Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar proteins; UBXN2A, also termed UBX domain-containing protein 4 (UBXD4), 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. UBXN2A functions as a p97 (also known as VCP or Cdc48) adaptor protein facilitating the regulation of the cell surface number and stability of alpha3-containing neuronal nicotinic acetylcholine receptors (nAChRs). It also regulates nicotinic receptor degradation by modulating the E3 ligase activity of carboxyl terminus of Hsc70 interacting protein (CHIP) that is involved in the degradation of several disease-related proteins. In addition, UBXN2A is an important anticancer factor that contributes to p53 localization and activation as a host defense mechanism against cancerous growth. It acts as a potential mortalin inhibitor, as well as a potential chemotherapy sensitizer for clinical application. It binds to the oncoprotein mortalin-2 (mot-2), and further unsequesters p53 from mot-2 in the cytoplasm, resulting in translocation of p53 to the nucleus where p53 proteins activate their downstream biological effects, including apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530367285 167 LNNLEPITNIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQRSPPFSLATALPVLRLLDETLTLEEADLQNAVIIQR 246
Cdd:cd17160    1 LNELEPITNIQIWLADGRRIVQKFNLSHRISHVRDFVEKIQGSSMSVPFTLATSLPFRELLDETLTLQEADLQNAVIVQR 80

                 ....
gi 530367285 247 LQKT 250
Cdd:cd17160   81 LQKT 84

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar proteins; UBXN2A, also termed UBX domain-containing protein 4 (UBXD4), 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. UBXN2A functions as a p97 (also known as VCP or Cdc48) adaptor protein facilitating the regulation of the cell surface number and stability of alpha3-containing neuronal nicotinic acetylcholine receptors (nAChRs). It also regulates nicotinic receptor degradation by modulating the E3 ligase activity of carboxyl terminus of Hsc70 interacting protein (CHIP) that is involved in the degradation of several disease-related proteins. In addition, UBXN2A is an important anticancer factor that contributes to p53 localization and activation as a host defense mechanism against cancerous growth. It acts as a potential mortalin inhibitor, as well as a potential chemotherapy sensitizer for clinical application. It binds to the oncoprotein mortalin-2 (mot-2), and further unsequesters p53 from mot-2 in the cytoplasm, resulting in translocation of p53 to the nucleus where p53 proteins activate their downstream biological effects, including apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530367285 167 LNNLEPITNIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQRSPPFSLATALPVLRLLDETLTLEEADLQNAVIIQR 246
Cdd:cd17160    1 LNELEPITNIQIWLADGRRIVQKFNLSHRISHVRDFVEKIQGSSMSVPFTLATSLPFRELLDETLTLQEADLQNAVIVQR 80

                 ....
gi 530367285 247 LQKT 250
Cdd:cd17160   81 LQKT 84

Domain present in Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530367285    59 KQVDVNIKLWKNGFTVND-DFRSYSDGASQQFLNSIKKGELPSELQGIFDKEEVDVKVEDKKNEICLSTKPVFQPFSGQG 137
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDgPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|..
gi 530367285   138 HRLGSATPKIVS 149
Cdd:smart00553  81 QKLGSPGPQSLS 92

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530367285   174 TNIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQrSPPFSLATALP---VLRLLDETLTLEEADLQNAVIIQR 246
Cdd:smart00166   2 CRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAALGDG-NDPFTLNSPFPrrtFTKDDYSKKLLELALLPSSTLVLE 76

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar proteins; UBXN2A, also termed UBX domain-containing protein 4 (UBXD4), 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. UBXN2A functions as a p97 (also known as VCP or Cdc48) adaptor protein facilitating the regulation of the cell surface number and stability of alpha3-containing neuronal nicotinic acetylcholine receptors (nAChRs). It also regulates nicotinic receptor degradation by modulating the E3 ligase activity of carboxyl terminus of Hsc70 interacting protein (CHIP) that is involved in the degradation of several disease-related proteins. In addition, UBXN2A is an important anticancer factor that contributes to p53 localization and activation as a host defense mechanism against cancerous growth. It acts as a potential mortalin inhibitor, as well as a potential chemotherapy sensitizer for clinical application. It binds to the oncoprotein mortalin-2 (mot-2), and further unsequesters p53 from mot-2 in the cytoplasm, resulting in translocation of p53 to the nucleus where p53 proteins activate their downstream biological effects, including apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530367285 167 LNNLEPITNIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQRSPPFSLATALPVLRLLDETLTLEEADLQNAVIIQR 246
Cdd:cd17160    1 LNELEPITNIQIWLADGRRIVQKFNLSHRISHVRDFVEKIQGSSMSVPFTLATSLPFRELLDETLTLQEADLQNAVIVQR 80

                 ....
gi 530367285 247 LQKT 250
Cdd:cd17160   81 LQKT 84

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 530367285 175 NIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQrSPPFSLATALPVLRLLDETLTLEEADLQNAVIIQR 246
Cdd:cd01770    1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSARPGY-SRPFVLMTGFPPKELTDESQTLEEAGLLNAVVVQK 71

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530367285 167 LNNLEPITNIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQRSPPFSLATALPVLRLLDETLTLEEADLQNAVIIQR 246
Cdd:cd17162    1 INDSEPVTNIQIRLADGGRLVQKFNHSHRIRDIRLFIVDARPAMAATSFVLMTTFPNKELTDENQTLKEANLLNAVIVQR 80

                 .
gi 530367285 247 L 247
Cdd:cd17162   81 L 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530367285  171 EPITNIQIWLANGKRIVQKFNITHRVSHIKDFIEkYQGSQRSPPFSLATALP--VLRLLDETLTLEEADL-QNAVIIQRL 247
Cdd:pfam00789   2 EDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVD-SNRYDDLEPFSLNTPFPrrPLTDLDYSKTLKEAGLlPNSTLVLEP 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530367285 174 TNIQIWLANGKRIVQKFNITHRVSHIKDFIEKYQGSQrSPPFSLATALP--VLRLLDETLTLEEADL-QNAVII 244
Cdd:cd01772    7 CRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTDG-DGPFSLMTTFPrkVFTEEDMEKPLKELGLvPSAVLI 79

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 530367285 171 EPITNIQIWLANGKRIVQKFNITHRVSHIKDFIekyqGSQRSPP--FSLATALP--VLRLLDETLTLEEADL 238
Cdd:cd01771    2 EPISKLRFRLPGGEFLTRRFLASEPLQVLLNFV----ASKGYPPdeYKLLTTFPrrDLTQLDPSKTLEELKL 69