UBA domain found in UBX domain-containing protein 1 (UBXN1) and similar proteins; UBXN1, also called SAPK substrate protein 1 (SAKS1) or UBA/UBX 33.3 kDa protein, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (UBX) domain. It binds polyubiquitin and valosin-containing protein (VCP), and has been identified as a substrate for stress-activated protein kinases (SAPKs). Moreover, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and may be involved in the Ub-proteasome proteolytic pathways. In addition, UBXN1 can associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21361517   5 TALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDD 45
Cdd:cd14302   1 SELQTLIEMGFSRNRAEKALAKTGNQGVEAAMEWLLAHEDD 41

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361517    213 QCRIQVRLPDGTSLTQTFRAREQLAAVRLYVelhrGEELGGGQDPVQLLSGFPRRAFSEADMERPLQELG 282
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFV----SAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELA 66

UBA domain found in UBX domain-containing protein 1 (UBXN1) and similar proteins; UBXN1, also called SAPK substrate protein 1 (SAKS1) or UBA/UBX 33.3 kDa protein, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (UBX) domain. It binds polyubiquitin and valosin-containing protein (VCP), and has been identified as a substrate for stress-activated protein kinases (SAPKs). Moreover, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and may be involved in the Ub-proteasome proteolytic pathways. In addition, UBXN1 can associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21361517   5 TALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDD 45
Cdd:cd14302   1 SELQTLIEMGFSRNRAEKALAKTGNQGVEAAMEWLLAHEDD 41

Ubiquitin associated domain; Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 21361517      5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLM 40
Cdd:smart00165   3 EKIDQLLEMGFSREEALKALRAANGN-VERAAEYLL 37

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21361517    213 QCRIQVRLPDGTSLTQTFRAREQLAAVRLYVelhrGEELGGGQDPVQLLSGFPRRAFSEADMERPLQELG 282
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFV----SAALGDGNDPFTLNSPFPRRTFTKDDYSKKLLELA 66

UBA domain found in UBX domain-containing protein 1 (UBXN1) and similar proteins; UBXN1, also called SAPK substrate protein 1 (SAKS1) or UBA/UBX 33.3 kDa protein, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (UBX) domain. It binds polyubiquitin and valosin-containing protein (VCP), and has been identified as a substrate for stress-activated protein kinases (SAPKs). Moreover, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and may be involved in the Ub-proteasome proteolytic pathways. In addition, UBXN1 can associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21361517   5 TALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDD 45
Cdd:cd14302   1 SELQTLIEMGFSRNRAEKALAKTGNQGVEAAMEWLLAHEDD 41

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 21361517 214 CRIQVRLPDGTSLTQTFRAREQLAAVRLYVElhrgEELGGGQDPVQLLSGFPRRAFSEADMERPLQELGMA 284
Cdd:cd16117   2 ARIQFRLPDGSSFTNQFPSDAPLEEARQFVA----QTVGPAYGPFSLATTFPRREFTDDDYQKTLLELELA 68

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 21361517   7 LESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDDPD 47
Cdd:cd14295   5 VAQLMEMGFPKVRAEKALFFTQNKGLEEAMEWLEEHSEDAD 45

UBA domain found in ubiquitin-associated and SH3 domain-containing protein B (UBS3B) and similar proteins; UBS3B, or Cbl-interacting protein p70, suppressor of T-cell receptor signaling 1 (Sts-1), T-cell ubiquitin ligand 2 (TULA-2), or tyrosine-protein phosphatase STS1/TULA2, is ubiquitously expressed in mammalian tissues in a variety of cell types. It exhibits high phosphatase activity, but demonstrates no proapoptotic activity. It negatively regulates the tyrosine kinase Zap-70 activation and T cell receptor (TCR) signaling pathways that modulate T cell activation. Moreover, UBS3B acts as a Cbl- and ubiquitin-interacting protein that inhibits endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 21361517   5 TALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEH 42
Cdd:cd14301   1 SALEVLLSMGFPKHRAEKALAATGGRSVQLASDWLLSH 38

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 21361517   6 ALESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEHEDDPDVD 49
Cdd:cd14290   6 LLKELEAMGFPRARAVRALHHTGNTSVEAAVNWIVEHENDPDID 49

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 21361517   5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLMEH 42
Cdd:cd14297   2 DLVKQLVDMGFTEAQARKALRKTNNN-VERAVDWLFEG 38

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 21361517   7 LESLIEMGFPRGRAEKALALTGNQGIEAAMDWLMEH 42
Cdd:cd14300   1 LETLLAMGFPEDVARKALKATGGKSIEKATDWLLSH 36

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 21361517 214 CRIQVRLPDGTSLTQTFRAREQLAAVRLYVELHrgeelGGGQDPVQLLSGFPRRAFSEADMERPLQELGMAARlET 289
Cdd:cd01771   5 SKLRFRLPGGEFLTRRFLASEPLQVLLNFVASK-----GYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQ-ET 74

UBA2 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 UBA2 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21361517   6 ALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLMEHEDD 45
Cdd:cd14386   5 AVAMLVSMGFTRDQAIKALKATDNN-VERAADWIFSHPDE 43

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 21361517     6 ALESLIEMGFPRGRAEKALALTGNqGIEAAMDWL 39
Cdd:pfam00627   5 AIQRLVEMGFDREQVREALRATGN-NVERAAEYL 37

Ubiquitin associated domain; Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 21361517      5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLM 40
Cdd:smart00165   3 EKIDQLLEMGFSREEALKALRAANGN-VERAAEYLL 37

UBA domain found in vacuolar protein sorting-associated protein 13D (VP13D) and similar proteins; VP13D is a chorea-acanthocytosis (CHAC)-similar protein encoded by gene VPS13D. it contains two putative domains, ubiquitin-associated (UBA) domain and lectin domain of ricin B chain profile (ricin-B-lectin), suggesting it may interact with, and be involved in the trafficking of, proteins modified with ubiquitin and/or carbohydrate molecules. Further investigation is required.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 21361517   7 LESLIEMGFPRGRAEKALALTGNQgIEAAMDWLMEH 42
Cdd:cd14306   1 VAKLMELGFPEEDCIRALRACGGN-VEEAANWLLEN 35

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 6 (UBXN6) and similar proteins; UBXN6, also termed UBX domain-containing protein 1 (UBXD1), and UBXDC2, 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. UBXN6 acts 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. Unlike other p97 cofactors that binds the N-domain of p97 through their UBX domain, UBXN6 binds p97 in two regions, at the p97 C terminus via a PUB domain and at the p97 N-domain with a short linear interaction motif termed VIM. Its UBX domain is not functional for the binding of p97. The UBXN6-p97 complex regulates the endolysosomal sorting of ubiquitylated plasma membrane protein caveolin-1 (CAV1), as well as the trafficking of ERGIC-53-containing vesicles by controlling the interaction of transport factors with the cytoplasmic tail of ERGIC-53. In addition, UBXN6 is a regulatory component of endoplasmic reticulum-associated degradation (ERAD) that may modulate the adaptor binding to p97.

                        10        20        30
                ....*....|....*....|....*....|
gi 21361517 214 CRIQVRLPDGTSLTQTFRAREQLAAVRLYV 243
Cdd:cd16119   2 TLIRVRFPDGVILQGTFYAREKLSAVREFV 31

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 21361517  10 LIEMGFPRGRAEKAL-ALTGNQGI----EAAMDWLMEHED 44
Cdd:cd14402   6 LMEMGFPRKNVEFALkSLSGSSGGlptpEALVAWLLEHPD 45

UBA domain found in probable E3 ubiquitin-protein ligase HERC1, HERC2 and similar proteins; HERC1, also called HECT domain and RCC1-like domain-containing protein 1, p532, or p619, is an ubiquitously expressed giant protein involved in ubiquitin-dependent intracellular membrane trafficking through its interaction with vesicle coat proteins such as clathrin and ARF. Moreover, it has been identified as a tuberous sclerosis complex TSC2-interacting protein that may play a role in TSC-mTOR (mammalian target of rapamycin) pathway. 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. HERC1 and HERC2 are multi-domain proteins with different domain organizations. Both of them contain a ubiquitin-association (UBA) domain, more than one RCC1-like domains (RLDs) and a C-terminal HECT E3 ubiquitin ligase domain.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 21361517  10 LIEMGFPRGRAEKALALTGN----QGIEAAMDWLMEH 42
Cdd:cd14331   4 LMEMGFSRRQIEMAMQALGSesdaPNIENLVNWLLEH 40

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 21361517   5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLM 40
Cdd:cd14304   4 RAVQSLMEMGFEEEDVLEALRVTRNN-QNAACEWLL 38

UBA domain found in Arabidopsis thaliana DNA (cytosine-5)-methyltransferase DRM2 (atDRM2) and similar proteins; atDRM2, also called protein domains rearranged methylase 2, is a homolog of the mammalian de novo methyltransferase DNMT3. It is the major de novo methyltransferase targeted to DNA by small interfering RNAs (siRNAs) in the RNA-directed DNA methylation (RdDM) pathway in Arabidopsis thaliana. atDRM2 is a part of the RdDM effector complex and plays a catalytic role in RdDM. It contains an N-terminal UBA domains and a C-terminal methyltransferase domain, both of which are required for normal RdDM.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 21361517   5 TALESLIEMGFPRGRAEKALALTGNQgIEAAMDWLME 41
Cdd:cd14330   2 EKIKTLVSMGFSESDARRALERCGYD-VAAAADFLFS 37