UBR2_HUMAN
ID UBR2_HUMAN Reviewed; 1755 AA.
AC Q8IWV8; O15057; Q4VXK2; Q5TFH6; Q6P2I2; Q6ZUD0;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=E3 ubiquitin-protein ligase UBR2;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q6WKZ8};
DE AltName: Full=N-recognin-2;
DE AltName: Full=RING-type E3 ubiquitin transferase UBR2;
DE AltName: Full=Ubiquitin-protein ligase E3-alpha-2;
DE AltName: Full=Ubiquitin-protein ligase E3-alpha-II;
GN Name=UBR2; Synonyms=C6orf133, KIAA0349;
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), TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=15548684; DOI=10.1158/0008-5472.can-04-2102;
RA Kwak K.S., Zhou X., Solomon V., Baracos V.E., Davis J., Bannon A.W.,
RA Boyle W.J., Lacey D.L., Han H.Q.;
RT "Regulation of protein catabolism by muscle-specific and cytokine-inducible
RT ubiquitin ligase E3alpha-II during cancer cachexia.";
RL Cancer Res. 64:8193-8198(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ovary;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 481-1755 (ISOFORMS 1/4), AND
RP VARIANT THR-1095.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [6]
RP INTERACTION WITH RECQL4, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15317757; DOI=10.1093/hmg/ddh269;
RA Yin J., Kwon Y.T., Varshavsky A., Wang W.;
RT "RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes,
RT interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway.";
RL Hum. Mol. Genet. 13:2421-2430(2004).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16311597; DOI=10.1038/ng1681;
RA Zenker M., Mayerle J., Lerch M.M., Tagariello A., Zerres K., Durie P.R.,
RA Beier M., Hulskamp G., Guzman C., Rehder H., Beemer F.A., Hamel B.C.J.,
RA Vanlieferinghen P., Gershoni-Baruch R., Vieira M.W., Dumic M.,
RA Auslender R., Gil-da-Silva-Lopes V.L., Steinlicht S., Rauh M., Shalev S.A.,
RA Thiel C., Winterpacht A., Kwon Y.T., Varshavsky A., Reis A.;
RT "Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes
RT pancreatic dysfunction, malformations and mental retardation (Johanson-
RT Blizzard syndrome).";
RL Nat. Genet. 37:1345-1350(2005).
RN [8]
RP 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 [9]
RP IDENTIFICATION BY 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 [10]
RP FUNCTION.
RX PubMed=20298436; DOI=10.1111/j.1365-2443.2010.01385.x;
RA Kume K., Iizumi Y., Shimada M., Ito Y., Kishi T., Yamaguchi Y., Handa H.;
RT "Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the
RT leucine-mTOR signaling pathway.";
RL Genes Cells 15:339-349(2010).
RN [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP 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 [15]
RP INTERACTION WITH CASP8.
RX PubMed=28602583; DOI=10.1016/j.devcel.2017.05.013;
RA Weaver B.P., Weaver Y.M., Mitani S., Han M.;
RT "Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and
RT Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic
RT Development.";
RL Dev. Cell 41:665-673(2017).
RN [16]
RP INTERACTION WITH ATXN3.
RX PubMed=30455355; DOI=10.1074/jbc.ra118.005801;
RA Weishaeupl D., Schneider J., Peixoto Pinheiro B., Ruess C., Dold S.M.,
RA von Zweydorf F., Gloeckner C.J., Schmidt J., Riess O., Schmidt T.;
RT "Physiological and pathophysiological characteristics of ataxin-3
RT isoforms.";
RL J. Biol. Chem. 294:644-661(2019).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 98-167 ALONE AND IN COMPLEX WITH
RP N-END RULE PEPTIDE, UBR-TYPE ZINC FINGER, AND FUNCTION.
RX PubMed=20835242; DOI=10.1038/nsmb.1894;
RA Matta-Camacho E., Kozlov G., Li F.F., Gehring K.;
RT "Structural basis of substrate recognition and specificity in the N-end
RT rule pathway.";
RL Nat. Struct. Mol. Biol. 17:1182-1187(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which is a component of the N-end
CC rule pathway (PubMed:15548684, PubMed:20835242). Recognizes and binds
CC to proteins bearing specific N-terminal residues that are destabilizing
CC according to the N-end rule, leading to their ubiquitination and
CC subsequent degradation (By similarity). Plays a critical role in
CC chromatin inactivation and chromosome-wide transcriptional silencing
CC during meiosis via ubiquitination of histone H2A (By similarity). Binds
CC leucine and is a negative regulator of the leucine-mTOR signaling
CC pathway, thereby controlling cell growth (PubMed:20298436). Required
CC for spermatogenesis, promotes, with Tex19.1, SPO11-dependent
CC recombination foci to accumulate and drive robust homologous chromosome
CC synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon
CC encoded, LIRE1, which induces degradation, inhibiting LINE-1
CC retrotransposon mobilization (By similarity). Catalyzes ubiquitination
CC and degradation of the N-terminal part of NLRP1 following NLRP1
CC activation by pathogens and other damage-associated signals:
CC ubiquitination promotes degradation of the N-terminal part and
CC subsequent release of the cleaved C-terminal part of NLRP1, which
CC polymerizes and forms the NLRP1 inflammasome followed by host cell
CC pyroptosis (By similarity). {ECO:0000250|UniProtKB:Q6WKZ8,
CC ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:20298436,
CC ECO:0000269|PubMed:20835242}.
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=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q6WKZ8};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q6WKZ8}.
CC -!- SUBUNIT: Interacts with UBE2B; promotes the UBE2B-H2A interaction and
CC the ubiquitination of histone H2A by UBE2B and UBR2 (By similarity).
CC Interacts with RECQL4 (PubMed:15317757, PubMed:20835242). Interacts
CC with TEX19; does not lead to TEX19 degradation and stabilizes it (By
CC similarity). Interacts with CASP8 (PubMed:28602583). Interacts with
CC ATXN3 (PubMed:30455355). Interacts with UBE2O (By similarity).
CC {ECO:0000250|UniProtKB:Q6WKZ8, ECO:0000269|PubMed:15317757,
CC ECO:0000269|PubMed:20835242, ECO:0000269|PubMed:28602583,
CC ECO:0000269|PubMed:30455355}.
CC -!- INTERACTION:
CC Q8IWV8; P12504: vif; Xeno; NbExp=3; IntAct=EBI-1237260, EBI-779991;
CC Q8IWV8-2; Q16512: PKN1; NbExp=3; IntAct=EBI-17923957, EBI-602382;
CC Q8IWV8-2; P51687: SUOX; NbExp=3; IntAct=EBI-17923957, EBI-3921347;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6WKZ8}.
CC Chromosome {ECO:0000250|UniProtKB:Q6WKZ8}. Note=Associated with
CC chromatin during meiosis. {ECO:0000250|UniProtKB:Q6WKZ8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8IWV8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IWV8-2; Sequence=VSP_015167, VSP_015168;
CC Name=3;
CC IsoId=Q8IWV8-3; Sequence=VSP_015166, VSP_015169, VSP_015170,
CC VSP_015171;
CC Name=4;
CC IsoId=Q8IWV8-4; Sequence=VSP_017130;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in skeletal
CC muscle, kidney and pancreas. Present in acinar cells of the pancreas
CC (at protein level). {ECO:0000269|PubMed:15548684,
CC ECO:0000269|PubMed:16311597}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal pancreas.
CC {ECO:0000269|PubMed:16311597}.
CC -!- DOMAIN: The RING-H2 zinc finger is an atypical RING finger with a His
CC ligand in place of the fourth Cys of the classical motif.
CC {ECO:0000269|PubMed:20835242}.
CC -!- DOMAIN: The UBR-type zinc finger forms a pocket that mediates
CC recognition of type 1 N-degrons. It exhibits preference for Arginine in
CC first position, has poor affinity for histidine, and doesn't bind
CC acetylated peptides. {ECO:0000269|PubMed:20835242}.
CC -!- MISCELLANEOUS: [Isoform 4]: Derived from mouse cDNA data.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the UBR1 family. {ECO:0000305}.
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DR EMBL; AY061884; AAL32101.1; -; mRNA.
DR EMBL; AK125795; BAC86295.1; -; mRNA.
DR EMBL; AL049843; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391814; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024217; AAH24217.1; -; mRNA.
DR EMBL; BC064512; AAH64512.1; -; mRNA.
DR EMBL; AB002347; BAA20806.1; -; mRNA.
DR CCDS; CCDS4870.1; -. [Q8IWV8-1]
DR CCDS; CCDS55001.1; -. [Q8IWV8-2]
DR CCDS; CCDS87404.1; -. [Q8IWV8-4]
DR RefSeq; NP_001171730.1; NM_001184801.1. [Q8IWV8-2]
DR RefSeq; NP_056070.1; NM_015255.2. [Q8IWV8-1]
DR RefSeq; XP_005249022.1; XM_005248965.4.
DR PDB; 3NY2; X-ray; 2.61 A; A/B/C/D/E/F/G/H=98-167.
DR PDB; 3NY3; X-ray; 1.60 A; A=98-167.
DR PDB; 5TDA; X-ray; 0.79 A; A=98-168.
DR PDB; 5TDB; X-ray; 1.10 A; A=98-168.
DR PDB; 5TDD; X-ray; 1.55 A; A=98-168.
DR PDB; 5UM3; X-ray; 1.20 A; A=98-167.
DR PDBsum; 3NY2; -.
DR PDBsum; 3NY3; -.
DR PDBsum; 5TDA; -.
DR PDBsum; 5TDB; -.
DR PDBsum; 5TDD; -.
DR PDBsum; 5UM3; -.
DR AlphaFoldDB; Q8IWV8; -.
DR BMRB; Q8IWV8; -.
DR SMR; Q8IWV8; -.
DR BioGRID; 116896; 150.
DR DIP; DIP-38165N; -.
DR IntAct; Q8IWV8; 51.
DR MINT; Q8IWV8; -.
DR STRING; 9606.ENSP00000361990; -.
DR iPTMnet; Q8IWV8; -.
DR PhosphoSitePlus; Q8IWV8; -.
DR BioMuta; UBR2; -.
DR DMDM; 73622073; -.
DR EPD; Q8IWV8; -.
DR jPOST; Q8IWV8; -.
DR MassIVE; Q8IWV8; -.
DR MaxQB; Q8IWV8; -.
DR PaxDb; Q8IWV8; -.
DR PeptideAtlas; Q8IWV8; -.
DR PRIDE; Q8IWV8; -.
DR ProteomicsDB; 70909; -. [Q8IWV8-1]
DR ProteomicsDB; 70910; -. [Q8IWV8-2]
DR ProteomicsDB; 70911; -. [Q8IWV8-3]
DR ProteomicsDB; 70912; -. [Q8IWV8-4]
DR Antibodypedia; 30162; 224 antibodies from 32 providers.
DR DNASU; 23304; -.
DR Ensembl; ENST00000372899.6; ENSP00000361990.1; ENSG00000024048.11. [Q8IWV8-1]
DR Ensembl; ENST00000372901.2; ENSP00000361992.1; ENSG00000024048.11. [Q8IWV8-4]
DR Ensembl; ENST00000372903.6; ENSP00000361994.2; ENSG00000024048.11. [Q8IWV8-2]
DR GeneID; 23304; -.
DR KEGG; hsa:23304; -.
DR MANE-Select; ENST00000372901.2; ENSP00000361992.1; NM_001363705.2; NP_001350634.1. [Q8IWV8-4]
DR UCSC; uc003osf.4; human. [Q8IWV8-1]
DR CTD; 23304; -.
DR DisGeNET; 23304; -.
DR GeneCards; UBR2; -.
DR HGNC; HGNC:21289; UBR2.
DR HPA; ENSG00000024048; Low tissue specificity.
DR MIM; 609134; gene.
DR neXtProt; NX_Q8IWV8; -.
DR OpenTargets; ENSG00000024048; -.
DR PharmGKB; PA128394621; -.
DR VEuPathDB; HostDB:ENSG00000024048; -.
DR eggNOG; KOG1140; Eukaryota.
DR GeneTree; ENSGT00950000183075; -.
DR HOGENOM; CLU_055226_0_0_1; -.
DR InParanoid; Q8IWV8; -.
DR OMA; ILCQEDQ; -.
DR OrthoDB; 81415at2759; -.
DR PhylomeDB; Q8IWV8; -.
DR TreeFam; TF323875; -.
DR PathwayCommons; Q8IWV8; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8IWV8; -.
DR SIGNOR; Q8IWV8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23304; 9 hits in 1121 CRISPR screens.
DR ChiTaRS; UBR2; human.
DR EvolutionaryTrace; Q8IWV8; -.
DR GeneWiki; UBR2; -.
DR GenomeRNAi; 23304; -.
DR Pharos; Q8IWV8; Tbio.
DR PRO; PR:Q8IWV8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8IWV8; protein.
DR Bgee; ENSG00000024048; Expressed in secondary oocyte and 209 other tissues.
DR Genevisible; Q8IWV8; HS.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0070728; F:leucine binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071233; P:cellular response to leucine; IDA:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:0033522; P:histone H2A ubiquitination; ISS:UniProtKB.
DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl.
DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007131; P:reciprocal meiotic recombination; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0071596; P:ubiquitin-dependent protein catabolic process via the N-end rule pathway; IBA:GO_Central.
DR Gene3D; 1.10.10.2670; -; 1.
DR Gene3D; 3.30.1390.10; -; 1.
DR InterPro; IPR003769; ClpS_core.
DR InterPro; IPR042065; E3_ELL-like.
DR InterPro; IPR044046; E3_ligase_UBR-like_C.
DR InterPro; IPR014719; Ribosomal_L7/12_C/ClpS-like.
DR InterPro; IPR039164; UBR1-like.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR InterPro; IPR003126; Znf_UBR.
DR PANTHER; PTHR21497; PTHR21497; 1.
DR Pfam; PF02617; ClpS; 1.
DR Pfam; PF18995; PRT6_C; 1.
DR Pfam; PF02207; zf-UBR; 1.
DR SMART; SM00396; ZnF_UBR1; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF54736; SSF54736; 1.
DR PROSITE; PS51157; ZF_UBR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosome; Coiled coil;
KW Metal-binding; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..1755
FT /note="E3 ubiquitin-protein ligase UBR2"
FT /id="PRO_0000056140"
FT ZN_FING 97..168
FT /note="UBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00508"
FT ZN_FING 1108..1214
FT /note="RING-type; atypical"
FT REGION 1004..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1261..1287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1019..1054
FT /evidence="ECO:0000255"
FT COMPBIAS 1018..1034
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1261..1279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT VAR_SEQ 1..496
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015166"
FT VAR_SEQ 397..439
FT /note="QQLQRDFMEDDHERAVSVTALSVQFFTAPTLARMLITEENLMS -> ERLQS
FT DYVTDDHDREFSVADLSVQIFTVPSLFSISAGRSGSPL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015167"
FT VAR_SEQ 397..426
FT /note="QQLQRDFMEDDHERAVSVTALSVQFFTAPT -> ERLQSDYVTDDHDREFSV
FT ADLSVQIFTVPS (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_017130"
FT VAR_SEQ 440..1755
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015168"
FT VAR_SEQ 497..514
FT /note="RQKFLEGFDAFLELLKCM -> MYAGNIPIYKTESRSRNE (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015169"
FT VAR_SEQ 1022..1071
FT /note="SSRDKDKAERKRKAEIARLRREKIMAQMSEMQRHFIDENKELFQQTLELD
FT -> HNFRVQGTKTKLRGREKQRLPDCAEKRSWLRCLKCSGILLMKTKNSFSRH (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015170"
FT VAR_SEQ 1072..1755
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015171"
FT VARIANT 172
FT /note="E -> D (in dbSNP:rs6905054)"
FT /id="VAR_052117"
FT VARIANT 1095
FT /note="A -> P (in dbSNP:rs6917033)"
FT /id="VAR_059816"
FT VARIANT 1095
FT /note="A -> S (in dbSNP:rs6917033)"
FT /id="VAR_059817"
FT VARIANT 1095
FT /note="A -> T (in dbSNP:rs6917033)"
FT /evidence="ECO:0000269|PubMed:9205841"
FT /id="VAR_023283"
FT CONFLICT 864
FT /note="K -> R (in Ref. 2; BAC86295)"
FT /evidence="ECO:0000305"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:5TDA"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:5TDA"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:5TDA"
FT HELIX 125..129
FT /evidence="ECO:0007829|PDB:5TDA"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:5TDA"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:5TDA"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:5TDA"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:5TDA"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:5TDA"
SQ SEQUENCE 1755 AA; 200538 MW; 04B14FCB13E21808 CRC64;
MASELEPEVQ AIDRSLLECS AEEIAGKWLQ ATDLTREVYQ HLAHYVPKIY CRGPNPFPQK
EDMLAQHVLL GPMEWYLCGE DPAFGFPKLE QANKPSHLCG RVFKVGEPTY SCRDCAVDPT
CVLCMECFLG SIHRDHRYRM TTSGGGGFCD CGDTEAWKEG PYCQKHELNT SEIEEEEDPL
VHLSEDVIAR TYNIFAITFR YAVEILTWEK ESELPADLEM VEKSDTYYCM LFNDEVHTYE
QVIYTLQKAV NCTQKEAIGF ATTVDRDGRR SVRYGDFQYC EQAKSVIVRN TSRQTKPLKV
QVMHSSIVAH QNFGLKLLSW LGSIIGYSDG LRRILCQVGL QEGPDGENSS LVDRLMLSDS
KLWKGARSVY HQLFMSSLLM DLKYKKLFAV RFAKNYQQLQ RDFMEDDHER AVSVTALSVQ
FFTAPTLARM LITEENLMSI IIKTFMDHLR HRDAQGRFQF ERYTALQAFK FRRVQSLILD
LKYVLISKPT EWSDELRQKF LEGFDAFLEL LKCMQGMDPI TRQVGQHIEM EPEWEAAFTL
QMKLTHVISM MQDWCASDEK VLIEAYKKCL AVLMQCHGGY TDGEQPITLS ICGHSVETIR
YCVSQEKVSI HLPVSRLLAG LHVLLSKSEV AYKFPELLPL SELSPPMLIE HPLRCLVLCA
QVHAGMWRRN GFSLVNQIYY YHNVKCRREM FDKDVVMLQT GVSMMDPNHF LMIMLSRFEL
YQIFSTPDYG KRFSSEITHK DVVQQNNTLI EEMLYLIIML VGERFSPGVG QVNATDEIKR
EIIHQLSIKP MAHSELVKSL PEDENKETGM ESVIEAVAHF KKPGLTGRGM YELKPECAKE
FNLYFYHFSR AEQSKAEEAQ RKLKRQNRED TALPPPVLPP FCPLFASLVN ILQSDVMLCI
MGTILQWAVE HNGYAWSESM LQRVLHLIGM ALQEEKQHLE NVTEEHVVTF TFTQKISKPG
EAPKNSPSIL AMLETLQNAP YLEVHKDMIR WILKTFNAVK KMRESSPTSP VAETEGTIME
ESSRDKDKAE RKRKAEIARL RREKIMAQMS EMQRHFIDEN KELFQQTLEL DASTSAVLDH
SPVASDMTLT ALGPAQTQVP EQRQFVTCIL CQEEQEVKVE SRAMVLAAFV QRSTVLSKNR
SKFIQDPEKY DPLFMHPDLS CGTHTSSCGH IMHAHCWQRY FDSVQAKEQR RQQRLRLHTS
YDVENGEFLC PLCECLSNTV IPLLLPPRNI FNNRLNFSDQ PNLTQWIRTI SQQIKALQFL
RKEESTPNNA STKNSENVDE LQLPEGFRPD FRPKIPYSES IKEMLTTFGT ATYKVGLKVH
PNEEDPRVPI MCWGSCAYTI QSIERILSDE DKPLFGPLPC RLDDCLRSLT RFAAAHWTVA
SVSVVQGHFC KLFASLVPND SHEELPCILD IDMFHLLVGL VLAFPALQCQ DFSGISLGTG
DLHIFHLVTM AHIIQILLTS CTEENGMDQE NPPCEEESAV LALYKTLHQY TGSALKEIPS
GWHLWRSVRA GIMPFLKCSA LFFHYLNGVP SPPDIQVPGT SHFEHLCSYL SLPNNLICLF
QENSEIMNSL IESWCRNSEV KRYLEGERDA IRYPRESNKL INLPEDYSSL INQASNFSCP
KSGGDKSRAP TLCLVCGSLL CSQSYCCQTE LEGEDVGACT AHTYSCGSGV GIFLRVRECQ
VLFLAGKTKG CFYSPPYLDD YGETDQGLRR GNPLHLCKER FKKIQKLWHQ HSVTEEIGHA
QEANQTLVGI DWQHL
