UBA domain-like superfamily; The ubiquitin-associated (UBA) domain-like superfamily contains alpha-helical structural homology ubiquitin-binding domains, including UBA domains and coupling of ubiquitin conjugation to endoplasmic reticulum degradation (CUE) domains which share a common three-helical bundle architecture. UBA domains are commonly occurring sequence motifs found in proteins involved in ubiquitin-mediated proteolysis. They contribute to ubiquitin (Ub) binding or ubiquitin-like (UbL) domain binding. However, some kinds of UBA domains can only bind the UbL domain, but not the Ub domain. UBA domains are normally comprised of compact three-helix bundles which contain a conserved GF/Y-loop. They can bind polyubiquitin with high affinity. They also bind monoubiquitin and other proteins. Most UBA domain-containing proteins have one UBA domain, but some harbor two or three UBA domains. CUE domain containing proteins are characterized by an FP and a di-leucine-like sequence and bind to monoubiquitin with varying affinities. Some higher eukaryotic CUE domain proteins do not bind monoubiquitin efficiently, since they carry LP, rather than FP among CUE domains. This superfamily also includes many UBA-like domains found in AMP-activated protein kinase (AMPK) related kinases, the NXF family of mRNA nuclear export factors, elongation factor Ts (EF-Ts), nascent polypeptide-associated complex subunit alpha (NACA) and similar proteins. Although many UBA-like domains may have a conserved TG but not GF/Y-loop, they still show a high level of structural and sequence similarity with three-helical ubiquitin binding domains.

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gi 914615973 60 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:cd14390   1 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 38

UBA domain of vertebrate ubiquitin-conjugating enzyme E2 K (UBE2K); UBE2K, also called Huntingtin-interacting protein 2 (HIP-2), ubiquitin carrier protein, ubiquitin-conjugating enzyme E2-25 kDa (E2-25K), or ubiquitin-protein ligase is a multi-ubiquitinating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains which is involved in the ubiquitin (Ub)-dependent proteolytic pathway. It interacts with the frameshift mutant of ubiquitin B and functions as a crucial factor regulating amyloid-beta neurotoxicity. It has also been characterized as Huntingtin-interacting protein that modulates the neurotoxicity of Amyloid-beta (Abeta), the principal protein involved in Alzheimer's disease pathogenesis. Moreover, E2-25K increases aggregate the formation of expanded polyglutamine proteins and polyglutamine-induced cell death in the pathology of polyglutamine diseases. UBE2K and its yeast homolog UBC1 are unique class II E2 conjugating enzymes, both of which contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

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gi 914615973 60 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:cd14390   1 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 38

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

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gi 914615973   59 YTKKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:smart00165  1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYLL 37

ubiquitin-conjugating enzyme; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 914615973   1 MTLRTVLLSLQALLAAAEPDDPQDAVVANQYKQNPEMFKQTARLWAHVYAG 51
Cdd:PTZ00390  98 LQIRTVLLSIQALLSAPEPDDPLDTSVADHFKNNRADAEKVAREWNQKYAK 148

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

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                  ....*....|....*....|....*....|....*....|..
gi 914615973   56 SPEYTKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:TIGR00601 334 TPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQ 375

UBA domain of vertebrate ubiquitin-conjugating enzyme E2 K (UBE2K); UBE2K, also called Huntingtin-interacting protein 2 (HIP-2), ubiquitin carrier protein, ubiquitin-conjugating enzyme E2-25 kDa (E2-25K), or ubiquitin-protein ligase is a multi-ubiquitinating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains which is involved in the ubiquitin (Ub)-dependent proteolytic pathway. It interacts with the frameshift mutant of ubiquitin B and functions as a crucial factor regulating amyloid-beta neurotoxicity. It has also been characterized as Huntingtin-interacting protein that modulates the neurotoxicity of Amyloid-beta (Abeta), the principal protein involved in Alzheimer's disease pathogenesis. Moreover, E2-25K increases aggregate the formation of expanded polyglutamine proteins and polyglutamine-induced cell death in the pathology of polyglutamine diseases. UBE2K and its yeast homolog UBC1 are unique class II E2 conjugating enzymes, both of which contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

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                ....*....|....*....|....*....|....*...
gi 914615973 60 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:cd14390   1 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 38

UBA domain found in vertebrate ubiquitin-conjugating enzyme E2 K (UBE2K), Drosophila melanogaster ubiquitin-conjugating enzyme E2-22 kDa (UbcD4) and similar proteins; UBE2K, also called Huntingtin-interacting protein 2 (HIP-2), ubiquitin carrier protein, ubiquitin-conjugating enzyme E2-25 kDa (E2-25K), or ubiquitin-protein ligase, is a multi-ubiquitinating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains which is involved in the ubiquitin (Ub)-dependent proteolytic pathway. It interacts with the frameshift mutant of ubiquitin B and functions as a crucial factor regulating amyloid-beta neurotoxicity. It has also been characterized as Huntingtin-interacting protein that modulates the neurotoxicity of Amyloid-beta (Abeta), the principal protein involved in Alzheimer's disease pathogenesis. Moreover, E2-25K increases aggregate the formation of expanded polyglutamine proteins and polyglutamine-induced cell death in the pathology of polyglutamine diseases. UbcD4, also called ubiquitin carrier protein, or ubiquitin-protein ligase, is encoded by Drosophila E2 gene which is only expressed in pole cells in embryos. It is a putative E2 enzyme homologous to the Huntingtin interacting protein-2 (HIP2) of human. UbcD4 specifically interacts with the polyubiquitin-binding subunit of the proteasome. This family also includes a putative ubiquitin conjugating enzyme from plasmodium Yoelii (pyUCE). It shows a high level of sequence similarity with UBE2K and may also plays a role in the ubiquitin-mediated protein degradation pathway. All family members are class II E2 conjugating enzymes which contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

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gi 914615973 60 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:cd14313   1 KKKVDKLVDMGFDRDEAIVALSSNNWNLERATEYLF 36

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.

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gi 914615973  58 EYTKKIENLCAMGFDRNAVIVALSSKSWDVETATELL 94
Cdd:pfam00627  1 EDEEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

UBA domain found in Drosophila melanogaster ubiquitin-conjugating enzyme E2-22 kDa (UbcD4) and similar proteins; UbcD4, also called ubiquitin carrier protein or ubiquitin-protein ligase, is a class II E2 ubiquitin-conjugating enzyme encoded by Drosophila E2 gene which is only expressed in pole cells in embryos. It is a putative E2 enzyme homologous to the Huntingtin interacting protein-2 (HIP2) of human. UbcD4 specifically interacts with the polyubiquitin-binding subunit of the proteasome. It contains a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

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gi 914615973 62 KIENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:cd14391   3 KIRQLMDMGFDEHKARVALSSHNWDLEKATESLF 36

Ubiquitin-conjugating enzyme; Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologs. TSG101 is one of several UBC homologs that lacks this active site cysteine.

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gi 914615973    1 MTLRTVLLSLQALLAAAEPDDPQDAVVANQYKQNPEMFKQTARLWA 46
Cdd:pfam00179  94 LTLEQVLLSIQSLLSEPNPEDPLNAEAAKLYRKNREEFEKKVREYV 139

UBA domain found in a putative ubiquitin conjugating enzyme from plasmodium Yoelii (pyUCE) and similar proteins; P. Yoelii ubiquitin-conjugating enzyme and other uncharacterized family members show high sequence similarity to the human Huntingtin interacting protein-2 (HIP2) which belongs to a class II E2 ubiquitin-conjugating enzyme family. These proteins may play roles in the ubiquitin-mediated protein degradation pathway. They all contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

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gi 914615973 61 KKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:cd14314   3 EKIKKLLEMGFPRDQARKALEKNGWDETLALNTLL 37

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.

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gi 914615973 60 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:cd14307   1 EEAVASLLEMGIPREVAIEALRETNGDVEAAANYIFSN 38

UBA domain found in microtubule-associated protein (MAP)/microtubule affinity-regulating kinase (MARK)/ partitioning-defective 1 (Par-1) and similar proteins; The MARK/Par-1 subfamily contains serine/threonine-protein kinases including mammal MARKs, and polarity kinases Par-1 found in Caenorhabditis elegans and Drosophila melanogaster. Those proteins are frequently found associated with membrane structures and participate in diverse processes from control of the cell cycle and polarity to intracellular signaling and microtubule stability. They are involved in nematode embryogenesis, cell cycle control, epithelial cell polarization, cell signaling, and neuronal migration and differentiation. The mammals MARKs have been implicated in carcinomas, Alzheimer's disease (through tau hyperphosphorylation), and autism. Four MARK isoforms exist in humans. Members in this subfamily contain an N-terminal protein kinase catalytic domain, followed by an ubiquitin-associated (UBA) domain and a C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK).

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gi 914615973 61 KKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:cd14337   4 KRIEIMVSMGFNREEIEESLKNRKFDEVMATYLLL 38

UBA domain found in ubiquitin-associated domain-containing protein 2 (UBAC2) and similar proteins; UBAC2, also called phosphoglycerate dehydrogenase-like protein 1, is a ubiquitin-associated domain (UBA)-domain containing protein encoded by gene UBAC2 (or PHGDHL1), a risk gene for Behcet's disease (BD). It may play an important role in the development of BD through its transcriptional modulation. Members in this family contain an N-terminal rhomboid-like domain and a C-terminal UBA domain.

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gi 914615973 62 KIENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:cd14305   5 QVQQLVDMGFSREDVLEALRQSNNDVNAATNLLL 38

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin conjugating enzyme E2 D1-D3 and related proteins; The E2D family includes mammalian ubiquitin-conjugating enzyme E2 D1-4 (UBE2D1/SFT/UBC5A/UBCH5/UBCH5A, UBE2D2/PUBC1/UBC4/UBC5B/UBCH4/UBCH5B, UBE2D3/UBC5C/UBCH5C, UBE2D4/HBUCE1/UBCH5D), yeast E2 ubiquitin-conjugating enzyme 4 (UBC4) and 5 (UBC5), as well as plant counterpart ubiquitin-conjugating enzyme E2 8-12 (UBC8/UBCAT4A, UBC9/UBCAT4B, UBC10-12) and 28-30 (UBC28-30). They are ubiquitin-conjugating enzymes (EC 2.3.2.23) that accept ubiquitin from the E1 complex and catalyze the covalent attachment to other proteins. In vitro, UBE2D1-3 (EC 2.3.2.23 and EC 2.3.2.24) catalyze 'Lys-48'-linked polyubiquitination. UBE2D3 also catalyzes 'Lys-11'-linked polyubiquitination. In vitro, UBE2D4 can promote polyubiquitination using all 7 ubiquitin Lys residues but may prefer 'Lys-11' and 'Lys-48'-linked polyubiquitination. Saccharomyces cerevisiae UBC4-5 and Arabidopsis thaliana UBC8-11 mediates the selective degradation of short-lived and abnormal proteins.

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gi 914615973  18 EPDDPQDAVVANQYKQNPEMFKQTARLWAHVY 49
Cdd:cd23792  112 NPDDPLVPEIAHLYKTDREKYEATAREWTRKY 143

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.

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gi 914615973 62 KIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:cd14386   5 AVAMLVSMGFTRDQAIKALKATDNNVERAADWIFSH 40

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

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                  ....*....|....*....|....*....|....*....|..
gi 914615973   56 SPEYTKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 97
Cdd:TIGR00601 334 TPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQ 375

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin conjugating enzyme E2 T and related enzymes; The E2T subfamily includes mammalian ubiquitin-conjugating enzymes E2 T (UBE2T/HSPC150/PIG50), plant ubiquitin-conjugating enzyme E2 37 (UBC37), and similar proteins. They are ubiquitin-conjugating enzymes (EC 2.3.2.23) that accept ubiquitin from the E1 complex and catalyze the covalent attachment to other proteins. UBE2T, also called cell proliferation-inducing gene 50 protein, catalyzes monoubiquitination. It is involved in mitomycin-C (MMC)-induced DNA repair. It acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. UBE2T also mediates monoubiquitination of FANCL and FANCI. It may contribute to ubiquitination and degradation of BRCA1. In vitro, UBE2T can promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination.

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gi 914615973   1 MTLRTVLLSLQALLAAAEPDDPQDAVVANQYKQNPEMFKQTARLW 45
Cdd:cd23805   98 LNISTVLTSIRLLLAEPNPDDPLMADIAAEYKYNRALFDAKAKEW 142

UBA domain of AMPK related kinases; The AMPK-RK family comprises AMP-activated protein kinases (AMPKs), MAP/microtubule affinity-regulating kinases (MARKs), Brain-specific kinases (BRSKs), Salt inducible kinases (SIKs), maternal embryonic leucine zipper kinase (MELK), and SNF-related serine/threonine-protein kinase (SNRK). It is the only kinase family in the human genome containing an ubiquitin-associated (UBA) or UBA-like domain which is located immediately C-terminal to their N-terminal protein kinase catalytic domain. In addition, most of family members contain a C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK), but some are lack of this region. AMPK-RKs play central roles in metabolic control, energy homeostasis and stress responses in eukaryotes. They require phosphorylation by liver kinase B1 (LKB1) for full activity. Normally, AMPK-RKs appear to exist as heterotrimeric complexes consisting of a catalytic alpha-subunit and regulatory beta- and gamma-subunits. This model corresponds to the catalytic subunit. The UBA domain, previously called SNF1 homology (SNH) domain, regulates the conformation, LKB1-mediated phosphorylation and activation, and localization of the AMPK-RKs, but does not interact with ubiquitin-like molecules. In AMPKalpha subunits, the UBA-like autoinhibitory domain (AID) is responsible for AMPKalpha subunit autoinhibition. Due to the lack of UBA domain, NUAK1 kinase, also called ARK5 (AMPK-related kinase 5), and NUAK2 kinase, also called SNARK (SNF1/AMPK-related kinase), are not included in this family.

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gi 914615973 63 IENLCAMGFDRNAVIVALSSKSWDVETATELLL 95
Cdd:cd14272   5 LQEMVELGYDREEIVESLRNNRYNDLAATYYLL 37

UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins; HUWE1, also called ARF-binding protein 1 (ARF-BP1), HECT, UBA and WWE domain-containing protein 1, homologous to E6AP carboxyl terminus homologs protein 9 (HectH9), large structure of UREB1 (LASU1), Mcl-1 ubiquitin ligase E3 (Mule), upstream regulatory element-binding protein 1 (URE-B1), or URE-binding protein 1, may function as a ubiquitin-protein ligase that involves in the ubiquitination cascade that targets specific substrate proteins in proteolysis. It can ubiquitylate DNA polymerase beta (Pol beta), the major BER DNA polymerase and modulates base excision repair (BER). HUWE1 also acts as a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF tumor suppressor in p53 regulation. Moreover, HUWE1 is both required and sufficient for the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involving in DNA damage-induced apoptosis. Furthermore, HUWE1 plays an important role in the regulation of Cdc6 stability after DNA damage. In addition, HUWE1 works as a partner of N-Myc oncoprotein in neural cells. It ubiquitinates N-Myc and primes it for proteasomal-mediated degradation. HUWE1 contains a ubiquitin-associated (UBA) domain, a WWE domain, and a Bcl-2 homology region 3 (BH3) domain at the N-terminus and a HECT domain at the C-terminus. WWE domain plays a role in the regulation of specific protein-protein interactions in a ubiquitin conjugation system. BH3 domain is responsible for the specific binding to Mcl-1. HECT domain involves in the inhibition of the transcriptional activity of p53 via a ubiquitin-dependent degradation pathway. It also controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.

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gi 914615973 63 IENLCAMGFDRNAVIVALSSKSwDVETATELLLSN 97
Cdd:cd14288   6 LQQLMDMGFTREHALEALLHTS-TLEQATEYLLTH 39