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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  11 RLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSGPWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNLF-GSYI 89
Cdd:cd23955    2 RLLRDLKELQEEPLPGVSAEPLENDLFEWHVNIRGPDGPYSGVILHLELTFPEDYPNSPPSV-RLLTPLPHPNVFtGNYI 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 170089135  90 CCDLLKPQTSYHyGTGYTgGYSPALTLRGLFLQFLTFF 127
Cdd:cd23955   81 CLDMLENFAKHH-SKPYS-GWSPAYTVQSILLQLQAFL 116

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  11 RLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSGPWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNLF-GSYI 89
Cdd:cd23955    2 RLLRDLKELQEEPLPGVSAEPLENDLFEWHVNIRGPDGPYSGVILHLELTFPEDYPNSPPSV-RLLTPLPHPNVFtGNYI 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 170089135  90 CCDLLKPQTSYHyGTGYTgGYSPALTLRGLFLQFLTFF 127
Cdd:cd23955   81 CLDMLENFAKHH-SKPYS-GWSPAYTVQSILLQLQAFL 116

ubiquitin-conjugating enzyme; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  11 RLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSG-PWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNL--FGS 87
Cdd:PTZ00390   6 RIEKETQNLANDPPPGIKAEPDPGNYRHFKILMEGPDGtPYEGGYYKLELFLPEQYPMEPPKV-RFLTKIYHPNIdkLGR 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170089135  88 yICCDLLKPQtsyhygtgytggYSPALTLRGLFLQFLTFFSSTkvEQDyggDPVE--IGDHILTNyMKESEMVQRS 161
Cdd:PTZ00390  85 -ICLDILKDK------------WSPALQIRTVLLSIQALLSAP--EPD---DPLDtsVADHFKNN-RADAEKVARE 141

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  11 RLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSGPWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNLF-GSYI 89
Cdd:cd23955    2 RLLRDLKELQEEPLPGVSAEPLENDLFEWHVNIRGPDGPYSGVILHLELTFPEDYPNSPPSV-RLLTPLPHPNVFtGNYI 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 170089135  90 CCDLLKPQTSYHyGTGYTgGYSPALTLRGLFLQFLTFF 127
Cdd:cd23955   81 CLDMLENFAKHH-SKPYS-GWSPAYTVQSILLQLQAFL 116

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135   11 RLYQDLAELHENPYPGVVVFTDDANLRKF-CLVLVPPSGPWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNLF--GS 87
Cdd:pfam00179   1 RLQKELKELLKDPPPGISAGPVDDNLFEWkVTIIGPDGTPYEGGVFKLSVEFPEDYPFKPPKV-KFTTKIYHPNVDssGE 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 170089135   88 yICCDLLKPQTsyhygtgytggYSPALTLRG--LFLQFL 124
Cdd:pfam00179  80 -VCLDILKDER-----------WSPALTLEQvlLSIQSL 106

ubiquitin-conjugating enzyme; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  11 RLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSG-PWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNL--FGS 87
Cdd:PTZ00390   6 RIEKETQNLANDPPPGIKAEPDPGNYRHFKILMEGPDGtPYEGGYYKLELFLPEQYPMEPPKV-RFLTKIYHPNIdkLGR 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170089135  88 yICCDLLKPQtsyhygtgytggYSPALTLRGLFLQFLTFFSSTkvEQDyggDPVE--IGDHILTNyMKESEMVQRS 161
Cdd:PTZ00390  85 -ICLDILKDK------------WSPALQIRTVLLSIQALLSAP--EPD---DPLDtsVADHFKNN-RADAEKVARE 141

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  10 SRLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSG-PWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNL--FG 86
Cdd:cd23805    1 ARLKRELQLLQKDPPPGISCWPKDDSLDELEAQIQGPEGtPYEGGVFKLEITIPERYPFEPPKV-RFLTPIYHPNIdsAG 79

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 170089135  87 SyICCDLLKPQTSyhygtgytGGYSPALTLRGLFLQ 122
Cdd:cd23805   80 R-ICLDILKMPPK--------GSWKPSLNISTVLTS 106

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135   8 LLSRLYQDLAELHENPYPGVVVFTDDANLRKF-CLVLVPPSGPWKDLALHFDVELPEQWPSSPPRiassVH---DIDHPN 83
Cdd:cd23813    1 LPRRIIKETQRLLAEPVPGISATPDEDNLRYFdVVIDGPPDSPYEGGVFKLELFLPEEYPMAPPK----VRfltKIYHPN 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 170089135  84 L--FGSyICCDLLKPQtsyhygtgytggYSPALTLRGLFL 121
Cdd:cd23813   77 IdkLGR-ICLDILKDK------------WSPALQIRTVLL 103

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 L3, L5, L6 and related proteins; The E2L3-like subfamily includes mammalian ubiquitin-conjugating enzymes E2 L3 (UBE2L3/UBCH7/UBCE7), L5 (UBE2L5), L6 (UBE2L6/UBCH8), 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. UBE2L3 specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. It does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN and ARIH1, that function like RING-HECT hybrids. In vitro, UBE2L3 catalyzes 'Lys-11'-linked polyubiquitination. It is involved in the selective degradation of short-lived and abnormal proteins. In addition to ubiquitin, UBE2L6 also catalyzes the covalent attachment of ISG15 to other proteins. It functions in the E6/E6-AP-induced ubiquitination of p53/TP53. It promotes ubiquitination and subsequent proteasomal degradation of FLT3.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 170089135  11 RLYQDLAELHENPYPGV-VVFTDDANLRKFCLVLVPPSGPWKDLALHFDVELPEQWPSSPPRIA--SSVHdidHPN 83
Cdd:cd23801    4 RLQKELEELRKSGPKYFrDLSVDESNVLKWTGLLVPDNPPYNKGAFRIEITFPAEYPFKPPKITfkTKIY---HPN 76

ubiquitin E2 variant (UEV) domain of AKT-interacting protein and related proteins; AKTIP, also called Ft1, or fused toes protein homolog, is a component of the FTS/Hook/FHIP complex (FHF complex), which may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). AKTIP regulates apoptosis by enhancing phosphorylation and activation of AKT1. It increases release of TNFSF6 via the AKT1/GSK3B/NFATC1 signaling cascade. AKTIP contains a UEV domain that is homologous to E2 ubiquitin ligases but lacks the conserved cysteine residue required for catalytic activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 170089135  11 RLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSGPWKDLALHFDVELPEQWPSSPPRI--ASSVHdidHP 82
Cdd:cd23814    2 ELLAEYKLLREQPPPGVYVLPSAENPLLWHGVIFVRSGLYKGGIFRFTISIPDNYPDGPPRVtfLSPVF---HP 72

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  10 SRLYQDLAELHENPYPGVVVFT--DDANLRKFCLVLVPPSG-PWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPNL-F 85
Cdd:cd23812    1 KRLLKELRELQKEPNDPDIVLGpvEDDDLFRWEAVIKGPKDtPYEGGRFELAIQVPSNYPISPPKV-KFVTKIFHPNVhF 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 170089135  86 --GSyICCDLLKPQtsyhygtgytggYSPALTL 116
Cdd:cd23812   80 ktGE-ICLDILKTA------------WSPAWTL 99

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 C and related proteins; The E2C family includes mammalian ubiquitin-conjugating enzyme E2 C (UBE2C/UBCH10), yeast E2 ubiquitin-conjugating enzyme 11 (UBC11), plant ubiquitin-conjugating enzyme E2 19 (UBC19) and 20 (UBC20). 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. UBE2C, also known as (E3-independent) E2 ubiquitin-conjugating enzyme C (EC 2.3.2.24), E2 ubiquitin-conjugating enzyme C, ubiquitin carrier protein C, or ubiquitin-protein ligase C, catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination in vitro. It is a ubiquitin carrier protein required for the destruction of mitotic cyclins and proteins that maintain sister chromatid cohesion in animal cells and in Schizosaccharomyces pombe. In Saccharomyces cerevisiae, UBC11 is not essential for mitotic cyclin destruction. Arabidopsis thaliana UBC19 is part of the anaphase-promoting complex (APC). It may have a key function during cell cycle and be involved in cyclin B1 degradation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  10 SRLYQDLAELHENPYPGVVVFTDDANLRKFCLVLVPPSG-PWKDLALHFDVELPEQWPSSPPRIaSSVHDIDHPN--LFG 86
Cdd:cd23791    2 KRLQSELMTLMMSGDPGISAFPDGDNLFKWIGTITGPEGtVYEGLKYKLSLEFPSNYPYKAPTV-KFETPCFHPNvdQHG 80

                 ....*....
gi 170089135  87 SyICCDLLK 95
Cdd:cd23791   81 N-ICLDILK 88

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 H and related proteins; The E2H subfamily includes mammalian ubiquitin-conjugating enzymes E2 H (UBE2H), yeast E2 ubiquitin-conjugating enzyme 8 (UBC8/GID3), and plant ubiquitin-conjugating enzyme E2 4-6 (UBC4-6). 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. UBE2H (also E3-independent, EC 2.3.2.24) transfers ubiquitin to MAEA, a core component of the CTLH E3 ubiquitin-protein ligase complex. In vitro, UBE2H catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. It might also ubiquitinate histone H2A. Saccharomyces cerevisiae UBC8 is required for the adaptation to the presence of glucose in the growth medium; it mediates the degradation of enzymes involved in gluconeogenesis when cells are shifted to glucose-containing medium. It is also required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170089135  11 RLYQDLAELHENPYPgvvVFTDDANLRKFCLVLVPPS------GPWKdlaLHfdVELPEQWPSSPPRIAsSVHDIDHPN- 83
Cdd:cd23797    2 RIETDVMKLMMSDYE---VTLLNDSMNEFIVKFHGPKdtpyegGVWK---VR--VELPDDYPYKSPSIG-FVNKIFHPNi 72

                         90
                 ....*....|....*..
gi 170089135  84 --LFGSyICCDLLKpQT 98
Cdd:cd23797   73 deASGS-VCLDVIN-QT 87