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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034574091 208 KREYDQCRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHRGEelggGQDPVQLLSGFPRRAFSEADMERPLQELGLVPSA 287
Cdd:cd01772     1 KKEYDECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTD----GDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSA 76

                  ....*
gi 1034574091 288 VLIVA 292
Cdd:cd01772    77 VLIVT 81

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034574091 208 KREYDQCRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHRGEelggGQDPVQLLSGFPRRAFSEADMERPLQELGLVPSA 287
Cdd:cd01772     1 KKEYDECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTD----GDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSA 76

                  ....*
gi 1034574091 288 VLIVA 292
Cdd:cd01772    77 VLIVT 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 1034574091 210 EYDQCRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHRGEELgggqDPVQLLSGFPRRAFSEADMERPLQELGLVPSAVL 289
Cdd:pfam00789   1 AEDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDL----EPFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTL 76

                  ....
gi 1034574091 290 IVAK 293
Cdd:pfam00789  77 VLEP 80

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1034574091   6 ALESLIEMGFPRGRAEKALALTGNqGIEAAMDWL 39
Cdd:pfam00627   5 AIQRLVEMGFDREQVREALRATGN-NVERAAEYL 37

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034574091 208 KREYDQCRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHRGEelggGQDPVQLLSGFPRRAFSEADMERPLQELGLVPSA 287
Cdd:cd01772     1 KKEYDECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTD----GDGPFSLMTTFPRKVFTEEDMEKPLKELGLVPSA 76

                  ....*
gi 1034574091 288 VLIVA 292
Cdd:cd01772    77 VLIVT 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 1034574091 210 EYDQCRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHRGEELgggqDPVQLLSGFPRRAFSEADMERPLQELGLVPSAVL 289
Cdd:pfam00789   1 AEDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDL----EPFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTL 76

                  ....
gi 1034574091 290 IVAK 293
Cdd:pfam00789  77 VLEP 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034574091 214 CRIQVRLPDGTSLTQTFRAREQLAAVRLYVElhrgEELGGGQDPVQLLSGFPRRAFSEADMERPLQELGLVPSAVLIV 291
Cdd:cd16117     2 ARIQFRLPDGSSFTNQFPSDAPLEEARQFVA----QTVGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVV 75

UBA1 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034574091   6 ALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDDPDVD 49
Cdd:cd14385     4 ALAQLLGMGFPEVRCKKALLATGNSDAEAAMNWLFEHMDDPDID 47

UBA1 domain found in Arabidopsis thaliana ubiquitin carboxyl-terminal hydrolase 14 (atUBP14) and similar proteins; atUBP14, also called deubiquitinating enzyme 14, TITAN-6 protein, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is related to the isopeptidase T class of deubiquitinating enzymes that recycle polyubiquitin chains following protein degradation. atUBP14 is essential for early plant development. It can disassemble multi-ubiquitin chains linked internally via epsilon-amino isopeptide bonds using Lys48 and can process some, but not all, translational fusions of ubiquitin linked via alpha-amino peptide bonds. atUBP14 contains two ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034574091   7 LESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDDPD 47
Cdd:cd14295     5 VAQLMEMGFPKVRAEKALFFTQNKGLEEAMEWLEEHSEDAD 45

UBA domain found in plant PNGase/UBA or UBX (PUB) domain-containing proteins; This family includes some uncharacterized hypothetical proteins found in plants. Although their biological function remain unclear, all family members contain an N-terminal ubiquitin-associated (UBA) domain and a C-terminal PUB domain. UBA domain, along with UBL (ubiquitin-like) domain, has been implicated in proteasomal degradation by associating with substrates destined for degradation as well as with subunits of the proteasome, thus regulating protein turnover. PUB domain functions as a p97 (also known as valosin-containing protein or VCP) adaptor by interacting with the D1 and/or D2 ATPase domains. The type II AAA+ ATPase p97 is involved in a variety of cellular processes such as the deglycosylation of ERAD substrates, membrane fusion, transcription factor activation and cell cycle regulation through differential binding to specific adaptor proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034574091   6 ALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDDPDVD 49
Cdd:cd14290     6 LLKELEAMGFPRARAVRALHHTGNTSVEAAVNWIVEHENDPDID 49

UBA1 domain found in ubiquitin carboxyl-terminal hydrolase 5 (UBP5); UBP5, also called deubiquitinating enzyme 5, Isopeptidase T (IsoT), ubiquitin thioesterase 5, or ubiquitin-specific-processing protease 5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell. Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. ZnF domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin. This model corresponds to the UBA1 domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034574091   5 TALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDDPD 47
Cdd:cd14383     5 SVIIQLVEMGFPMDACRKAVYYTGNSGAEAAMNWVMSHMDDPD 47

UBA2 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA2 domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034574091   5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLMEH 42
Cdd:cd14297     2 DLVKQLVDMGFTEAQARKALRKTNNN-VERAVDWLFEG 38

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 11 (UBXN11) and similar proteins; UBXN11, also termed colorectal tumor-associated antigen COA-1, or socius, or UBX domain-containing protein 5 (UBXD5), 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. UBXN11 may function 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. UBXN11 also acts as a novel interacting partner of Rnd proteins (Rnd1, Rnd2, and Rnd3/RhoE), new members of Rho family of small GTPases. It directly binds to Rnd GTPases through its C-terminal region, and further participates in disassembly of actin stress fibers. UBXN11 also binds directly to Galpha12 and Galpha13 through its N-terminal region. As a novel activator of the Galpha12 family, UBXN11 promotes the Galpha12-induced RhoA activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034574091 212 DQCRIQVRLPDGTsltQTF----RAREQLAAVRLYVELHRGeelgGGQDPVQLLSGFPRRAFSeaDMERPLQELGLVPSA 287
Cdd:cd17077     1 DVTTLRIKSENGE---QTYilkmRFSDTIGDLRRYLDKHRS----KDAASYEIVTTFPNKVYD--DDSATLEELGLVPNA 71

                  ....
gi 1034574091 288 VLIV 291
Cdd:cd17077    72 TLHL 75

UBA domain found in ubiquitin-associated and SH3 domain-containing protein A (UBS3A) and similar proteins; UBS3A, also called Cbl-interacting protein 4 (CLIP4), suppressor of T-cell receptor signaling 2 (Sts-2), or T-cell ubiquitin ligand 1 (TULA-1), is a lymphoid protein only detected in thymus, spleen, and bone marrow. UBS3A exhibits extremely low phosphatase activity, but is capable of promoting T-cell apoptosis independent of either T cell receptor (TCR)/CD3-mediated signaling or caspase activity. It functions as a negative regulator of TCR signaling. UBS3A can also inhibit HIV-1 biogenesis through the binding of ATP-binding cassette protein family E member 1 (ABCE-1), a host factor of HIV-1 assembly. Moreover, UBS3A acts as the Cbl- and ubiquitin-interacting protein that can inhibit endocytosis and downregulation of ligand-activated epidermal growth factor receptor (EGFR) by impairing Cbl-induced ubiquitination, as well as inhibit clathrin-dependent endocytosis in general. This family also includes Arabidopsis thaliana ubiquitin carboxyl-terminal hydrolase 14 (atUBP14) and some uncharacterized AAA-type ATPase-like proteins found in plants.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1034574091   7 LESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEH 42
Cdd:cd14300     1 LETLLAMGFPEDVARKALKATGGKSIEKATDWLLSH 36

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 1034574091 215 RIQVRLPDGTSLTQTFRAREQLAAVRLYVELHRgeelGGGQDPVQLLSGFPRRAFSeaDMERPLQELGLVPSAVL 289
Cdd:cd01770     1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSAR----PGYSRPFVLMTGFPPKELT--DESQTLEEAGLLNAVVV 69

UBA domain found in yeast UBA domain-containing protein RUP1p and similar proteins; RUP1p is a ubiquitin-associated (UBA) domain-containing protein encoded by a nonessential yeast gene RUP1. It can mediate the association of Rsp5 and Ubp2. The N-terminal UBA domain is responsible for antagonizing Rsp5 function, as well as bridging the Rsp5-Ubp2 interaction. No other characterized functional domains or motifs are found in RUP1p.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034574091   5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLMEH 42
Cdd:cd14307     2 EAVASLLEMGIPREVAIEALRETNGD-VEAAANYIFSN 38

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034574091 214 CRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHrgEElggGQDPVQLLSGFPRRA-FSEADMERP----LQELGLVPSAV 288
Cdd:cd16120     1 VKILFKLPNGTRLERRFLKSDSLKVLYDFVFSH--ED---SPDKFQLVTNFPRRVlPCQPTEEQPnpptLEEAGLGKSEV 75

                  ...
gi 1034574091 289 LIV 291
Cdd:cd16120    76 LFV 78

UBA domain found in plant AAA-type ATPase-like proteins; This family includes some uncharacterized AAA-type ATPase-like proteins found in plant. The AAA+ ATPases function as molecular chaperons, ATPase subunits of proteases, helicases, or nucleic-acid stimulated ATPases. Members in this family contains an N-terminal ubiquitin-association (UBA) domain, a AAA-type ATPase domain and a C-terminal MgsA AAA+ ATPase domain. This model corresponds to the UBA domain which show a high level of sequence similarity with mammalian ubiquitin-associated and SH3 domain-containing protein A (UBS3A).

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1034574091   7 LESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEH 42
Cdd:cd14389     1 MEQLVDMGFSSDLAAEALAATGGKSTQKATEWILSH 36

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 7 (UBXN7) and similar proteins; UBXN7, also termed UBX domain-containing protein 7 (UBXD7), 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. 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 HIF1-alpha. It binds only to the active, NEDD8- or Rub1-modified form of cullins. In addition to having a UBX domain, UBXD7 contains a ubiquitin-associated (UBA), ubiquitin-associating (UAS), and ubiquitin-interacting motif (UIM) domains. Either UBA or UIM could serve as a docking site for neddylated-cullins. UBA domain is required for binding ubiquitylated-protein substrates, while the UIM motif is responsible for the binding to cullin RING ligases (CRLs), and the UBX domain is essential for p97 binding.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034574091 213 QCRIQVRLPDGTSLTQTFRAREQLAAVRLYVElhrgeELGGGQDPVQLLSGFPRRAFSEADMERPLQELGLVPSAVLIV 291
Cdd:cd01773     1 KSKLMLRFPDGKREQLSLPASAKLKALVKYVS-----SKGYPNERYELVTNFPRRKLSHLDYDITLKEAGLCPQETIFV 74

UBA domain found in uncharacterized protein At3g58460 from Arabidopsis thaliana and its homologs from other plants; The uncharacterized protein At3g58460 from Arabidopsis thaliana is also known as rhomboid-like protein 15 which is encoded by RBL15 gene. Although the biological function of the family members remains unclear, they all contain an N-terminal rhomboid-like domain and a C-terminal ubiquitin-associated (UBA) domain.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1034574091   6 ALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLM 40
Cdd:cd14287     3 LVQSLVAMGFEKHRARRALDAAGGD-INTAVEILM 36

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 1034574091 214 CRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHrgeeLGGGQDPVQLLSGFPRRAFSEADMErpLQELGLVPSAVL 289
Cdd:cd16118     1 AVIRVQFPDRLVLQAFFRPLETVRALYDFVKSH----LADPDLPFYLYTTPPKRVLKDKNKT--LYQAGLVPAALV 70

UBA domain found in probable E3 ubiquitin-protein ligase HERC2 and similar proteins; HERC2, also called HECT domain and RCC1-like domain-containing protein 2, is a SUMO-regulated E3 ubiquitin ligase that plays an important role in the SUMO-dependent pathway which orchestrates the DNA double-strand break (DSB) response. Moreover, HERC2 functions as a RNF8 auxiliary factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. In addition to a ubiquitin-association (UBA) domain, HERC2 contains more than one RCC1-like domains (RLDs) and a C-terminal HECT E3 ubiquitin ligase domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034574091  10 LIEMGFPRGRAEKAL-ALTGNQGI----EAAMDWLMEHED 44
Cdd:cd14402     6 LMEMGFPRKNVEFALkSLSGSSGGlptpEALVAWLLEHPD 45

UBA2 domain found in Kip1 ubiquitination-promoting complex protein 2 (KPC2) and similar proteins; KPC2, also called ubiquitin-associated domain-containing protein 1 (UBAC1), or glialblastoma cell differentiation-related protein 1, is one of two subunits of Kip1 ubiquitination-promoting complex (KPC), a novel E3 ubiquitin-protein ligase that also contains KPC1 subunit and regulates the ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p27 at G1 phase. KPC2 contains a ubiquitin-like (UBL) domain and two ubiquitin-associated (UBA) domains. This model corresponds to the UBA2 domain.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1034574091   5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLM 40
Cdd:cd14304     4 RAVQSLMEMGFEEEDVLEALRVTRNN-QNAACEWLL 38

UBA2 domain found in Saccharomyces cerevisiae ubiquitin carboxyl-terminal hydrolase 14 (scUBP14) and similar proteins; scUBP14, also called deubiquitinating enzyme 14, glucose-induced degradation protein 6, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is the yeast ortholog of human Isopeptidase T (USP5), a deubiquitinating enzyme known to bind the 29-linked polyubiquitin chains. scUBP14 has been identified as a K29-linked polyubiquitin binding protein as well. It is involved in K29-linked polyubiquitin metabolism by binding to the 29-linked Ub4 resin and serving as an internal positive control in budding yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA2 domain.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1034574091   6 ALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLMEH 42
Cdd:cd14298     3 ALAQLVSMGFDPEVARKALILTNGN-VERAIEWLFSN 38