UBR5_HUMAN
ID UBR5_HUMAN Reviewed; 2799 AA.
AC O95071; B2RP24; J3KMW7; O94970; Q9NPL3;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=E3 ubiquitin-protein ligase UBR5;
DE EC=2.3.2.26;
DE AltName: Full=E3 ubiquitin-protein ligase, HECT domain-containing 1;
DE AltName: Full=HECT-type E3 ubiquitin transferase UBR5;
DE AltName: Full=Hyperplastic discs protein homolog;
DE Short=hHYD;
DE AltName: Full=Progestin-induced protein;
GN Name=UBR5; Synonyms=EDD, EDD1, HYD, KIAA0896;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart, and Placenta;
RX PubMed=10030672; DOI=10.1038/sj.onc.1202249;
RA Callaghan M.J., Russell A.J., Woollatt E., Sutherland G.R.,
RA Sutherland R.L., Watts C.K.W.;
RT "Identification of a human HECT family protein with homology to the
RT Drosophila tumor suppressor gene hyperplastic discs.";
RL Oncogene 17:3479-3491(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH TOPBP1.
RC TISSUE=Fetal brain;
RX PubMed=11714696; DOI=10.1074/jbc.m104347200;
RA Honda Y., Tojo M., Matsuzaki K., Anan T., Matsumoto M., Ando M., Saya H.,
RA Nakao M.;
RT "Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-
RT binding protein for DNA damage response.";
RL J. Biol. Chem. 277:3599-3605(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R., Ishikawa K., Suyama M.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1746, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1969, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1308; SER-1549; THR-1969 AND
RP SER-2486, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP INTERACTION WITH EDVP COMPLEX.
RX PubMed=19287380; DOI=10.1038/ncb1848;
RA Maddika S., Chen J.;
RT "Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3
RT ligase.";
RL Nat. Cell Biol. 11:409-419(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2486, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1549 AND THR-1969, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION AS CDK9 UBIQUITIN LIGASE, AND INTERACTION WITH CDK9 AND
RP TFIIS/TCEA1.
RX PubMed=21127351; DOI=10.1074/jbc.m110.176628;
RA Cojocaru M., Bouchard A., Cloutier P., Cooper J.J., Varzavand K.,
RA Price D.H., Coulombe B.;
RT "Transcription factor IIS cooperates with the E3 ligase UBR5 to
RT ubiquitinate the CDK9 subunit of the positive transcription elongation
RT factor B.";
RL J. Biol. Chem. 286:5012-5022(2011).
RN [19]
RP PHOSPHORYLATION AT SER-110; SER-327; SER-352; SER-578; SER-612; THR-637;
RP SER-808; SER-928; SER-1018; THR-1115; THR-1135; SER-1227; SER-1308;
RP SER-1355; SER-1375; SER-1481; THR-1736; SER-1741; SER-1780; THR-1969;
RP SER-2026; SER-2028; THR-2030; SER-2076; THR-2213; SER-2289 AND SER-2484.
RX PubMed=21924388; DOI=10.1016/j.jprot.2011.08.023;
RA Bethard J.R., Zheng H., Roberts L., Eblen S.T.;
RT "Identification of phosphorylation sites on the E3 ubiquitin ligase
RT UBR5/EDD.";
RL J. Proteomics 75:603-609(2011).
RN [20]
RP FUNCTION IN UBIQUITINATION OF PCK1.
RX PubMed=21726808; DOI=10.1016/j.molcel.2011.04.028;
RA Jiang W., Wang S., Xiao M., Lin Y., Zhou L., Lei Q., Xiong Y., Guan K.L.,
RA Zhao S.;
RT "Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via
RT recruiting the UBR5 ubiquitin ligase.";
RL Mol. Cell 43:33-44(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-327; SER-1549 AND SER-2486,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP FUNCTION.
RX PubMed=22884692; DOI=10.1016/j.cell.2012.06.039;
RA Gudjonsson T., Altmeyer M., Savic V., Toledo L., Dinant C., Grofte M.,
RA Bartkova J., Poulsen M., Oka Y., Bekker-Jensen S., Mailand N., Neumann B.,
RA Heriche J.K., Shearer R., Saunders D., Bartek J., Lukas J., Lukas C.;
RT "TRIP12 and UBR5 Suppress Spreading of Chromatin Ubiquitylation at Damaged
RT Chromosomes.";
RL Cell 150:697-709(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110; SER-327; SER-578;
RP SER-612; SER-808; SER-1308; SER-1549; THR-1969; SER-2241; SER-2469 AND
RP SER-2486, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP INTERACTION WITH PIH1D1.
RX PubMed=24656813; DOI=10.1016/j.celrep.2014.03.013;
RA Horejsi Z., Stach L., Flower T.G., Joshi D., Flynn H., Skehel J.M.,
RA O'Reilly N.J., Ogrodowicz R.W., Smerdon S.J., Boulton S.J.;
RT "Phosphorylation-dependent PIH1D1 interactions define substrate specificity
RT of the R2TP cochaperone complex.";
RL Cell Rep. 7:19-26(2014).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1549 AND SER-1990, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP INTERACTION WITH HUMAN T-CELL LEUKEMIA VIRUS 1 PROTEIN HBZ.
RX PubMed=29441057; DOI=10.3389/fmicb.2018.00080;
RA Panfil A.R., Al-Saleem J., Howard C.M., Shkriabai N., Kvaratskhelia M.,
RA Green P.L.;
RT "Stability of the HTLV-1 Antisense-Derived Protein, HBZ, Is Regulated by
RT the E3 Ubiquitin-Protein Ligase, UBR5.";
RL Front. Microbiol. 9:80-80(2018).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.04 ANGSTROMS) OF 2391-2455, AND MUTAGENESIS OF
RP CYS-2768.
RX PubMed=11287654; DOI=10.1073/pnas.071552198;
RA Deo R.C., Sonenberg N., Burley S.K.;
RT "X-ray structure of the human hyperplastic discs protein: an ortholog of
RT the C-terminal domain of poly(A)-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4414-4419(2001).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which is a component of the N-end
CC rule pathway. Recognizes and binds to proteins bearing specific N-
CC terminal residues that are destabilizing according to the N-end rule,
CC leading to their ubiquitination and subsequent degradation (By
CC similarity). Involved in maturation and/or transcriptional regulation
CC of mRNA by activating CDK9 by polyubiquitination. May play a role in
CC control of cell cycle progression. May have tumor suppressor function.
CC Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA
CC damage response. Plays an essential role in extraembryonic development.
CC Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage
CC response by acting as a suppressor of RNF168, an E3 ubiquitin-protein
CC ligase that promotes accumulation of 'Lys-63'-linked histone H2A and
CC H2AX at DNA damage sites, thereby acting as a guard against excessive
CC spreading of ubiquitinated chromatin at damaged chromosomes.
CC {ECO:0000250, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808,
CC ECO:0000269|PubMed:22884692}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds TOPBP1. Associates with CDK9 and TFIIS/TCEA1 and forms a
CC transcription regulatory complex made of CDK9, RNAP II, UBR5 and
CC TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma
CC fibrinogen/FGG) by recruiting their promoters. Associates with the E3
CC ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins
CC (EDVP complex). Interacts directly with DYRK2. Interacts with PIH1D1
CC (PubMed:24656813). {ECO:0000269|PubMed:11714696,
CC ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:21127351,
CC ECO:0000269|PubMed:24656813}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human T-cell leukemia
CC virus 1/HTLV-1 protein HBZ; this interaction modulates HBZ stability.
CC {ECO:0000269|PubMed:29441057}.
CC -!- INTERACTION:
CC O95071; P35222: CTNNB1; NbExp=6; IntAct=EBI-358329, EBI-491549;
CC O95071; P49841: GSK3B; NbExp=8; IntAct=EBI-358329, EBI-373586;
CC O95071; Q9BPZ3: PAIP2; NbExp=5; IntAct=EBI-358329, EBI-2957445;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95071-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95071-2; Sequence=VSP_054399;
CC -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in testis and
CC expressed at high levels in brain, pituitary and kidney.
CC -!- MISCELLANEOUS: A cysteine residue is required for ubiquitin-thioester
CC formation.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74919.3; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF006010; AAD01259.2; -; mRNA.
DR EMBL; U95000; AAF88143.1; -; mRNA.
DR EMBL; AB020703; BAA74919.3; ALT_INIT; mRNA.
DR EMBL; AP002907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002981; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137234; AAI37235.1; -; mRNA.
DR CCDS; CCDS34933.1; -. [O95071-1]
DR CCDS; CCDS64946.1; -. [O95071-2]
DR RefSeq; NP_001269802.1; NM_001282873.1. [O95071-2]
DR RefSeq; NP_056986.2; NM_015902.5. [O95071-1]
DR PDB; 1I2T; X-ray; 1.04 A; A=2393-2453.
DR PDB; 2QHO; X-ray; 1.85 A; B/D/F/H=180-230.
DR PDB; 3PT3; X-ray; 1.97 A; A/B=2687-2799.
DR PDBsum; 1I2T; -.
DR PDBsum; 2QHO; -.
DR PDBsum; 3PT3; -.
DR SMR; O95071; -.
DR BioGRID; 119501; 476.
DR CORUM; O95071; -.
DR DIP; DIP-32930N; -.
DR ELM; O95071; -.
DR IntAct; O95071; 145.
DR MINT; O95071; -.
DR STRING; 9606.ENSP00000429084; -.
DR GlyGen; O95071; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95071; -.
DR PhosphoSitePlus; O95071; -.
DR SwissPalm; O95071; -.
DR BioMuta; UBR5; -.
DR EPD; O95071; -.
DR jPOST; O95071; -.
DR MassIVE; O95071; -.
DR MaxQB; O95071; -.
DR PaxDb; O95071; -.
DR PeptideAtlas; O95071; -.
DR PRIDE; O95071; -.
DR ProteomicsDB; 50641; -. [O95071-1]
DR Antibodypedia; 13236; 298 antibodies from 37 providers.
DR DNASU; 51366; -.
DR Ensembl; ENST00000220959.8; ENSP00000220959.4; ENSG00000104517.13. [O95071-2]
DR Ensembl; ENST00000520539.6; ENSP00000429084.1; ENSG00000104517.13. [O95071-1]
DR GeneID; 51366; -.
DR KEGG; hsa:51366; -.
DR MANE-Select; ENST00000520539.6; ENSP00000429084.1; NM_015902.6; NP_056986.2.
DR UCSC; uc003ykr.3; human. [O95071-1]
DR CTD; 51366; -.
DR DisGeNET; 51366; -.
DR GeneCards; UBR5; -.
DR HGNC; HGNC:16806; UBR5.
DR HPA; ENSG00000104517; Low tissue specificity.
DR MIM; 608413; gene.
DR neXtProt; NX_O95071; -.
DR OpenTargets; ENSG00000104517; -.
DR PharmGKB; PA162408175; -.
DR VEuPathDB; HostDB:ENSG00000104517; -.
DR eggNOG; KOG0943; Eukaryota.
DR GeneTree; ENSGT00940000156357; -.
DR InParanoid; O95071; -.
DR OMA; EAKFRRD; -.
DR OrthoDB; 717at2759; -.
DR PhylomeDB; O95071; -.
DR TreeFam; TF314406; -.
DR PathwayCommons; O95071; -.
DR SignaLink; O95071; -.
DR SIGNOR; O95071; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51366; 287 hits in 1135 CRISPR screens.
DR ChiTaRS; UBR5; human.
DR EvolutionaryTrace; O95071; -.
DR GeneWiki; UBR5; -.
DR GenomeRNAi; 51366; -.
DR Pharos; O95071; Tbio.
DR PRO; PR:O95071; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O95071; protein.
DR Bgee; ENSG00000104517; Expressed in ventricular zone and 203 other tissues.
DR ExpressionAtlas; O95071; baseline and differential.
DR Genevisible; O95071; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:HGNC-UCL.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:2000780; P:negative regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:BHF-UCL.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; IDA:HGNC-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:FlyBase.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:BHF-UCL.
DR GO; GO:2000779; P:regulation of double-strand break repair; IBA:GO_Central.
DR CDD; cd14423; CUE_UBR5; 1.
DR Gene3D; 2.130.10.30; -; 1.
DR IDEAL; IID00191; -.
DR InterPro; IPR024725; E3_UbLigase_EDD_UBA.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR036053; PABP-dom.
DR InterPro; IPR002004; PABP_HYD.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR003126; Znf_UBR.
DR Pfam; PF11547; E3_UbLigase_EDD; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00658; PABP; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00517; PolyA; 1.
DR SMART; SM00396; ZnF_UBR1; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR SUPFAM; SSF63570; SSF63570; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS51309; PABC; 1.
DR PROSITE; PS51157; ZF_UBR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; DNA damage; DNA repair;
KW Host-virus interaction; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..2799
FT /note="E3 ubiquitin-protein ligase UBR5"
FT /id="PRO_0000086931"
FT DOMAIN 2377..2454
FT /note="PABC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00641"
FT DOMAIN 2462..2799
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ZN_FING 1177..1245
FT /note="UBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00508"
FT REGION 77..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..648
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 999..1031
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1052..1075
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1299..1318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1515..1740
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1859..1890
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1984..2021
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2117..2142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2323..2392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2473..2493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..344
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..602
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..632
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1017..1031
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1072
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1521..1551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1563..1577
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1578..1607
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1622..1651
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1660..1685
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1693..1740
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1876..1890
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1996..2014
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2329..2370
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2473..2491
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2768
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 637
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 928
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1018
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1115
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1135
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1227
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1308
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 1355
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1375
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1481
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1736
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1741
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1746
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 1780
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 1969
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1990
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2026
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2028
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2030
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2076
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2213
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2289
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2484
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21924388"
FT MOD_RES 2486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 2474
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485"
FT /id="VSP_054399"
FT VARIANT 2150
FT /note="S -> R (in dbSNP:rs1062822)"
FT /id="VAR_051466"
FT MUTAGEN 2768
FT /note="C->A: Loss of ubiquitin binding."
FT /evidence="ECO:0000269|PubMed:11287654"
FT CONFLICT 134
FT /note="S -> P (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="E -> K (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="S -> Y (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 374..375
FT /note="IG -> M (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 772
FT /note="D -> H (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 780
FT /note="Q -> R (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 884
FT /note="D -> G (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 1811
FT /note="S -> P (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 2144
FT /note="L -> H (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 2282
FT /note="K -> R (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT CONFLICT 2489
FT /note="D -> N (in Ref. 2; AAF88143)"
FT /evidence="ECO:0000305"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:2QHO"
FT HELIX 187..196
FT /evidence="ECO:0007829|PDB:2QHO"
FT HELIX 202..211
FT /evidence="ECO:0007829|PDB:2QHO"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:2QHO"
FT HELIX 216..224
FT /evidence="ECO:0007829|PDB:2QHO"
FT HELIX 2394..2408
FT /evidence="ECO:0007829|PDB:1I2T"
FT HELIX 2410..2412
FT /evidence="ECO:0007829|PDB:1I2T"
FT HELIX 2413..2420
FT /evidence="ECO:0007829|PDB:1I2T"
FT HELIX 2425..2433
FT /evidence="ECO:0007829|PDB:1I2T"
FT HELIX 2435..2452
FT /evidence="ECO:0007829|PDB:1I2T"
FT HELIX 2687..2692
FT /evidence="ECO:0007829|PDB:3PT3"
FT STRAND 2695..2698
FT /evidence="ECO:0007829|PDB:3PT3"
FT HELIX 2704..2720
FT /evidence="ECO:0007829|PDB:3PT3"
FT HELIX 2723..2734
FT /evidence="ECO:0007829|PDB:3PT3"
FT STRAND 2751..2756
FT /evidence="ECO:0007829|PDB:3PT3"
FT STRAND 2764..2766
FT /evidence="ECO:0007829|PDB:3PT3"
FT TURN 2767..2770
FT /evidence="ECO:0007829|PDB:3PT3"
FT STRAND 2771..2775
FT /evidence="ECO:0007829|PDB:3PT3"
FT HELIX 2780..2791
FT /evidence="ECO:0007829|PDB:3PT3"
SQ SEQUENCE 2799 AA; 309352 MW; 871300DB404FF561 CRC64;
MTSIHFVVHP LPGTEDQLND RLREVSEKLN KYNLNSHPPL NVLEQATIKQ CVVGPNHAAF
LLEDGRVCRI GFSVQPDRLE LGKPDNNDGS KLNSNSGAGR TSRPGRTSDS PWFLSGSETL
GRLAGNTLGS RWSSGVGGSG GGSSGRSSAG ARDSRRQTRV IRTGRDRGSG LLGSQPQPVI
PASVIPEELI SQAQVVLQGK SRSVIIRELQ RTNLDVNLAV NNLLSRDDED GDDGDDTASE
SYLPGEDLMS LLDADIHSAH PSVIIDADAM FSEDISYFGY PSFRRSSLSR LGSSRVLLLP
LERDSELLRE RESVLRLRER RWLDGASFDN ERGSTSKEGE PNLDKKNTPV QSPVSLGEDL
QWWPDKDGTK FICIGALYSE LLAVSSKGEL YQWKWSESEP YRNAQNPSLH HPRATFLGLT
NEKIVLLSAN SIRATVATEN NKVATWVDET LSSVASKLEH TAQTYSELQG ERIVSLHCCA
LYTCAQLENS LYWWGVVPFS QRKKMLEKAR AKNKKPKSSA GISSMPNITV GTQVCLRNNP
LYHAGAVAFS ISAGIPKVGV LMESVWNMND SCRFQLRSPE SLKNMEKASK TTEAKPESKQ
EPVKTEMGPP PSPASTCSDA SSIASSASMP YKRRRSTPAP KEEEKVNEEQ WSLREVVFVE
DVKNVPVGKV LKVDGAYVAV KFPGTSSNTN CQNSSGPDAD PSSLLQDCRL LRIDELQVVK
TGGTPKVPDC FQRTPKKLCI PEKTEILAVN VDSKGVHAVL KTGNWVRYCI FDLATGKAEQ
ENNFPTSSIA FLGQNERNVA IFTAGQESPI ILRDGNGTIY PMAKDCMGGI RDPDWLDLPP
ISSLGMGVHS LINLPANSTI KKKAAVIIMA VEKQTLMQHI LRCDYEACRQ YLMNLEQAVV
LEQNLQMLQT FISHRCDGNR NILHACVSVC FPTSNKETKE EEEAERSERN TFAERLSAVE
AIANAISVVS SNGPGNRAGS SSSRSLRLRE MMRRSLRAAG LGRHEAGASS SDHQDPVSPP
IAPPSWVPDP PAMDPDGDID FILAPAVGSL TTAATGTGQG PSTSTIPGPS TEPSVVESKD
RKANAHFILK LLCDSVVLQP YLRELLSAKD ARGMTPFMSA VSGRAYPAAI TILETAQKIA
KAEISSSEKE EDVFMGMVCP SGTNPDDSPL YVLCCNDTCS FTWTGAEHIN QDIFECRTCG
LLESLCCCTE CARVCHKGHD CKLKRTSPTA YCDCWEKCKC KTLIAGQKSA RLDLLYRLLT
ATNLVTLPNS RGEHLLLFLV QTVARQTVEH CQYRPPRIRE DRNRKTASPE DSDMPDHDLE
PPRFAQLALE RVLQDWNALK SMIMFGSQEN KDPLSASSRI GHLLPEEQVY LNQQSGTIRL
DCFTHCLIVK CTADILLLDT LLGTLVKELQ NKYTPGRREE AIAVTMRFLR SVARVFVILS
VEMASSKKKN NFIPQPIGKC KRVFQALLPY AVEELCNVAE SLIVPVRMGI ARPTAPFTLA
STSIDAMQGS EELFSVEPLP PRPSSDQSSS SSQSQSSYII RNPQQRRISQ SQPVRGRDEE
QDDIVSADVE EVEVVEGVAG EEDHHDEQEE HGEENAEAEG QHDEHDEDGS DMELDLLAAA
ETESDSESNH SNQDNASGRR SVVTAATAGS EAGASSVPAF FSEDDSQSND SSDSDSSSSQ
SDDIEQETFM LDEPLERTTN SSHANGAAQA PRSMQWAVRN TQHQRAASTA PSSTSTPAAS
SAGLIYIDPS NLRRSGTIST SAAAAAAALE ASNASSYLTS ASSLARAYSI VIRQISDLMG
LIPKYNHLVY SQIPAAVKLT YQDAVNLQNY VEEKLIPTWN WMVSIMDSTE AQLRYGSALA
SAGDPGHPNH PLHASQNSAR RERMTAREEA SLRTLEGRRR ATLLSARQGM MSARGDFLNY
ALSLMRSHND EHSDVLPVLD VCSLKHVAYV FQALIYWIKA MNQQTTLDTP QLERKRTREL
LELGIDNEDS EHENDDDTNQ SATLNDKDDD SLPAETGQNH PFFRRSDSMT FLGCIPPNPF
EVPLAEAIPL ADQPHLLQPN ARKEDLFGRP SQGLYSSSAS SGKCLMEVTV DRNCLEVLPT
KMSYAANLKN VMNMQNRQKK EGEEQPVLPE ETESSKPGPS AHDLAAQLKS SLLAEIGLTE
SEGPPLTSFR PQCSFMGMVI SHDMLLGRWR LSLELFGRVF MEDVGAEPGS ILTELGGFEV
KESKFRREME KLRNQQSRDL SLEVDRDRDL LIQQTMRQLN NHFGRRCATT PMAVHRVKVT
FKDEPGEGSG VARSFYTAIA QAFLSNEKLP NLECIQNANK GTHTSLMQRL RNRGERDRER
EREREMRRSS GLRAGSRRDR DRDFRRQLSI DTRPFRPASE GNPSDDPEPL PAHRQALGER
LYPRVQAMQP AFASKITGML LELSPAQLLL LLASEDSLRA RVDEAMELII AHGRENGADS
ILDLGLVDSS EKVQQENRKR HGSSRSVVDM DLDDTDDGDD NAPLFYQPGK RGFYTPRPGK
NTEARLNCFR NIGRILGLCL LQNELCPITL NRHVIKVLLG RKVNWHDFAF FDPVMYESLR
QLILASQSSD ADAVFSAMDL AFAIDLCKEE GGGQVELIPN GVNIPVTPQN VYEYVRKYAE
HRMLVVAEQP LHAMRKGLLD VLPKNSLEDL TAEDFRLLVN GCGEVNVQML ISFTSFNDES
GENAEKLLQF KRWFWSIVEK MSMTERQDLV YFWTSSPSLP ASEEGFQPMP SITIRPPDDQ
HLPTANTCIS RLYVPLYSSK QILKQKLLLA IKTKNFGFV
