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.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 914615969 102 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 139
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.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 914615969 102 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 139
Cdd:cd14390    1 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 38

Ubiquitin-conjugating enzyme E2, catalytic domain homologues; Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. This pathway functions in regulating many fundamental processes required for cell viability.TSG101 is one of several UBC homologues that lacks this active site cysteine.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 914615969     8 RIKREFKEVLKSEETSKNQIKVDlvDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPKYKQNPEMF 80
Cdd:smart00212   1 RLLKELKELRKDPPPGFTAYPVD--DENLLEWTGTIVGPPGTPYEGGVFKLTIEFPEDYPFKPPKVKFITKIY 71

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

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 914615969   101 YTKKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 137
Cdd:smart00165   1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYLL 37

Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 914615969   3 NIAVQRIKREFKEVLKSEETSKNqIKVDLVDENFTELRGEIAGP---PDTPYEGGRYQLEIKIPETYPFNPPKYKQNPEM 79
Cdd:COG5078    5 NIRSRRLANDYEELENILARGSW-IHFKATRGNPPKYEVTFNIRgiiRGGPTYGDTHRIEITLPESYPQAPPQVRWLTPI 83

                 .
gi 914615969  80 F 80
Cdd:COG5078   84 F 84

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.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 914615969 102 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 139
Cdd:cd14390    1 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 38

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain/ubiquitin E2 variant (UEV) domain; The family includes ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain and ubiquitin (Ub) E2 variant (UEV) domain. They belong to the ubiquitin-conjugating (UBC) superfamily that represents a structural domain with an alpha-beta(4)-alpha(3) core fold. E2 is part of the ubiquitin-mediated protein degradation pathway in which a thioester linkage forms between a conserved cysteine and the C-terminus of ubiquitin, and complexes with ubiquitin protein ligase enzymes, E3. This pathway regulates many fundamental cellular processes. There are also other E2s which form thioester linkages without the use of E3s. Several UBC homologs (TSG101, Mms2, Croc-1 and similar proteins) contains the UEV domain, which lacks the active site cysteine essential for ubiquitination and appear to function in DNA repair pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 914615969   7 QRIKREFKEVLKSEETSknqIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd00195    1 KRLQKELKELQKNPPPG---ISVEPVDDDLFHWKATIKGPEGTPYEGGVFKLDIEFPDDYPFKPPK 63

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 914615969   7 QRIKREFKEVLKSEEtskNQIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPKYK 74
Cdd:cd23805    1 ARLKRELQLLQKDPP---PGISCWPKDDSLDELEAQIQGPEGTPYEGGVFKLEITIPERYPFEPPKVR 65

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of Saccharomyces cerevisiae Peroxin-4 (PEX4) protein and related proteins; Saccharomyces cerevisiae PEX4 (EC 2.3.2.23), also called ubiquitin-conjugating enzyme E2-21 kDa, UBC10, or PAS2, acts as a ubiquitin-conjugating enzyme that catalyzes the covalent attachment of ubiquitin to other proteins. It is essential for peroxisome biogenesis and is required for UBC4-independent ubiquitination of PEX5. This subfamily also includes Arabidopsis thaliana PEX4 (also known as UBC21, EC 2.3.2.23) that is required for peroxisome biogenesis. It is necessary for the developmental elimination of obsolete peroxisome matrix proteins. It may be involved in the ubiquitination of PEX5, targeting it for recycling.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 914615969   7 QRIKREFKEVLKSEetskNQIKVDLV---DENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPKYK 74
Cdd:cd23812    1 KRLLKELRELQKEP----NDPDIVLGpveDDDLFRWEAVIKGPKDTPYEGGRFELAIQVPSNYPISPPKVK 67

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin conjugating enzyme E2 S and related domains; The E2S subfamily includes mammalian ubiquitin-conjugating enzymes E2 S (UBE2S/E2EPF), plant ubiquitin-conjugating enzyme E2 22 (UBC22), and similar proteins. They are ubiquitin-conjugating enzymes (EC2.3.2.23) that accept ubiquitin from the E1 complex and catalyze the covalent attachment to other proteins. UBE2S catalyzes 'Lys-11'-linked polyubiquitination. It acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. UBE2S acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit. It also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as an E2 enzyme for the APC/C in vivo. UBE2S is also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A. In vitro, it can promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 914615969   5 AVQRIKREFKEVLKSEEtskNQIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23804    3 VIRRLAKELQSLQSNPP---EGIRVIPNEEDLTDIQAEIEGPEGTPYEGGVFRVKLVLGPDFPASPPK 67

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 J1, J2 and related proteins; The E2J subfamily includes mammalian ubiquitin-conjugating enzymes E2 J1 (UBE2J1/HSPC153/HSPC205/NCUBE1) and J2 (UBE2J2/NCUBE1), yeast ubiquitin-conjugating enzyme E2 6 (UBC6/DOA2), and plant ubiquitin-conjugating enzyme E2 32-34 (UBC32-34). 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. UBE2J1 and UBE2J2 are non-canonical ubiquitin-conjugating enzyme (NCUBE), which function in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD). Saccharomyces cerevisiae UBC6 functions in degradation of misfolded or regulated proteins localized in the endoplasmic reticulum (ER) lumen or membrane via the ubiquitin-proteasome system. It is a cognate E2 conjugating enzyme for the DOA10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 914615969   7 QRIKREFKEVLKSEEtskNQIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPP 71
Cdd:cd23799    1 KRLLKELRELQKDPP---PYIVAAPLEDNILEWHFTIRGPPDTPYEGGIYHGKIVFPPDYPFKPP 62

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin conjugating enzyme E2 W and related enzymes; The E2W subfamily includes mammalian ubiquitin-conjugating enzymes E2 W (UBE2W/UBC16), plant ubiquitin-conjugating enzyme E2 15-18 (UBC15-18), 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. UBE2W, also called FLJ11011, E2 ubiquitin-conjugating enzyme W, N-terminal E2 ubiquitin-conjugating enzyme (EC 2.3.2.25), N-terminus-conjugating E2, ubiquitin carrier protein W, ubiquitin-conjugating enzyme 16 (UBC-16), or ubiquitin-protein ligase W, specifically monoubiquitinates the N-terminus of various substrates, including ATXN3, MAPT/TAU, POLR2H/RPB8 and STUB1/CHIP, by recognizing backbone atoms of disordered N-termini. In vitro, UBE2W catalyzes 'Lys-11'-linked polyubiquitination. UBE2W is an important protein for early postnatal survival and for the normal functioning of multiple organ systems.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 914615969   8 RIKREFKEVLKSEETsknQIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPP 71
Cdd:cd23808    3 RLQKELKELQKNPPP---GITLDVADNNLTEWIVTIEGAPGTLYEGEKFRLRFKFPPDYPIESP 63

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 G1 and related proteins; The subfamily includes mammalian ubiquitin-conjugating enzymes E2 G1 (UBE2G1/UBC7/E217K), fission yeast ubiquitin-conjugating enzyme E2 15 (UBC15), plant ubiquitin-conjugating enzymes E2 7 (UBC7), E2 13 (UBC13) and E2 14 (UBC14). 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, UBE2G1 catalyzes 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. It may be involved in the degradation of muscle-specific proteins and may mediate polyubiquitination of CYP3A4. Schizosaccharomyces pombe UBC15 has a role in the formation of chromatin structures that influence the localization of transcriptional silencing factors. Arabidopsis thaliana UBC7, UBC13 and UBC14 are involved in the formation of multiubiquitin chains. They signal the protein for selective degradation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 914615969   5 AVQRIKREFKEVlkseetSKNQI---KVDLVDE-NFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPKYKQNPEMF 80
Cdd:cd23795    2 AALLLRKQLKEL------QKNPVegfSAGLVDDsNIYEWEVMIIGPPDTLYEGGFFKAELTFPDDYPNSPPKMKFITEMW 75

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 N and related proteins; The E2N subfamily includes mammalian ubiquitin-conjugating enzymes E2 N (UBE2N/UBCH13/UBC13/BLU), yeast ubiquitin-conjugating enzyme E2 13 (UBC13), and plant ubiquitin-conjugating enzyme E2 35-36 (UBC35/UBC13A/UBG13A, UBC36/UBC13B/UBG13B), which function as ubiquitin-conjugating enzymes (EC 2.3.2.23). UBE2N, also called Bendless-like ubiquitin-conjugating enzyme, forms heterodimers with UBE2V1 and UBE2V2, respectively. The UBE2V1/UBE2N and UBE2V2/UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. UBE2N also plays a role in the control of progress through the cell cycle and differentiation, as well as in the error-free DNA repair pathway, and contributes to the survival of cells after DNA damage. Saccharomyces cerevisiae UBC13 has a role in the DNA error-free post-replication repair (PRR) pathway. The UBC13/MMS2 heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. Arabidopsis thaliana UBC35 and UBC36 catalyze the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. They mediate transcriptional activation of target genes. They are required for post-replication repair of UV-damaged DNA and for adapting root developmental programs to suboptimal availability of iron.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 914615969  10 KREFKEVLKSEETSKNQIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23813    3 RRIIKETQRLLAEPVPGISATPDEDNLRYFDVVIDGPPDSPYEGGVFKLELFLPEEYPMAPPK 65

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of Acanthamoeba polyphaga mimivirus bifunctional E2/E3 enzyme R795 and related proteins; R795 (EC 2.3.2.23/EC 2.3.2.27) is a bifunctional enzyme which acts as an E2 ubiquitin-conjugating enzyme that catalyzes the covalent attachment of ubiquitin to other proteins. It also acts as a RING-type E3 ubiquitin-protein transferase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 914615969   7 QRIKREFKEVLKSEETSknqIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPP 71
Cdd:cd23833    1 RRILRELRSLLKNPHPN---IDVYPSEEDIGFWKVLMEGPEGTPYEGGVFLLYVEFPEEYPVKPP 62

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of Saccharomyces cerevisiae CDC34 and related proteins; Saccharomyces cerevisiae CDC34 (EC 2.3.2.23), also called ubiquitin-conjugating enzyme E2-34 kDa, cell division control protein 34, E2 ubiquitin-conjugating enzyme 3 (UBC3), DNA6, or ubiquitin ligase complex SCF subunit CDC34, catalyzes the covalent attachment of ubiquitin to other proteins. In vitro, it may ubiquitinate histone H2A. CDC34 mediates the initiation of DNA replication (transition of G1 to S phase in cell cycle). It is the catalytic subunit of an SCF ubiquitin-protein ligase complex (together with Skp1p, Rbx1p, CDC53, and an F-box protein) that regulates cell cycle progression by targeting key substrates for degradation. Moreover, CDC34 is involved in the regulation of methionine biosynthesis genes and in the degradation of CDC6 together with CDC4 and CDC53.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 914615969   5 AVQRIKREFKEVlkSEETSKNQIKVDLVDEN-FTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPKYKQNPEMF 80
Cdd:cd23811    1 AAKILMKEYKEL--TKPKTGPWVHIELVNDNiFTWTVGLMVLNPDSIYNGGYFKAEMVFPRDYPFSPPSFRFLPPIF 75

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzymes E2A, E2B and related proteins; The E2A/2B subfamily includes mammalian ubiquitin-conjugating enzymes UBE2A/RAD6A and UBE2B/RAD6B, yeast ubiquitin-conjugating enzyme E2 2 (UBC2/RAD6), plant ubiquitin-conjugating enzyme E2 1-3 (UBC1-3), 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. Both UBE2A/RAD6A and UBE2B/RAD6B are required for post-replication repair of UV-damaged DNA. In vitro, they catalyze 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. UBE2B might also catalyze 'Lys-63'-linked polyubiquitination. Saccharomyces cerevisiae UBC2 is required for DNA repair, damage-induced mutagenesis, and sporulation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 914615969   5 AVQRIKREFKEVLKSEETSknqIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPKYKQNPEMF 80
Cdd:cd23790    3 ARRRLMRDFKRLQKDPPEG---ISAAPVEDNIMVWNAVIFGPEDTPWEGGTFKLRLEFSEEYPNKPPKVRFVSKMF 75

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

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 914615969   101 YTKKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 137
Cdd:smart00165   1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYLL 37

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 914615969   8 RIKREFKEVLKSEETsknQIKVDLVDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23792    3 RINKELQDLGRDPPA---NCSAGPVGDDLFHWQATIMGPPDSPYQGGVFFLNIHFPTDYPFKPPK 64

ubiquitin-conjugating enzyme family protein; This subfamily includes ubiquitin-conjugating enzyme E2, catalytic (UBCc) domains mostly found in non-vertebrate eukaryotes. They belong to the ubiquitin-conjugating (UBC) superfamily that represents a structural domain with an alpha-beta(4)-alpha(3) core fold. E2 is part of the ubiquitin-mediated protein degradation pathway in which a thioester linkage forms between a conserved cysteine and the C-terminus of ubiquitin and complexes with ubiquitin protein ligase enzymes, E3. This pathway regulates many fundamental cellular processes. There are also other E2s which form thioester linkages without the use of E3s.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 914615969   8 RIKREFKEVLKSEETsknQIKVDLVDENFTELRGEIAGPPDtPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23955    2 RLLRDLKELQEEPLP---GVSAEPLENDLFEWHVNIRGPDG-PYSGVILHLELTFPEDYPNSPPS 62

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 I and related proteins; The E2I subfamily includes mammalian ubiquitin-conjugating enzymes E2 I (UBE2I/UBC9/UBCE9, EC 2.3.2.-), yeast ubiquitin-conjugating enzyme E2-18 kDa (UBC9, EC2.3.2.-), and plant SUMO-conjugating enzyme 1 (SCE1/AHUS5, EC2.3.2.-). UBE2I, also called SUMO-conjugating enzyme UBC9, RING-type E3 SUMO transferase UBC9, SUMO-protein ligase, ubiquitin carrier protein 9, ubiquitin carrier protein I, or ubiquitin-protein ligase I, accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. It can catalyze the formation of poly-SUMO chains. It is necessary for sumoylation of FOXL2 and KAT5 and essential for nuclear architecture and chromosome segregation. UBE2I also sumoylates p53/TP53 at 'Lys-386' and mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity. Saccharomyces cerevisiae UBC9, also called SUMO-conjugating enzyme UBC9, RING-type E3 SUMO transferase UBC9, ubiquitin carrier protein 9, ubiquitin-conjugating enzyme E2-18 kDa, acts as an E2 ubiquitin-like--protein ligase that mediates SUMO/Smt3 attachment to septins and PCNA. It may be involved in degradation of S- (CLB5) and M-phase cyclins (CLB2). Arabidopsis thaliana SCE1, also called SUMO-conjugating enzyme SCE1, protein EMBRYO DEFECTIVE 1637, or protein hus5 homolog, is a SUMO-conjugating enzyme that accepts the SUMO proteins from the E1 SUMO-activating heterodimer SAE1/SAE2 and catalyzes its covalent attachment to other proteins with the E3 SUMO ligases SIZ1 and MMS21. It associates with SIZ1 for sumoylation of the transcription factor GTE3.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 914615969  43 IAGPPDTPYEGGRYQLEIKIPETYPFNPPKYKQNPEMF 80
Cdd:cd23798   42 IPGKKGTPWEGGLYKLTMEFPEDYPSKPPKCKFDPPLF 79

Ubiquitin-conjugating enzyme E2, catalytic (UBCc)-like domain of baculoviral IAP repeat-containing protein 6 (BIRC6) and related proteins; BIRC6, also BIR repeat-containing ubiquitin-conjugating enzyme (BRUCE), RING-type E3 ubiquitin transferase (EC 2.3.2.27) BIRC6, or ubiquitin-conjugating BIR domain enzyme apollon (APOLLON), is an anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. It has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its targets include CASP9 and DIABLO/SMAC. BIRC6 acts as an inhibitor of CASP3, CASP7, and CASP9. BIRC6 is an important regulator for the final stages of cytokinesis. It is crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 914615969   7 QRIKREFKEV------LKSEETSKNQIKVDlvDENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23810    2 ARMRRLAKELaslstsLPLSWSSSIFVRVD--EERMDVMKALITGPEDTPYANGCFLFDIFFPPDYPQSPPK 71

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 O and related proteins; The E2O subfamily includes mammalian ubiquitin-conjugating enzymes E2 O (UBE2O, EC 2.3.2.24), plant ubiquitin-conjugating enzyme E2 23-26 (UBC23-26, EC2.3.2.23) and E2 38-39 (UBC38-39, EC2.3.2.23), and similar proteins. UBE2O is an E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins. Arabidopsis thaliana UBC proteins accept the ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. UBC24, also called PHO2, mediates PHO1 degradation through multivesicular body-mediated vacuolar proteolysis in response to inorganic phosphate (Pi) availability. It negatively regulates the protein abundance of PHF1 and PHT1s under Pi-sufficient conditions by facilitating the degradation of PHT1 proteins at the endomembrane.

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gi 914615969  39 LRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23837   34 LRALIVGPEGTPYEDGLFFFDIQLPPDYPNVPPK 67

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 U and related proteins; The E2U subfamily includes mammalian ubiquitin-conjugating enzymes E2 U (UBE2U/, EC 2.3.2.23) and similar proteins. They are ubiquitin-conjugating enzymes that accept ubiquitin from the E1 complex and catalyze the covalent attachment to other proteins.

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gi 914615969   9 IKREFkevLKSEETSKNQIKVDLV-DENFTELRGEIAGPPDTPYEGGRYQLEIKIPETYPFNPP 71
Cdd:cd23806    3 LEREL---LELQENPLWGIEAKPVsDDNLFEWTAKIKGLKDTIWEGGIFRLTLKFSENYNYVPP 63

Ubiquitin-conjugating enzyme E2, putative catalytic (UBCc) domain of Trypanosoma cruzi putative ubiquitin-conjugating enzyme E2 and related proteins; This subfamily includes uncharacterized Trypanosoma cruzi putative ubiquitin-conjugating enzyme E2 and similar proteins. They may function as ubiquitin-conjugating enzymes (EC 2.3.2.23) that accept ubiquitin from the E1 complex and catalyze the covalent attachment to other proteins.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 914615969   8 RIKREFKEVLKSEETSKNQIK----VDLVD-ENFTELRGEIAGPPDT-PYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23828    2 RIGKDLRLLLESIKTGTEVDPagslIASVDsDSLFHWRVVVKPPANSiVYAGNTYELLVIFSDDYPHEPPK 72

UBA domain found in Saccharomyces cerevisiae DNA-damage response protein Ddi1 and similar proteins; Ddi1, also called v-SNARE-master 1 (Vsm1), is a ubiquitin receptor involved in regulation of the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as a ubiquitin association domain (UBA)- ubiquitin-like-domain (UBL) shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. Ddi1 contains an N-terminal UBL domain and a C-terminal UBA domain. It also harbors a central retroviral aspartyl-protease-like domain (RVP) which may be important in cell-cycle control. At this point, Ddi1 may function proteolytically during regulated protein turnover in the cell. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also called transporter regulator RS1 (RS1) which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1.

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gi 914615969 104 KIENLCAMGFDRNAVIVALSSKSWDVETATELLL 137
Cdd:cd14309    3 KIAQLMDLGFSREEAIQALEATNGNVELAASLLF 36

ubiquitin E2 variant (UEV) domain of ubiquitin-conjugating enzyme E2 variant 1, 2 and related proteins; The E2V subfamily includes mammalian ubiquitin-conjugating enzyme E2 variant 1 (UBE2V1/CROC1/UBE2V/UEV1) and variant 2 (UBE2V2/MMS2/UEV2), yeast ubiquitin-conjugating enzyme variant MMS2, plant ubiquitin-conjugating enzyme E2 variant 1A (UEV1A/MMZ1) and variant 1B (UEV1B/MMZ2), and similar proteins. They have no ubiquitin ligase activity on their own. UBE2V1 (also called UEV-1, CROC-1, or TRAF6-regulated IKK activator 1 beta Uev1A) and UBE2V2 (also called DDVit 1, enterocyte differentiation-associated factor 1 (EDAF-1), enterocyte differentiation-promoting factor 1 (EDPF-1), MMS2 homolog, or vitamin D3-inducible protein) form heterodimers with UBE2N, respectively. Saccharomyces cerevisiae UEV MMS2 has a role in the DNA error-free postreplication repair (PRR) pathway. It forms a heterodimer with UBC13. Arabidopsis thaliana UEV1A and UEV1A form heterodimers with UBC35 or UBC36. The heterodimers possess ubiquitin-conjugating enzyme (EC 2.3.2.23) activity, catalyzing the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Members of this subfamily may mediate transcriptional activation of target genes and plays a role in the control of progress through the cell cycle and differentiation. UEVs are homologous to E2 ubiquitin ligases but lack the conserved cysteine residue required for catalytic activity.

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gi 914615969  40 RGEIAGPPDTPYEGGRYQLEIKIPETYPFNPPK 72
Cdd:cd23807   41 NGTIIGPPGTVFENRIYSLKIECGENYPDEPPT 73

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 914615969 103 KKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 137
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 914615969 102 TKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 139
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 914615969 103 KKIENLCAMGFDRNAVIVALSSKSWDVETATELLL 137
Cdd:cd14337    4 KRIEIMVSMGFNREEIEESLKNRKFDEVMATYLLL 38

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.

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                 ....*....|....*....|....*....|..
gi 914615969 105 IENLCAMGFDRNAVIVALSSKSWDVETATELL 136
Cdd:cd14287    4 VQSLVAMGFEKHRARRALDAAGGDINTAVEIL 35

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 914615969   98 SPEYTKKIENLCAMGFDRNAVIVALSSKSWDVETATELLLSN 139
Cdd:TIGR00601 334 TPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQ 375

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 914615969 105 IENLCAMGFDRNAVIVALSSKSwDVETATELLLSN 139
Cdd:cd14288    6 LQQLMDMGFTREHALEALLHTS-TLEQATEYLLTH 39

UBA domain found in plant ubiquitin-conjugating enzyme E2 27 and similar proteins; UBC27, also called ubiquitin carrier protein 27, functions as a class II ubiquitin-conjugating (UBC) enzyme (E2). E2, together with E1 (ubiquitin-activating enzyme UBA) and E3 (ubiquitin ligase), is required in the multi-step reaction of ubiquitin conjugation. Unlike other Arabidopsis UBCs, in addition to an N-terminal ubiquitin-conjugating enzyme E2 catalytic domain (UBCc), UBC27 has an additional C-terminal ubiquitin-associated domain (UBA).

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                 ....*....|....*....|....*....|....
gi 914615969 104 KIENLCAMGFDRNAVIVALSSKSWDVETATELLL 137
Cdd:cd14312    3 KVQRLVEMGFPRDQAVVALESAGGDENAALEKLL 36