UBR-box found in UBR4, UBR5, UBR6/FBOX11, UBR7 and similar proteins; This family includes UBR4 (EC 2.3.2.27), UBR5 (EC 2.3.2.26), UBR6/FBOX11 and UBR7 (EC 2.3.2.27). Both UBR4 (also called 600 kDa retinoblastoma protein-associated factor, or N-recognin-4, or retinoblastoma-associated factor of 600 kDa, or RBAF600, or p600, or zinc finger UBR1-type protein 1) and UBR7 (also called N-recognin-7) are RING-type E3 ubiquitin ligases of the Arg/N-end rule degradation pathway. They recognize and bind to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR5 (also called E3 ubiquitin-protein ligase, HECT domain-containing 1, E3 ligase identified by differential display (EDD), hyperplastic discs protein homolog (HYD), progestin-induced protein, or N-recognin-5) is a HECT (homologous to E6-AP C-terminus)-type E3 ubiquitin-protein ligase that acts as a key regulator of the ubiquitin proteasome system in both cancer and developmental biology. It is required for Wnt signal responses in Drosophila and human cell lines downstream of activated Armadillo/beta-catenin. It also plays a key role in ciliogenesis by regulating centriolar satellite stability and primary cilia. UBR6 (also called FBOX11, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1)), is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumor initiation and progression. UBR6 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. UBR6 does not bind N-terminal signals.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2000364024  767 CSFVDTHERFVEQDWFHCKTCGLRGSNGCCAICAIVCHHGHDVRYHGRSKFYCDCG--CSSKCK 828
Cdd:cd19671      1 CTFEKTGRKYIKQPWYHCYTCGLIDGLGVCEACARKCHKGHDLVYIGYSNFYCDCGssGPGKCK 64

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 2000364024 1545 RLNRELRSLRNLLPvhlgSTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMttgggTVRFN 1624
Cdd:pfam00179    1 RLQKELKELLKDPP----PGISAGPVDDNLFEWKVTIIGPDGTPYEGGVFKLSVEFPEDYPFKPPKVKFT-----TKIYH 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2000364024 1625 PNLYVNGKVCLSLLGTWRggatgnetWTKKSSLLQVLVSIQS 1666
Cdd:pfam00179   72 PNVDSSGEVCLDILKDER--------WSPALTLEQVLLSIQS 105

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 2000364024  1545 RLNRELRSLRNLLPVHlgsTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:smart00212    1 RLLKELKELRKDPPPG---FTAYPVDDENLLEWTGTIVGPPGTPYEGGVFKLTIEFPEDYPFKPPKVKFITK-----IYH 72

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 2000364024  1625 PNLYVNGKVCLSLLGTwrggatgnETWTKKSSLLQVLVSIQS 1666
Cdd:smart00212   73 PNVDSSGEICLDILKQ--------EKWSPALTLETVLLSLQS 106

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024  454 IGISTKNDDLKLGSTRST--------VWGIRRDGRKWHNSKKISYCPRYcspIEPASSVTVRLDLEQGELGFYINDIWQG 525
Cdd:cd12876     63 VGVGTKKADLHAYRYEFCsllgedeeSWGLSYKGLLWHDGQSRPYTSPF---GNQGTIIGVHLDMWRGTLTFYKNGKPLG 139

                           90
                   ....*....|....*..
gi 2000364024  526 VAYAGLPLDPSYYAFVS 542
Cdd:cd12876    140 VAFTGLNGVKPLYPMVS 156

Putative zinc finger in N-recognin (UBR box); This region is found in E3 ubiquitin ligases that recognize N-recognins.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2000364024  781 WFHCKTCGLRGSNGCCAICAIVC-HHGHDVR-YHGRSKFYCDCG 822
Cdd:pfam02207   11 VYRCLTCSLDPTCVICYSCFINCdHEGHDYElFTSRGGGCCDCG 54

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024  449 DASFSIGISTKNDDLK---LGSTRSTVWGIR-RDGRKWHNSKKisycPRYCSPI-EPASSVTVRLDLEQGELGFYINDIW 523
Cdd:pfam00622   13 GGGWRVGWATKSVPRKgerFLGDESGSWGYDgWTGKKYWASTS----PLTGLPLfEPGDVIGCFLDYEAGTISFTKNGKS 88

                           90       100
                   ....*....|....*....|
gi 2000364024  524 QGVAYAGLPLDPSYYAFVSL 543
Cdd:pfam00622   89 LGYAFRDVPFAGPLFPAVSL 108

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 2000364024 1545 RLNRELRSLRNLLPvhlgSTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTGGGtvRFN 1624
Cdd:cd23837      6 RVRKEWKLLKTSLP----DGIFVRAYEDRMDLLRALIVGPEGTPYEDGLFFFDIQLPPDYPNVPPKVHYHSWTGG--RLN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024 1625 PNLYVNGKVCLSLLGTWRGGatGNETWT-KKSSLLQVLVSIQSAILGSEyPYFNEPGVESRWGTAQGDLQKRVsenggY- 1702
Cdd:cd23837     80 PNLYEDGKVCLSLLGTWSGK--GTEKWTpKSSNLLQVLVSIQGLVLVKE-PYYNEAGYDKQRGTQEGRENSRM-----Yn 151

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 2000364024 1703 ERLRVATLRYaIIEQIRYPPANFADLIRTHFRLKQDHILAVADSWIE 1749
Cdd:cd23837    152 EMAFLLSLQS-MLHLLRNPPEGFEDEIRSHFRKRGPRLLARLEAWLE 197

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 2000364024 1545 RLNRELRSLRNLLPvhlgSTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMttgggTVRFN 1624
Cdd:pfam00179    1 RLQKELKELLKDPP----PGISAGPVDDNLFEWKVTIIGPDGTPYEGGVFKLSVEFPEDYPFKPPKVKFT-----TKIYH 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2000364024 1625 PNLYVNGKVCLSLLGTWRggatgnetWTKKSSLLQVLVSIQS 1666
Cdd:pfam00179   72 PNVDSSGEVCLDILKDER--------WSPALTLEQVLLSIQS 105

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 2000364024 1545 RLNRELRSLRNLLPVHlgstIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMttgggTVRFN 1624
Cdd:cd00195      2 RLQKELKELQKNPPPG----ISVEPVDDDLFHWKATIKGPEGTPYEGGVFKLDIEFPDDYPFKPPKVRFL-----TPIYH 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2000364024 1625 PNLYVNGKVCLSLLGTwrggatgnETWTKKSSLLQVLVSIQSAI 1668
Cdd:cd00195     73 PNVDPDGEICLDILKS--------EGWSPALTLRSVLLSIQSLL 108

UBR-box found in RING-type E3 ubiquitin-protein ligase UBR4 and similar proteins; UBR4 (EC 2.3.2.27; also called 600 kDa retinoblastoma protein-associated factor, N-recognin-4, retinoblastoma-associated factor of 600 kDa, RBAF600, p600, or zinc finger UBR1-type protein 1) is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR4 acts as a multifunctional protein with roles in anoikis, viral transformation, and protein degradation, as well as in neurogenesis, neuronal migration, neuronal signaling, and survival. The family also includes Arabidopsis thaliana auxin transport protein BIG (also called protein attenuated shade avoidance 1, protein corymbosa1, protein dark over-expression of cab 1, protein low phosphate-resistant root 1, protein transport inhibitor response 3, or protein umbrella 1). It is a calossin-like protein required for auxin efflux and polar auxin transport (PAT) influencing auxin-mediated developmental responses in Arabidopsis.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2000364024  767 CSFVDTHERFVEQDWFHCKTCGLRGSNGCCAICAIVCHHGHDVRYHGRSKFYCDCG---CSSKCK 828
Cdd:cd19674      3 CTFASTGKNYARQHWYECYTCFLNGNEGVCEVCARVCHKGHDLVYSKTSSFFCDCGaggGPSKCK 67

UBR-box found in UBR family of E3 ubiquitin ligases (UBR1-7) and similar proteins; The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases (UBR1-7, also called N-recognins) that directly binds N-terminal degradation signals (N-degrons) in substrate proteins to facilitate substrate ubiquitination and proteasomal degradation via the ubiquitin-proteasome system (UPS). UBR1 and UBR2 bind all type-1 and type-2 N-degrons. They mediate ubiquitination and proteolysis of short-lived regulators and misfolded proteins. UBR4 binds both type-1 and type-2 N-degrons and is involved in proteome-wide turnover of cell surface proteins. UBR5 preferentially binds type-1 N-degrons and mediates ubiquitination of short-lived proteins. UBR3, UBR6 (also called FBXO11), and UBR7 may not bind efficiently to N-degrons. UBR3 is a RING-type E3 ubiquitin ligase with a function in olfactory and other sensory systems. UBR6 is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumor initiation and progression. It does not bind N-terminal signals. UBR7 is a RING-type E3 ubiquitin ligase that may play an important role in spermiogenesis and fertilization.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2000364024  767 CSFVDTHerfVEQDWFHCKTCGLRGSNGCCAICAIVCHHGHDVRYHGRSKFYCDCG----CSSKCK 828
Cdd:cd19669      1 CTFSITG---INQVMYHCLTCSLDDNSGICEECAKKCHEGHDVVYIGSGSGFCDCGdssaKSGFCK 63

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 2000364024 1545 RLNRELRSLRNLLPVHlgstIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:cd23790      6 RLMRDFKRLQKDPPEG----ISAAPVEDNIMVWNAVIFGPEDTPWEGGTFKLRLEFSEEYPNKPPKVRFVSK-----MFH 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2000364024 1625 PNLYVNGKVCLSLLgtwrggatgNETWTKKSSLLQVLVSIQS 1666
Cdd:cd23790     77 PNVYADGSICLDIL---------QNRWSPTYDVSAILTSIQS 109

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 2000364024 1545 RLNRELRSLRNLLPvhlgSTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:cd23805      2 RLKRELQLLQKDPP----PGISCWPKDDSLDELEAQIQGPEGTPYEGGVFKLEITIPERYPFEPPKVRFLTP-----IYH 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2000364024 1625 PNLYVNGKVCLSLLGTWRGGAtgnetWTKKSSLLQVLVSIQS 1666
Cdd:cd23805     73 PNIDSAGRICLDILKMPPKGS-----WKPSLNISTVLTSIRL 109

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 2000364024 1545 RLNRELRSLRNLLP---VHLGStiavrVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtv 1621
Cdd:cd23812      2 RLLKELRELQKEPNdpdIVLGP-----VEDDDLFRWEAVIKGPKDTPYEGGRFELAIQVPSNYPISPPKVKFVTK----- 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2000364024 1622 RFNPNL-YVNGKVCLSLLGTwrggatgneTWTKKSSLLQVLVSIQS 1666
Cdd:cd23812     72 IFHPNVhFKTGEICLDILKT---------AWSPAWTLQSVCRAILA 108

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 2000364024 1545 RLNRELRSLRNLLPvhlGSTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:cd23796      3 RLMAEYKQLTLNPP---EGIVAGPVSEDNFFEWEALIQGPEGTPFEGGVFPARLTFPKDYPLSPPKMKFTCE-----MFH 74

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2000364024 1625 PNLYVNGKVCLSLLGT----WRGGATGNETWTKKSSLLQVLVSIQSAIlgseypyfNEPGVES 1683
Cdd:cd23796     75 PNIYPDGRVCISILHApgddPMGYESSSERWSPVQSVEKILLSVVSML--------AEPNDES 129

Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway; Domain is involved in recognition of N-end rule substrates in yeast Ubr1p

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024   767 CSFVDTHERFVeqdwFHCKTCGLRGSNGCCAICAI-VCHHGHDVRYH-GRSKFYCDCGCSS------KCK 828
Cdd:smart00396    3 CGYKFTGGEVI----YRCKTCGLDPTCVLCSDCFRpSCHKGHDVSLKtSRGSGICDCGDKEawnedlKCK 68

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 2000364024 1545 RLNRELRSLRNLLPVHlgstIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTGGgtvRFN 1624
Cdd:cd23799      2 RLLKELRELQKDPPPY----IVAAPLEDNILEWHFTIRGPPDTPYEGGIYHGKIVFPPDYPFKPPSIYMLTPNG---RFE 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2000364024 1625 PNLyvngKVCLSLLG----TWrggatgNETWtkksSLLQVLVSIQS 1666
Cdd:cd23799     75 TNT----KICLSISSfhpeSW------NPAW----SIRTILIGLLS 106

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 2000364024 1545 RLNRELRSLRNllPVHLGSTIAVRVDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:cd23800      3 RIKKELKEVQK--DSEAESGIKVELVGDDLTHLKGEIAGPPDTPYEGGTFVLDIKIPDTYPFEPPKMKFITK-----IWH 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2000364024 1625 PNL-YVNGKVCLSLLGTwrggatgneTWTKKSSLLQVLVSIQsAILGS 1671
Cdd:cd23800     76 PNIsSQTGAICLDILKD---------QWSPALTLRTALLSIQ-ALLSA 113

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024  454 IGISTKNDDLKLGSTRST--------VWGIRRDGRKWHNSKKISYCPRYcspIEPASSVTVRLDLEQGELGFYINDIWQG 525
Cdd:cd12876     63 VGVGTKKADLHAYRYEFCsllgedeeSWGLSYKGLLWHDGQSRPYTSPF---GNQGTIIGVHLDMWRGTLTFYKNGKPLG 139

                           90
                   ....*....|....*..
gi 2000364024  526 VAYAGLPLDPSYYAFVS 542
Cdd:cd12876    140 VAFTGLNGVKPLYPMVS 156

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024 1569 VDERRPFIMQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFNPNLYVNGKVCLSLL 1638
Cdd:cd23795     26 VDDSNIYEWEVMIIGPPDTLYEGGFFKAELTFPDDYPNSPPKMKFITE-----MWHPNVYPDGDVCISIL 90

UBR-box found in F-box only protein 11 (FBXO11) and similar proteins; FBXO11 (also called UBR6, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1)) is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumor initiation and progression. FBXO11 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. FBXO11 does not bind N-terminal signals.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2000364024  767 CSF-VDTHERFVEQDWFHCKTCGLRGSNGCCAICAIVCHHGHDVRYHGRSKFYCDCG 822
Cdd:cd19676      1 CLYkISSYTSFPMHDFYRCLTCNTTDRNAICVNCIKKCHEGHDVEFIRHDRFFCDCG 57

ubiquitin-conjugating enzyme; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024 1545 RLNRELRSLRNLLPVhlGSTIAVRVDERRPFimQAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:PTZ00390     6 RIEKETQNLANDPPP--GIKAEPDPGNYRHF--KILMEGPDGTPYEGGYYKLELFLPEQYPMEPPKVRFLTK-----IYH 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2000364024 1625 PNLYVNGKVCLSLLgtwrggatgNETWTKKSSLLQVLVSIQsAILGSEYP 1674
Cdd:PTZ00390    77 PNIDKLGRICLDIL---------KDKWSPALQIRTVLLSIQ-ALLSAPEP 116

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        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024 1578 QAVIFGPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLmttggGTVRFNPNLYVNGKVCLSLLGTwrggatgNETWTKKSSL 1657
Cdd:cd23798     39 ECGIPGKKGTPWEGGLYKLTMEFPEDYPSKPPKCKF-----DPPLFHPNVYPSGTVCLSILNE-------DKDWKPSITI 106

                   ....*...
gi 2000364024 1658 LQVLVSIQ 1665
Cdd:cd23798    107 KQILLGIQ 114

SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024  436 HVFEWKYKLNLDVDASFSIGISTK----NDDLKLGSTRSTvWGIRRD-GRKWHNSKKisycPRYCSPIEPASSVTVRLDL 510
Cdd:cd11709      1 GKWYWEVRVDSGNGGLIQVGWATKsfslDGEGGVGDDEES-WGYDGSrLRKGHGGSS----GPGGRPWKSGDVVGCLLDL 75

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2000364024  511 EQGELGFYINDIWQGVAYAGLPLDPS-YYAFVSLF 544
Cdd:cd11709     76 DEGTLSFSLNGKDLGVAFTNLFLKGGgLYPAVSLG 110

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 2000364024 1545 RLNRELRSLRNLLPVHLGStiaVRVDERRPFIMQAVIFgPEGTPYDSGCFVFDIYMPPEYPNCPPNIRLMTTgggtvRFN 1624
Cdd:cd23801      4 RLQKELEELRKSGPKYFRD---LSVDESNVLKWTGLLV-PDNPPYNKGAFRIEITFPAEYPFKPPKITFKTK-----IYH 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2000364024 1625 PNLYVNGKVCLSLLGTwrggatgnETW---TKKSSLLQVLV 1662
Cdd:cd23801     75 PNVDEKGQVCLPIISP--------ENWkpaTKIDQVLQALL 107

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000364024 1545 RLNRELRSLRNLLPVHLgsTIAVRVDERRPFIMQavIFGPEGTPYDSGCFVFDIYMPPEYPNCPPnirlmttgggTVRF- 1623
Cdd:cd23808      3 RLQKELKELQKNPPPGI--TLDVADNNLTEWIVT--IEGAPGTLYEGEKFRLRFKFPPDYPIESP----------EVVFv 68

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2000364024 1624 ------NPNLYVNGKVCLSLLGtwrggatgnETWTKKSSLLQVLVSIQS 1666
Cdd:cd23808     69 gppipvHPHVYSNGHICLSILY---------DDWSPALTVSSVCLSILS 108