLPDGSSFTNQFPSDAPLEEARQF-AAQTVGNTYgNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVLLP 395
Cdd:pfam00789   2 EDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFvDSNRYDDLE-PFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTLVLEP 80

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 23272590 318 TVARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQTVGNTYGNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVL 393
Cdd:cd01772   5 DECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTDGDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSAVLIV 80

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 23272590 319 VARIQFRLPDGSSFTNQFPSDAPLEEARQFAAqTVGNTYGNFSLATMFPRREFTKEDYKKKLLDLELAPSASVVL 393
Cdd:cd01771   4 ISKLRFRLPGGEFLTRRFLASEPLQVLLNFVA-SKGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQETLFL 77

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 23272590 325 RLPDGSSFTNQF-PSDApLEEARQFAAQTVGNTYGNFSLATM-FPRREFTkeDYKKKLLDLELaPSASVVLL 394
Cdd:cd17076   8 RLPDGQRFQRFFrPSDT-LQDVLAFAESQSGLDLSNCIIETNeVPRRVFS--DLSKTIAECGI-QDKTVLYI 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).

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 23272590 321 RIQFRLPDGSSFTNQFPSDAPLEEARQFAAQTVGN-TYGNFSLATMFPRREFTKED 375
Cdd:cd17161   9 KIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVfAASDFLLVTTFPNKELTDES 64