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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4512 AARARRLAQEAVTLSTSLPLSSSSSVFVRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGH 4591
Cdd:cd23810      1 PARMRRLAKELASLSTSLPLSWSSSIFVRVDEERMDVMKALITGPEDTPYANGCFLFDIFFPPDYPQSPPKVNLLTTGGG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4592 SVRFNPNLYNDGKVCLSILNTWHGRPEEKWNPQTSSFLQVLVSVQSLILVAEPYFNEPGYERSRGTPSGTQSSREYDGNI 4671
Cdd:cd23810     81 SVRFNPNLYNDGKVCLSLLGTWSGPPGEKWNPGTSTLLQVLVSIQSLILVPEPYFNEPGYERSRGTPEGDAASREYNANI 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 2217329837 4672 RQATVKWAMLEQIRNPSPCFKEVIHKHFYLKRVEIMAQCEEWIAD 4716
Cdd:cd23810    161 RYNTVRWAMLEQLRNPPPGFEDVIRTHFYLKREEILAQCEKWIAE 205

Inhibitor of Apoptosis domain; BIR stands for 'Baculovirus Inhibitor of apoptosis protein Repeat'. It is found repeated in inhibitor of apoptosis proteins (IAPs), and in fact it is also known as IAP repeat. These domains characteriztically have a number of invariant residues, including 3 conserved cysteines and one conserved histidine that coordinate a zinc ion. They are usually made up of 4-5 alpha helices and a three-stranded beta-sheet. BIR is also found in other proteins known as BIR-domain-containing proteins (BIRPs), such as Survivin.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217329837  289 RRETFTSWPHVGYRWAQPDPMAQAGFYHQPAssgDDRAMCFTCSVCLVCWEPTDEPWSEHERHSPNCPFVK 359
Cdd:pfam00653    1 RLATFENWPHSNKSPPTPEELAEAGFYYTGT---GDRVQCFYCGLELDGWEEGDDPWEEHKKHSPDCPFLK 68

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4512 AARARRLAQEAVTLSTSLPLSSSSSVFVRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGH 4591
Cdd:cd23810      1 PARMRRLAKELASLSTSLPLSWSSSIFVRVDEERMDVMKALITGPEDTPYANGCFLFDIFFPPDYPQSPPKVNLLTTGGG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4592 SVRFNPNLYNDGKVCLSILNTWHGRPEEKWNPQTSSFLQVLVSVQSLILVAEPYFNEPGYERSRGTPSGTQSSREYDGNI 4671
Cdd:cd23810     81 SVRFNPNLYNDGKVCLSLLGTWSGPPGEKWNPGTSTLLQVLVSIQSLILVPEPYFNEPGYERSRGTPEGDAASREYNANI 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 2217329837 4672 RQATVKWAMLEQIRNPSPCFKEVIHKHFYLKRVEIMAQCEEWIAD 4716
Cdd:cd23810    161 RYNTVRWAMLEQLRNPPPGFEDVIRTHFYLKREEILAQCEKWIAE 205

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 2217329837 4542 DEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETtgghsVRFNPNLYNDGKVCLSILNTWHgrpeekW 4621
Cdd:pfam00179   22 VDDNLFEWKVTIIGPDGTPYEGGVFKLSVEFPEDYPFKPPKVKFTT-----KIYHPNVDSSGEVCLDILKDER------W 90

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2217329837 4622 NPqTSSFLQVLVSVQSLIlvAEPYfNEPGYERSRGTPSGtQSSREYDGNIRQAT 4675
Cdd:pfam00179   91 SP-ALTLEQVLLSIQSLL--SEPN-PEDPLNAEAAKLYR-KNREEFEKKVREYV 139

Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217329837  287 ANRRETFTSWPHvgYRWAQPDPMAQAGFYHQPAssgDDRAMCFTCSVCLVCWEPTDEPWSEHERHSPNCPFVKG 360
Cdd:cd00022      1 EARLKTFKNWPI--SLKVTPEKLAEAGFYYTGR---GDEVKCFFCGLELKNWEPGDDPWEEHKRWSPNCPFVLL 69

Baculoviral inhibition of apoptosis protein repeat; Domain found in inhibitor of apoptosis proteins (IAPs) and other proteins. Acts as a direct inhibitor of caspase enzymes.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217329837   285 SEANRRETFTSWPHVgyrwAQPDP--MAQAGFYHQPASsgdDRAMCFTCSVCLVCWEPTDEPWSEHERHSPNCPFVKG 360
Cdd:smart00238    1 SEEARLKTFQNWPYN----SKCTPeqLAEAGFYYTGVG---DEVKCFFCGGELDNWEPGDDPWEEHKKWSPNCPFVRN 71

Ribosome Biogenesis Protein Nsa1; Ribosome biogenesis protein Nsa1 (Nop7-associated 1) from fungi is an essential factor for ribosome assembly. In cooperation with the assembly factor Rix7, Nsa1 participates in an early cleavage of the pre-rRNA processing pathway. Rix7 is a type II double ring, AAA-ATPase, that may mediate the release of Nsa1 from nucleolar pre-60S particles. The release of Nsa1 from a discrete preribosomal particle may trigger the progression of 60S ribosome biogenesis. Nsa1 is essential for cell viability in yeast. It contains an N-terminal seven-bladed beta-propeller WD40 domain that associates with the D1-AAA domain of the AAA-ATPase Rix7, and a flexible lysine-rich C-terminus that extends outward from the WD40 domain, and is required for nucleolar localization.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837  901 GHLVITT-QGGYVKILDLS--------NFEILAKVEPPKKEGTEEQDTFVSVIYCSGTDRLCACTKGGELHFLQIGGTCD 971
Cdd:cd22858     56 EKLLVARrLNGSVELYDLSkvpkfdeeEYELLHSIKGLLDDRSKAKDKFVSLIVLESLGIILAATKSGLVHIIDLEDDLF 135

                   ...
gi 2217329837  972 DID 974
Cdd:cd22858    136 KIK 138

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4512 AARARRLAQEAVTLSTSLPLSSSSSVFVRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGH 4591
Cdd:cd23810      1 PARMRRLAKELASLSTSLPLSWSSSIFVRVDEERMDVMKALITGPEDTPYANGCFLFDIFFPPDYPQSPPKVNLLTTGGG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4592 SVRFNPNLYNDGKVCLSILNTWHGRPEEKWNPQTSSFLQVLVSVQSLILVAEPYFNEPGYERSRGTPSGTQSSREYDGNI 4671
Cdd:cd23810     81 SVRFNPNLYNDGKVCLSLLGTWSGPPGEKWNPGTSTLLQVLVSIQSLILVPEPYFNEPGYERSRGTPEGDAASREYNANI 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 2217329837 4672 RQATVKWAMLEQIRNPSPCFKEVIHKHFYLKRVEIMAQCEEWIAD 4716
Cdd:cd23810    161 RYNTVRWAMLEQLRNPPPGFEDVIRTHFYLKREEILAQCEKWIAE 205

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4537 VFVRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVN-LETTGGhsvRFNPNLYNDGKVCLSILNTWHG 4615
Cdd:cd23837     22 IFVRAYEDRMDLLRALIVGPEGTPYEDGLFFFDIQLPPDYPNVPPKVHyHSWTGG---RLNPNLYEDGKVCLSLLGTWSG 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4616 RPEEKWNPQTSSFLQVLVSVQSLILVAEPYFNEPGYERSRGTPSGTQSSREYDGNIRQATVKwAMLEQIRNPSPCFKEVI 4695
Cdd:cd23837     99 KGTEKWTPKSSNLLQVLVSIQGLVLVKEPYYNEAGYDKQRGTQEGRENSRMYNEMAFLLSLQ-SMLHLLRNPPEGFEDEI 177

                          170       180
                   ....*....|....*....|.
gi 2217329837 4696 HKHFYLKRVEIMAQCEEWIAD 4716
Cdd:cd23837    178 RSHFRKRGPRLLARLEAWLEG 198

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 2217329837 4542 DEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETtgghsVRFNPNLYNDGKVCLSILNTWHgrpeekW 4621
Cdd:pfam00179   22 VDDNLFEWKVTIIGPDGTPYEGGVFKLSVEFPEDYPFKPPKVKFTT-----KIYHPNVDSSGEVCLDILKDER------W 90

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2217329837 4622 NPqTSSFLQVLVSVQSLIlvAEPYfNEPGYERSRGTPSGtQSSREYDGNIRQAT 4675
Cdd:pfam00179   91 SP-ALTLEQVLLSIQSLL--SEPN-PEDPLNAEAAKLYR-KNREEFEKKVREYV 139

Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217329837  287 ANRRETFTSWPHvgYRWAQPDPMAQAGFYHQPAssgDDRAMCFTCSVCLVCWEPTDEPWSEHERHSPNCPFVKG 360
Cdd:cd00022      1 EARLKTFKNWPI--SLKVTPEKLAEAGFYYTGR---GDEVKCFFCGLELKNWEPGDDPWEEHKRWSPNCPFVLL 69

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        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837  4539 VRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTgghsvRFNPNLYNDGKVCLSILNTwhgrpe 4618
Cdd:smart00212   20 YPVDDENLLEWTGTIVGPPGTPYEGGVFKLTIEFPEDYPFKPPKVKFITK-----IYHPNVDSSGEICLDILKQ------ 88

                            90       100       110
                    ....*....|....*....|....*....|.
gi 2217329837  4619 EKWNPqTSSFLQVLVSVQSliLVAEPYFNEP 4649
Cdd:smart00212   89 EKWSP-ALTLETVLLSLQS--LLSEPNPDSP 116

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 R1-R2 and related proteins; The E2R subfamily includes mammalian ubiquitin-conjugating enzymes E2 R1 (UBE2R1/UBCH3/CDC34, EC 2.3.2.23 and EC 2.3.2.24), and E2 R2 (UBE2R2/UBC3B/CDC34B, EC 2.3.2.23), which accept ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, UBE2R1 catalyzes 'Lys-48'-linked polyubiquitination. It also involved in the degradation of beta-catenin. In vitro, UBE2R2 catalyzes monoubiquitination and 'Lys-48'-linked polyubiquitination. It may be involved in the degradation of katenin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4542 DEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSILntwHG------ 4615
Cdd:cd23803     24 DEDNLFEWEVAIFGPPNTLYEGGYFKAHMKFPPDYPYSPPSFRFLTKMWH-----PNVYENGDVCISIL---HPpvddpq 95

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2217329837 4616 ---RPEEKWNPqTSSFLQVLVSVQSLilvaepyFNEP 4649
Cdd:cd23803     96 sgeLPSERWNP-TQNVRTILLSVISL-------LNEP 124

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 G2 and related proteins; The subfamily includes mammalian ubiquitin-conjugating enzymes E2 G2 (UBE2G2/UBC7), yeast E2 ubiquitin-conjugating enzyme 7 (UBC7) 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. In vitro, UBE2G2 catalyzes 'Lys-48'-linked polyubiquitination. It is involved in endoplasmic reticulum-associated degradation (ERAD) and is required for sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation. UBC7, also called ubiquitin-conjugating enzyme E2-18 kDa, functions in the degradation of misfolded or regulated proteins localized in the endoplasmic reticulum (ER) lumen or membrane via the ubiquitin-proteasome system.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4542 DEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTgghsvRFNPNLYNDGKVCLSILNTWHGRP---- 4617
Cdd:cd23796     25 SEDNFFEWEALIQGPEGTPFEGGVFPARLTFPKDYPLSPPKMKFTCE-----MFHPNIYPDGRVCISILHAPGDDPmgye 99

                           90       100
                   ....*....|....*....|....*....
gi 2217329837 4618 --EEKWNPqTSSFLQVLVSVQSLIlvAEP 4644
Cdd:cd23796    100 ssSERWSP-VQSVEKILLSVVSML--AEP 125

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4547 DIMK--VLITGPADTPYANGCFEFDVYFPQDYPSSPPlvnlettgghSVRF-----NPNLYNDGKVCLSILntwhgrpEE 4619
Cdd:cd23790     30 NIMVwnAVIFGPEDTPWEGGTFKLRLEFSEEYPNKPP----------KVRFvskmfHPNVYADGSICLDIL-------QN 92

                           90
                   ....*....|....*....
gi 2217329837 4620 KWNPqTSSFLQVLVSVQSL 4638
Cdd:cd23790     93 RWSP-TYDVSAILTSIQSL 110

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4550 KVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSILNtwhgrpeEKWNPQTsSFL 4629
Cdd:cd23833     31 KVLMEGPEGTPYEGGVFLLYVEFPEEYPVKPPEVRFITPIYH-----CNINSDGRICHSILD-------RNYTPDT-TMR 97

                           90
                   ....*....|....*
gi 2217329837 4630 QVLVSVQSLILVAEP 4644
Cdd:cd23833     98 EILDAVYGLLLTPEP 112

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4553 ITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSILNtwhgrpeEKWNPQ-TSSflQV 4631
Cdd:cd23792     35 IMGPPDSPYQGGVFFLNIHFPTDYPFKPPKVAFTTKIYH-----PNINSNGSICLDILK-------DQWSPAlTIS--KV 100

                           90
                   ....*....|...
gi 2217329837 4632 LVSVQSLILVAEP 4644
Cdd:cd23792    101 LLSICSLLTDPNP 113

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 2217329837 4539 VRC--DEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSILNTwhgR 4616
Cdd:cd23805     18 ISCwpKDDSLDELEAQIQGPEGTPYEGGVFKLEITIPERYPFEPPKVRFLTPIYH-----PNIDSAGRICLDILKM---P 89

                           90       100
                   ....*....|....*....|....*...
gi 2217329837 4617 PEEKWNPqTSSFLQVLVSVQSLIlvAEP 4644
Cdd:cd23805     90 PKGSWKP-SLNISTVLTSIRLLL--AEP 114

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin conjugating enzyme E2 E1-E3 and related proteins; The E2E subfamily includes mammalian ubiquitin-conjugating enzyme E2 E1-3 (UBE2E1/UBCH6, UBE2E2/UBCH8, UBE2E3/UBCH9) and similar proteins. UBE2E, also known as (E3-independent) E2 ubiquitin-conjugating enzyme E, or E2 ubiquitin-conjugating enzyme E, accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. UBE2E1 (EC 2.3.2.23 and EC 2.3.2.24) catalyzes the covalent attachment of ISG15 to other proteins. It mediates the selective degradation of short-lived and abnormal proteins. In vitro, it also catalyzes 'Lys-48'-linked polyubiquitination. In vitro, both UBE2E2 (EC 2.3.2.23) and UBE2E3 (EC 2.3.2.23) catalyze 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. UBE2E2 catalyzes the ISGylation of influenza A virus NS1 protein. UBE2E3 participates in the regulation of trans-epithelial sodium transport in renal cells. It may be involved in cell growth arrest.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4553 ITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHSvrfnpNLYNDGKVCLSILntwhgrpEEKWNPQ-TSSflQV 4631
Cdd:cd23793     34 ILGPPGSVYEGGVFFLDIHFPPDYPFKPPKVTFRTRIYHC-----NINSQGVICLDIL-------KDNWSPAlTIS--KV 99

                           90
                   ....*....|....
gi 2217329837 4632 LVSVQSLILVAEPY 4645
Cdd:cd23793    100 LLSICSLLTDCNPA 113

ubiquitin-conjugating enzyme; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4542 DEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSILntwhgrpEEKW 4621
Cdd:PTZ00390    27 DPGNYRHFKILMEGPDGTPYEGGYYKLELFLPEQYPMEPPKVRFLTKIYH-----PNIDKLGRICLDIL-------KDKW 94

                           90       100
                   ....*....|....*....|....*.
gi 2217329837 4622 NPQtssfLQ---VLVSVQSLILVAEP 4644
Cdd:PTZ00390    95 SPA----LQirtVLLSIQALLSAPEP 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 2217329837 4547 DIMK--VLITGPADtPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSIL---NTWHGRPEEKW 4621
Cdd:cd23955     26 DLFEwhVNIRGPDG-PYSGVILHLELTFPEDYPNSPPSVRLLTPLPH-----PNVFTGNYICLDMLenfAKHHSKPYSGW 99

                           90
                   ....*....|....*....
gi 2217329837 4622 NPQTsSFLQVLVSVQSLIL 4640
Cdd:cd23955    100 SPAY-TVQSILLQLQAFLF 117

Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain of ubiquitin-conjugating enzyme E2 K and related proteins; The E2J subfamily includes mammalian ubiquitin-conjugating enzymes E2 K (UBE2K/HIP2/LIG), yeast ubiquitin-conjugating enzyme E2 1 (UBC1), and plant ubiquitin-conjugating enzyme E2 27 (UBC27). 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. UBE2K is also called huntingtin-interacting protein 2 (HIP-2), ubiquitin-conjugating enzyme E2-25 kDa, or ubiquitin-conjugating enzyme E2(25K). In vitro, in the presence or absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, UBE2K catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. It does not transfer ubiquitin directly, but elongates monoubiquitinated substrate proteins. Saccharomyces cerevisiae UBC1, also called ubiquitin-conjugating enzyme E2-24 kDa, functions in the 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 HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4537 VFVRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYND-GKVCLSILNTwhg 4615
Cdd:cd23800     21 IKVELVGDDLTHLKGEIAGPPDTPYEGGTFVLDIKIPDTYPFEPPKMKFITKIWH-----PNISSQtGAICLDILKD--- 92

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2217329837 4616 rpeeKWNP----QTssflqVLVSVQSLILVAEP 4644
Cdd:cd23800     93 ----QWSPaltlRT-----ALLSIQALLSAPEP 116

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4552 LITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGhsvRFNPNLyndgKVCLSILNtWHgrPEEkWNPqTSSFLQV 4631
Cdd:cd23799     33 TIRGPPDTPYEGGIYHGKIVFPPDYPFKPPSIYMLTPNG---RFETNT----KICLSISS-FH--PES-WNP-AWSIRTI 100

                   ....*..
gi 2217329837 4632 LVSVQSL 4638
Cdd:cd23799    101 LIGLLSF 107

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4539 VRCDEERLDIMKVLITgPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHsvrfnPNLYNDGKVCLSILNTwhgrpe 4618
Cdd:cd23801     23 LSVDESNVLKWTGLLV-PDNPPYNKGAFRIEITFPAEYPFKPPKITFKTKIYH-----PNVDEKGQVCLPIISP------ 90

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2217329837 4619 EKWNPQTSSfLQVLvsvQSLI-LVAEPYFNEPG 4650
Cdd:cd23801     91 ENWKPATKI-DQVL---QALLaLINDPEPEHPL 119

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4560 PYANGCFEFDVYFPQDYPSSPPlvnlettgghSVRFNPNLY------NDGKVCLSilntwhgRPEEKWNPQTSSFLQVLV 4633
Cdd:cd23814     40 LYKGGIFRFTISIPDNYPDGPP----------RVTFLSPVFhplvdpQTGELDLS-------RAFPKWRPGKHHIWHVLN 102

                   ....
gi 2217329837 4634 SVQS 4637
Cdd:cd23814    103 YLKR 106

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217329837 4549 MKVLITGPADTPYANGCFEFDVYFPQDYPSSPPlvnlettgghSVRF-----NPNLynD---GKVCLSILN-TW 4613
Cdd:cd23797     27 FIVKFHGPKDTPYEGGVWKVRVELPDDYPYKSP----------SIGFvnkifHPNI--DeasGSVCLDVINqTW 88

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217329837 4551 VLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLettggHSVRFNPNLY-NDGKVCLSILNTwhgrpEEKWNPqTSSFL 4629
Cdd:cd23806     33 AKIKGLKDTIWEGGIFRLTLKFSENYNYVPPEVQF-----HTIPFHPNVDpITGRPCIDFLDD-----PEKWNP-SYSLK 101

                           90       100
                   ....*....|....*....|
gi 2217329837 4630 QVLVSVQSLIlvAEPYFNEP 4649
Cdd:cd23806    102 SILLSIQVLL--SNPVLENP 119

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217329837 4558 DTPYANGCFEFDVYFPQDYPSSPPLVNLettggHSVRFNPNLY-NDGKVCLSILNTW 4613
Cdd:COG5078     52 GGPTYGDTHRIEITLPESYPQAPPQVRW-----LTPIFHPNIYeAGGSVCIGRADHW 103