ID RING2_HUMAN Reviewed; 336 AA.
AC Q99496; B2RBS7; B3KRH1; Q5TEN1; Q5TEN2;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 27-MAR-2024, entry version 216.
DE RecName: Full=E3 ubiquitin-protein ligase RING2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:21772249, ECO:0000269|PubMed:26151332};
DE AltName: Full=Huntingtin-interacting protein 2-interacting protein 3;
DE Short=HIP2-interacting protein 3;
DE AltName: Full=Protein DinG;
DE AltName: Full=RING finger protein 1B;
DE Short=RING1b;
DE AltName: Full=RING finger protein 2;
DE AltName: Full=RING finger protein BAP-1;
DE AltName: Full=RING-type E3 ubiquitin transferase RING2 {ECO:0000305};
GN Name=RNF2; Synonyms=BAP1, DING, HIPI3, RING1B;
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=Brain;
RA Dyer M.J.S., Abdul-Rauf M., Heward J.M., Cui X., Cleary M.L., Catovsky D.;
RT "Interactions of BCL7A with novel ring finger proteins.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Li S.-F.;
RT "Identification of Bap-1, a protein that binds to integrin and is involved
RT in integrin-mediated signal transduction.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP INTERACTION WITH HIP2, FUNCTION, AND MUTAGENESIS OF CYS-51; CYS-54 AND
RP HIS-69.
RX PubMed=11513855; DOI=10.1016/s0014-5793(01)02689-8;
RA Lee S.-J., Choi J.-Y., Sung Y.-M., Park H., Rhim H., Kang S.;
RT "E3 ligase activity of RING finger proteins that interact with Hip-2, a
RT human ubiquitin-conjugating enzyme.";
RL FEBS Lett. 503:61-64(2001).
RN [8]
RP INTERACTION WITH TFCP2.
RX PubMed=11865070; DOI=10.1128/mcb.22.6.1936-1946.2002;
RA Tuckfield A., Clouston D.R., Wilanowski T.M., Zhao L.-L., Cunningham J.M.,
RA Jane S.M.;
RT "Binding of the RING polycomb proteins to specific target genes in complex
RT with the grainyhead-like family of developmental transcription factors.";
RL Mol. Cell. Biol. 22:1936-1946(2002).
RN [9]
RP IDENTIFICATION IN A PRC1-LIKE HPRC-H COMPLEX.
RX PubMed=12167701; DOI=10.1128/mcb.22.17.6070-6078.2002;
RA Levine S.S., Weiss A., Erdjument-Bromage H., Shao Z., Tempst P.,
RA Kingston R.E.;
RT "The core of the polycomb repressive complex is compositionally and
RT functionally conserved in flies and humans.";
RL Mol. Cell. Biol. 22:6070-6078(2002).
RN [10]
RP IDENTIFICATION IN COMPLEX WITH E2F6; TFDP1; MAX; MGA; EUHMTASE1; BAT8;
RP CBX3; RNF1; MBLR; L3MBTL2 AND YAF2.
RX PubMed=12004135; DOI=10.1126/science.1069861;
RA Ogawa H., Ishiguro K., Gaubatz S., Livingston D.M., Nakatani Y.;
RT "A complex with chromatin modifiers that occupies E2F- and Myc-responsive
RT genes in G0 cells.";
RL Science 296:1132-1136(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A PRC1-LIKE COMPLEX
RP WITH RING1; PHC2 AND BMI1, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP MUTAGENESIS OF HIS-69 AND ARG-70.
RX PubMed=15386022; DOI=10.1038/nature02985;
RA Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R.S.,
RA Zhang Y.;
RT "Role of histone H2A ubiquitination in Polycomb silencing.";
RL Nature 431:873-878(2004).
RN [12]
RP IDENTIFICATION IN THE MLL1/MLL COMPLEX.
RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031;
RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J.,
RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.;
RT "Physical association and coordinate function of the H3 K4
RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.";
RL Cell 121:873-885(2005).
RN [13]
RP FUNCTION.
RX PubMed=16359901; DOI=10.1016/j.molcel.2005.12.002;
RA Cao R., Tsukada Y., Zhang Y.;
RT "Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.";
RL Mol. Cell 20:845-854(2005).
RN [14]
RP INTERACTION WITH RYBP; PCGF1; BCOR AND RING1.
RX PubMed=16943429; DOI=10.1128/mcb.00630-06;
RA Gearhart M.D., Corcoran C.M., Wamstad J.A., Bardwell V.J.;
RT "Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex
RT that is recruited to BCL6 targets.";
RL Mol. Cell. Biol. 26:6880-6889(2006).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-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 [16]
RP IDENTIFICATION IN A PRC1-LIKE COMPLEX, AND INTERACTION WITH PCGF2.
RX PubMed=19636380; DOI=10.1371/journal.pone.0006380;
RA Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K., Nicholls J.,
RA Rodriguez-Niedenfuhr M., Gil J., Peters G.;
RT "Several distinct polycomb complexes regulate and co-localize on the INK4a
RT tumor suppressor locus.";
RL PLoS ONE 4:E6380-E6380(2009).
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 IDENTIFICATION IN A PRC1-LIKE COMPLEX, INTERACTION WITH CBX4; CBX6; CBX7
RP AND CBX8, AND SUBCELLULAR LOCATION.
RX PubMed=21282530; DOI=10.1074/mcp.m110.002642;
RA Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O.;
RT "Interaction proteomics analysis of polycomb proteins defines distinct PRC1
RT Complexes in mammalian cells.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND SER-168, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [20]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH PCGF5;
RP AUTS2; CSNK2B AND RYBP, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF
RP SER-41 AND SER-168, AND PHOSPHORYLATION AT SER-41 AND SER-168.
RX PubMed=25519132; DOI=10.1038/nature13921;
RA Gao Z., Lee P., Stafford J.M., von Schimmelmann M., Schaefer A.,
RA Reinberg D.;
RT "An AUTS2-polycomb complex activates gene expression in the CNS.";
RL Nature 516:349-354(2014).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH PCGF1.
RX PubMed=26687479; DOI=10.1038/srep18388;
RA Oliviero G., Munawar N., Watson A., Streubel G., Manning G., Bardwell V.,
RA Bracken A.P., Cagney G.;
RT "The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a
RT pluripotency sub-network that includes DPPA4, a regulator of
RT embryogenesis.";
RL Sci. Rep. 5:18388-18388(2015).
RN [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-249 AND LYS-323, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [23]
RP INTERACTION WITH NUPR1.
RX PubMed=28720707; DOI=10.1073/pnas.1619932114;
RA Santofimia-Castano P., Rizzuti B., Pey A.L., Soubeyran P., Vidal M.,
RA Urrutia R., Iovanna J.L., Neira J.L.;
RT "Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal
RT region of Polycomb RING1B.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E6332-E6341(2017).
RN [24]
RP INVOLVEMENT IN LUSYAM, VARIANTS LUSYAM HIS-70 AND ARG-82, AND FUNCTION.
RX PubMed=33864376; DOI=10.1093/hmg/ddab110;
RG Undiagnosed Diseases Network;
RA Luo X., Schoch K., Jangam S.V., Bhavana V.H., Graves H.K., Kansagra S.,
RA Jasien J.M., Stong N., Keren B., Mignot C., Ravelli C., Bellen H.J.,
RA Wangler M.F., Shashi V., Yamamoto S.;
RT "Rare deleterious de novo missense variants in Rnf2/Ring2 are associated
RT with a neurodevelopmental disorder with unique clinical features.";
RL Hum. Mol. Genet. 30:1283-1292(2021).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 15-114 IN COMPLEX WITH BMI1 AND
RP ZINC IONS, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBUNIT.
RX PubMed=16714294; DOI=10.1074/jbc.m602461200;
RA Li Z., Cao R., Wang M., Myers M.P., Zhang Y., Xu R.M.;
RT "Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex.";
RL J. Biol. Chem. 281:20643-20649(2006).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 220-330, INTERACTION WITH CBX7,
RP AND MUTAGENESIS OF TYR-262.
RX PubMed=19791798; DOI=10.1021/bi901131u;
RA Bezsonova I., Walker J.R., Bacik J.P., Duan S., Dhe-Paganon S.,
RA Arrowsmith C.H.;
RT "Ring1B contains a ubiquitin-like docking module for interaction with Cbx
RT proteins.";
RL Biochemistry 48:10542-10548(2009).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 223-333 IN COMPLEXES WITH CBX7 AND
RP RYBP, FUNCTION, AND MUTAGENESIS OF TYR-247; HIS-258 AND TYR-262.
RX PubMed=20696397; DOI=10.1016/j.str.2010.04.013;
RA Wang R., Taylor A.B., Leal B.Z., Chadwell L.V., Ilangovan U.,
RA Robinson A.K., Schirf V., Hart P.J., Lafer E.M., Demeler B., Hinck A.P.,
RA McEwen D.G., Kim C.A.;
RT "Polycomb group targeting through different binding partners of RING1B C-
RT terminal domain.";
RL Structure 18:966-975(2010).
RN [28] {ECO:0007744|PDB:3RPG}
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-116 IN COMPLEX WITH ZINC IONS;
RP BMI1 AND UB2D3, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF
RP ASP-56 AND 97-LYS-ARG-98.
RX PubMed=21772249; DOI=10.1038/emboj.2011.243;
RA Bentley M.L., Corn J.E., Dong K.C., Phung Q., Cheung T.K., Cochran A.G.;
RT "Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin
RT ligase complex.";
RL EMBO J. 30:3285-3297(2011).
RN [29] {ECO:0007744|PDB:4R8P}
RP X-RAY CRYSTALLOGRAPHY (3.28 ANGSTROMS) OF 2-116 IN COMPLEX WITH ZINC IONS;
RP THE NUCLEOSOME; BMI1 AND UB2D3, FUNCTION, AND MUTAGENESIS OF ARG-81;
RP LYS-93; LYS-97 AND ARG-98.
RX PubMed=25355358; DOI=10.1038/nature13890;
RA McGinty R.K., Henrici R.C., Tan S.;
RT "Crystal structure of the PRC1 ubiquitylation module bound to the
RT nucleosome.";
RL Nature 514:591-596(2014).
RN [30] {ECO:0007744|PDB:4S3O}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-116 IN COMPLEX WITH ZINC IONS;
RP UB2D3 AND PCGF5, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26151332; DOI=10.1038/ncomms8621;
RA Taherbhoy A.M., Huang O.W., Cochran A.G.;
RT "BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase.";
RL Nat. Commun. 6:7621-7621(2015).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates monoubiquitination
CC of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role
CC in histone code and gene regulation (PubMed:15386022, PubMed:16359901,
CC PubMed:25519132, PubMed:33864376, PubMed:21772249, PubMed:25355358,
CC PubMed:26151332). H2AK119Ub gives a specific tag for epigenetic
CC transcriptional repression and participates in X chromosome
CC inactivation of female mammals. May be involved in the initiation of
CC both imprinted and random X inactivation (By similarity). Essential
CC component of a Polycomb group (PcG) multiprotein PRC1-like complex, a
CC complex class required to maintain the transcriptionally repressive
CC state of many genes, including Hox genes, throughout development
CC (PubMed:16359901, PubMed:26151332). PcG PRC1 complex acts via chromatin
CC remodeling and modification of histones, rendering chromatin heritably
CC changed in its expressibility (PubMed:26151332). E3 ubiquitin-protein
CC ligase activity is enhanced by BMI1/PCGF4 (PubMed:21772249). Acts as
CC the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while
CC RING1 may rather act as a modulator of RNF2/RING2 activity (Probable).
CC Association with the chromosomal DNA is cell-cycle dependent. In
CC resting B- and T-lymphocytes, interaction with AURKB leads to block its
CC activity, thereby maintaining transcription in resting lymphocytes (By
CC similarity). Also acts as a negative regulator of autophagy by
CC mediating ubiquitination of AMBRA1, leading to its subsequent
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q9CQJ4,
CC ECO:0000269|PubMed:11513855, ECO:0000269|PubMed:15386022,
CC ECO:0000269|PubMed:16359901, ECO:0000269|PubMed:16714294,
CC ECO:0000269|PubMed:20696397, ECO:0000269|PubMed:21772249,
CC ECO:0000269|PubMed:25355358, ECO:0000269|PubMed:25519132,
CC ECO:0000269|PubMed:26151332, ECO:0000269|PubMed:33864376, ECO:0000305}.
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:0000269|PubMed:15386022,
CC ECO:0000269|PubMed:21772249, ECO:0000269|PubMed:26151332};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:21772249,
CC ECO:0000269|PubMed:26151332}.
CC -!- SUBUNIT: Component of chromatin-associated Polycomb (PcG) complexes.
CC Component of a number of PRC1-like complexes; these complexes contain
CC either the polycomb group ring finger protein PCGF1, or PCGF2, or
CC PCGF3, or PCGF4, or PCGF5, or PCGF6 (PubMed:12167701, PubMed:15386022,
CC PubMed:19636380, PubMed:21282530, PubMed:26687479, PubMed:26151332).
CC Part of a complex that contains RNF2, UB2D3 and BMI1; within that
CC complex RNF2 and BMI1 form a tight heterodimer, where UB2D3 interacts
CC only with RNF2 (PubMed:21772249, PubMed:25355358). The complex composed
CC of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with
CC nucleosomal histone H2A (PubMed:21772249). Part of a complex that
CC contains PCGF5, RNF2 and UBE2D3 (PubMed:26151332). Part of a complex
CC that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP (PubMed:25519132).
CC Interacts with RYBP, PCGF2, CBX4, CBX6, CBX7 and CBX8 (PubMed:19636380,
CC PubMed:21282530, PubMed:19791798, PubMed:20696397). Interacts with
CC RNF1/RING1, BMI1 and PHC2 (PubMed:15386022, PubMed:16714294).
CC Interaction with RYBP and CBX7 is mutually exclusive; both compete for
CC the same binding site on RNF2 (By similarity). Component of repressive
CC BCOR complex containing a Polycomb group subcomplex at least composed
CC of RYBP, PCGF1, BCOR and RING1 (PubMed:16943429). Interacts with CBX2
CC and PHC1. Interacts with CHTOP. Interacts with AURKB (By similarity).
CC Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX,
CC TFDP1, CBX3, BAT8, EUHMTASE1, RNF1/RING1, RNF2/RING2, MBLR, L3MBTL2 and
CC YAF2 (PubMed:12004135). Component of some MLL1/MLL complex, at least
CC composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and
CC RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70,
CC INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31,
CC RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9
CC and TEX10 (PubMed:15960975). Interacts with RYBP, HIP2 and TFCP2
CC (PubMed:11513855, PubMed:11865070, PubMed:20696397). Interacts with
CC NUPR1 (PubMed:28720707). {ECO:0000250|UniProtKB:Q9CQJ4,
CC ECO:0000269|PubMed:11513855, ECO:0000269|PubMed:11865070,
CC ECO:0000269|PubMed:12004135, ECO:0000269|PubMed:12167701,
CC ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:15960975,
CC ECO:0000269|PubMed:16714294, ECO:0000269|PubMed:16943429,
CC ECO:0000269|PubMed:19636380, ECO:0000269|PubMed:19791798,
CC ECO:0000269|PubMed:21282530, ECO:0000269|PubMed:21772249,
CC ECO:0000269|PubMed:25355358, ECO:0000269|PubMed:25519132,
CC ECO:0000269|PubMed:26151332, ECO:0000269|PubMed:26687479,
CC ECO:0000269|PubMed:28720707}.
CC -!- INTERACTION:
CC Q99496; P08183: ABCB1; NbExp=2; IntAct=EBI-722416, EBI-1057359;
CC Q99496; P54253: ATXN1; NbExp=6; IntAct=EBI-722416, EBI-930964;
CC Q99496; Q8WXX7: AUTS2; NbExp=7; IntAct=EBI-722416, EBI-2875359;
CC Q99496; P35226: BMI1; NbExp=21; IntAct=EBI-722416, EBI-2341576;
CC Q99496; O00257: CBX4; NbExp=5; IntAct=EBI-722416, EBI-722425;
CC Q99496; O00257-3: CBX4; NbExp=2; IntAct=EBI-722416, EBI-4392727;
CC Q99496; O95503: CBX6; NbExp=7; IntAct=EBI-722416, EBI-3951758;
CC Q99496; O95931: CBX7; NbExp=15; IntAct=EBI-722416, EBI-3923843;
CC Q99496; Q9HC52: CBX8; NbExp=11; IntAct=EBI-722416, EBI-712912;
CC Q99496; P68400: CSNK2A1; NbExp=4; IntAct=EBI-722416, EBI-347804;
CC Q99496; P67870: CSNK2B; NbExp=2; IntAct=EBI-722416, EBI-348169;
CC Q99496; P0C0S8: H2AC17; NbExp=5; IntAct=EBI-722416, EBI-1390628;
CC Q99496; Q9H7Z6: KAT8; NbExp=2; IntAct=EBI-722416, EBI-896414;
CC Q99496; Q9BSM1: PCGF1; NbExp=15; IntAct=EBI-722416, EBI-749901;
CC Q99496; P35227: PCGF2; NbExp=16; IntAct=EBI-722416, EBI-2129767;
CC Q99496; Q3KNV8: PCGF3; NbExp=5; IntAct=EBI-722416, EBI-2339807;
CC Q99496; Q3KNV8-2: PCGF3; NbExp=3; IntAct=EBI-722416, EBI-12818023;
CC Q99496; Q86SE9: PCGF5; NbExp=9; IntAct=EBI-722416, EBI-2827999;
CC Q99496; Q9BYE7: PCGF6; NbExp=6; IntAct=EBI-722416, EBI-1048026;
CC Q99496; P49810: PSEN2; NbExp=3; IntAct=EBI-722416, EBI-2010251;
CC Q99496; Q06587: RING1; NbExp=6; IntAct=EBI-722416, EBI-752313;
CC Q99496; Q8N488: RYBP; NbExp=20; IntAct=EBI-722416, EBI-752324;
CC Q99496; P51668: UBE2D1; NbExp=4; IntAct=EBI-722416, EBI-743540;
CC Q99496; P62837: UBE2D2; NbExp=4; IntAct=EBI-722416, EBI-347677;
CC Q99496; P61077: UBE2D3; NbExp=6; IntAct=EBI-722416, EBI-348268;
CC Q99496; Q9Y2X8: UBE2D4; NbExp=4; IntAct=EBI-722416, EBI-745527;
CC Q99496; Q96LR5: UBE2E2; NbExp=6; IntAct=EBI-722416, EBI-2129763;
CC Q99496; Q969T4: UBE2E3; NbExp=6; IntAct=EBI-722416, EBI-348496;
CC Q99496; P61086: UBE2K; NbExp=3; IntAct=EBI-722416, EBI-473850;
CC Q99496; P51784: USP11; NbExp=4; IntAct=EBI-722416, EBI-306876;
CC Q99496; Q93009: USP7; NbExp=5; IntAct=EBI-722416, EBI-302474;
CC Q99496; Q8IY57-5: YAF2; NbExp=5; IntAct=EBI-722416, EBI-12111538;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21282530}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9CQJ4}. Chromosome
CC {ECO:0000250|UniProtKB:Q9CQJ4}. Note=Enriched on inactive X chromosome
CC (Xi) in female trophoblast stem (TS) cells as well as differentiating
CC embryonic stem (ES) cells. The enrichment on Xi is transient during TS
CC and ES cell differentiation. The association with Xi is mitotically
CC stable in non-differentiated TS cells. {ECO:0000250|UniProtKB:Q9CQJ4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99496-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99496-2; Sequence=VSP_055439;
CC -!- PTM: Monoubiquitinated, by auto-ubiquitination (By similarity).
CC Polyubiquitinated in the presence of UBE2D3 (in vitro)
CC (PubMed:26151332). {ECO:0000250|UniProtKB:Q9CQJ4,
CC ECO:0000269|PubMed:26151332}.
CC -!- DISEASE: Luo-Schoch-Yamamoto syndrome (LUSYAM) [MIM:619460]: An
CC autosomal dominant disorder characterized by intrauterine growth
CC retardation, severe intellectual disability, behavioral problems,
CC early-onset seizures, feeding difficulties, and dysmorphic features.
CC White matter abnormalities and delayed myelination are observed on
CC brain imaging. {ECO:0000269|PubMed:33864376}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The hPRC-H complex purification reported probably
CC presents a mixture of different PRC1-like complexes.
CC {ECO:0000269|PubMed:12167701}.
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DR EMBL; Y10571; CAA71596.1; -; mRNA.
DR EMBL; AF141327; AAD29717.1; -; mRNA.
DR EMBL; AK091574; BAG52383.1; -; mRNA.
DR EMBL; AK314793; BAG37324.1; -; mRNA.
DR EMBL; AL109865; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91187.1; -; Genomic_DNA.
DR EMBL; CH471067; EAW91188.1; -; Genomic_DNA.
DR EMBL; BC012583; AAH12583.1; -; mRNA.
DR CCDS; CCDS1365.1; -. [Q99496-1]
DR RefSeq; NP_009143.1; NM_007212.3. [Q99496-1]
DR RefSeq; XP_011508153.1; XM_011509851.2. [Q99496-1]
DR RefSeq; XP_011508154.1; XM_011509852.2. [Q99496-1]
DR PDB; 2H0D; X-ray; 2.50 A; B=15-114.
DR PDB; 3GS2; X-ray; 1.70 A; A/C=223-333.
DR PDB; 3H8H; X-ray; 2.00 A; A=220-330.
DR PDB; 3IXS; X-ray; 1.70 A; A/C/E/G/I/K=223-333.
DR PDB; 3RPG; X-ray; 2.65 A; C=1-116.
DR PDB; 4R8P; X-ray; 3.28 A; L/N=2-116.
DR PDB; 4S3O; X-ray; 2.00 A; B/E=1-116.
DR PDB; 6WI7; X-ray; 1.70 A; A=10-116.
DR PDB; 6WI8; X-ray; 3.09 A; A/B=10-116.
DR PDB; 7ND1; NMR; -; A=10-116.
DR PDB; 8GRM; EM; 3.05 A; N=16-116.
DR PDBsum; 2H0D; -.
DR PDBsum; 3GS2; -.
DR PDBsum; 3H8H; -.
DR PDBsum; 3IXS; -.
DR PDBsum; 3RPG; -.
DR PDBsum; 4R8P; -.
DR PDBsum; 4S3O; -.
DR PDBsum; 6WI7; -.
DR PDBsum; 6WI8; -.
DR PDBsum; 7ND1; -.
DR PDBsum; 8GRM; -.
DR AlphaFoldDB; Q99496; -.
DR BMRB; Q99496; -.
DR EMDB; EMD-34207; -.
DR SMR; Q99496; -.
DR BioGRID; 111972; 815.
DR ComplexPortal; CPX-2272; Non-canonical polycomb repressive complex 1.1, RING2-PCGF1-YAF2 variant.
DR ComplexPortal; CPX-2276; Non-canonical polycomb repressive complex 1.2, RNF2-RYBP variant.
DR ComplexPortal; CPX-2280; Non-canonical polycomb repressive complex 1.2, RNF2-YAF2 variant.
DR ComplexPortal; CPX-2282; Non-canonical polycomb repressive complex 1.4, RNF2-YAF2 variant.
DR ComplexPortal; CPX-2291; Non-canonical polycomb repressive complex 1.3, RING2-RYBP-CKIIA2 variant.
DR ComplexPortal; CPX-2292; Non-canonical polycomb repressive complex 1.3, RING2-RYBP-CKIIA1-A2 variant.
DR ComplexPortal; CPX-2295; Non-canonical polycomb repressive complex 1.3, RING2-RYBP-CKIIA1 variant.
DR ComplexPortal; CPX-2296; Non-canonical polycomb repressive complex 1.3, RING2-YAF2-CKIIA2 variant.
DR ComplexPortal; CPX-2297; Non-canonical polycomb repressive complex 1.3, RING2-YAF2-CKIIA1-A2 variant.
DR ComplexPortal; CPX-2298; Non-canonical polycomb repressive complex 1.3, RING2-YAF2-CKIIA1 variant.
DR ComplexPortal; CPX-2555; Non-canonical polycomb repressive complex 1.6, RING2-RYBP variant.
DR ComplexPortal; CPX-2557; Non-canonical polycomb repressive complex 1.6, RING2-YAF2 variant.
DR ComplexPortal; CPX-2571; Non-canonical polycomb repressive complex 1.4, RNF2-RYBP variant.
DR ComplexPortal; CPX-2627; Non-canonical polycomb repressive complex 1.1, RING2-PCGF1-RYBP variant.
DR ComplexPortal; CPX-7519; Polycomb repressive complex 1, RING2-PCGF2-CBX2-PHC1 variant.
DR ComplexPortal; CPX-7522; Polycomb repressive complex 1, RING2-PCGF2-CBX2-PHC2 variant.
DR ComplexPortal; CPX-7523; Polycomb repressive complex 1, RING2-PCGF2-CBX2-PHC3 variant.
DR ComplexPortal; CPX-7524; Polycomb repressive complex 1, RING2-PCGF2-CBX4-PHC1 variant.
DR ComplexPortal; CPX-7525; Polycomb repressive complex 1, RING2-PCGF2-CBX4-PHC3 variant.
DR ComplexPortal; CPX-7526; Polycomb repressive complex 1, RING2-PCGF2-CBX4-PHC2 variant.
DR ComplexPortal; CPX-7527; Polycomb repressive complex 1, RING2-PCGF2-CBX6-PHC1 variant.
DR ComplexPortal; CPX-7528; Polycomb repressive complex 1, RING2-PCGF2-CBX6-PHC2 variant.
DR ComplexPortal; CPX-7529; Polycomb repressive complex 1, RING2-PCGF2-CBX6-PHC3 variant.
DR ComplexPortal; CPX-7530; Polycomb repressive complex 1, RING2-PCGF2-CBX7-PHC1 variant.
DR ComplexPortal; CPX-7531; Polycomb repressive complex 1, RING2-PCGF2-CBX7-PHC2 variant.
DR ComplexPortal; CPX-7532; Polycomb repressive complex 1, RING2-PCGF2-CBX7-PHC3 variant.
DR ComplexPortal; CPX-7533; Polycomb repressive complex 1, RING2-PCGF2-CBX8-PHC1 variant.
DR ComplexPortal; CPX-7534; Polycomb repressive complex 1, RING2-PCGF2-CBX8-PHC2 variant.
DR ComplexPortal; CPX-7535; Polycomb repressive complex 1, RING2-PCGF2-CBX8-PHC3 variant.
DR ComplexPortal; CPX-7541; Polycomb repressive complex 1, RING2-PCGF4-CBX2-PHC1 variant.
DR ComplexPortal; CPX-7542; Polycomb repressive complex 1, RING2-PCGF4-CBX2-PHC2 variant.
DR ComplexPortal; CPX-7544; Polycomb repressive complex 1, RING2-PCGF4-CBX2-PHC3 variant.
DR ComplexPortal; CPX-7545; Polycomb repressive complex 1, RING2-PCGF4-CBX4-PHC1 variant.
DR ComplexPortal; CPX-7546; Polycomb repressive complex 1, RING2-PCGF4-CBX4-PHC2 variant.
DR ComplexPortal; CPX-7547; Polycomb repressive complex 1, RING2-PCGF4-CBX4-PHC3 variant.
DR ComplexPortal; CPX-7548; Polycomb repressive complex 1, RING2-PCGF4-CBX6-PHC1 variant.
DR ComplexPortal; CPX-7549; Polycomb repressive complex 1, RING2-PCGF4-CBX6-PHC2 variant.
DR ComplexPortal; CPX-7550; Polycomb repressive complex 1, RING2-PCGF4-CBX6-PHC3 variant.
DR ComplexPortal; CPX-7551; Polycomb repressive complex 1, RING2-PCGF4-CBX7-PHC1 variant.
DR ComplexPortal; CPX-7552; Polycomb repressive complex 1, RING2-PCGF4-CBX7-PHC2 variant.
DR ComplexPortal; CPX-7553; Polycomb repressive complex 1, RING2-PCGF4-CBX7-PHC3 variant.
DR ComplexPortal; CPX-7554; Polycomb repressive complex 1, RING2-PCGF4-CBX8-PHC1 variant.
DR ComplexPortal; CPX-7555; Polycomb repressive complex 1, RING2-PCGF4-CBX8-PHC2 variant.
DR ComplexPortal; CPX-7556; Polycomb repressive complex 1, RING2-PCGF4-CBX8-PHC3 variant.
DR ComplexPortal; CPX-7587; Non-canonical polycomb repressive complex 1.5, RING2-RYBP-CKIIA2 variant.
DR ComplexPortal; CPX-7588; Non-canonical polycomb repressive complex 1.5, RING2-RYBP-CKIIA1-A2 variant.
DR ComplexPortal; CPX-7589; Non-canonical polycomb repressive complex 1.5, RING2-RYBP-CKIIA1 variant.
DR ComplexPortal; CPX-7590; Non-canonical polycomb repressive complex 1.5, RING2-YAF2-CKIIA2 variant.
DR ComplexPortal; CPX-7591; Non-canonical polycomb repressive complex 1.5, RING2-YAF2-CKIIA1-A2 variant.
DR ComplexPortal; CPX-7592; Non-canonical polycomb repressive complex 1.5, RING2-YAF2-CKIIA1 variant.
DR CORUM; Q99496; -.
DR DIP; DIP-40034N; -.
DR IntAct; Q99496; 126.
DR MINT; Q99496; -.
DR STRING; 9606.ENSP00000356480; -.
DR GlyCosmos; Q99496; 1 site, 1 glycan.
DR GlyGen; Q99496; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q99496; -.
DR PhosphoSitePlus; Q99496; -.
DR SwissPalm; Q99496; -.
DR BioMuta; RNF2; -.
DR DMDM; 62901044; -.
DR EPD; Q99496; -.
DR jPOST; Q99496; -.
DR MassIVE; Q99496; -.
DR MaxQB; Q99496; -.
DR PaxDb; 9606-ENSP00000356480; -.
DR PeptideAtlas; Q99496; -.
DR ProteomicsDB; 3602; -.
DR ProteomicsDB; 78297; -. [Q99496-1]
DR Pumba; Q99496; -.
DR Antibodypedia; 20609; 485 antibodies from 44 providers.
DR DNASU; 6045; -.
DR Ensembl; ENST00000367509.8; ENSP00000356479.4; ENSG00000121481.11. [Q99496-2]
DR Ensembl; ENST00000367510.8; ENSP00000356480.3; ENSG00000121481.11. [Q99496-1]
DR GeneID; 6045; -.
DR KEGG; hsa:6045; -.
DR MANE-Select; ENST00000367510.8; ENSP00000356480.3; NM_007212.4; NP_009143.1.
DR UCSC; uc001grc.2; human. [Q99496-1]
DR AGR; HGNC:10061; -.
DR CTD; 6045; -.
DR DisGeNET; 6045; -.
DR GeneCards; RNF2; -.
DR HGNC; HGNC:10061; RNF2.
DR HPA; ENSG00000121481; Low tissue specificity.
DR MalaCards; RNF2; -.
DR MIM; 608985; gene.
DR MIM; 619460; phenotype.
DR neXtProt; NX_Q99496; -.
DR OpenTargets; ENSG00000121481; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA34426; -.
DR VEuPathDB; HostDB:ENSG00000121481; -.
DR eggNOG; KOG0311; Eukaryota.
DR GeneTree; ENSGT00940000154499; -.
DR InParanoid; Q99496; -.
DR OMA; FCIYIAQ; -.
DR OrthoDB; 460116at2759; -.
DR PhylomeDB; Q99496; -.
DR TreeFam; TF105501; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q99496; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-HSA-4570464; SUMOylation of RNA binding proteins.
DR Reactome; R-HSA-4655427; SUMOylation of DNA methylation proteins.
DR Reactome; R-HSA-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR SignaLink; Q99496; -.
DR SIGNOR; Q99496; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 6045; 15 hits in 1195 CRISPR screens.
DR ChiTaRS; RNF2; human.
DR EvolutionaryTrace; Q99496; -.
DR GeneWiki; RNF2; -.
DR GenomeRNAi; 6045; -.
DR Pharos; Q99496; Tbio.
DR PRO; PR:Q99496; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q99496; Protein.
DR Bgee; ENSG00000121481; Expressed in primordial germ cell in gonad and 110 other cell types or tissues.
DR ExpressionAtlas; Q99496; baseline and differential.
DR Genevisible; Q99496; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000791; C:euchromatin; IEA:Ensembl.
DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031519; C:PcG protein complex; IDA:UniProtKB.
DR GO; GO:0035102; C:PRC1 complex; IDA:UniProtKB.
DR GO; GO:0001739; C:sex chromatin; IEA:Ensembl.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0140862; F:histone H2AK119 ubiquitin ligase activity; ISS:UniProtKB.
DR GO; GO:0071535; F:RING-like zinc finger domain binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl.
DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB.
DR GO; GO:0040029; P:epigenetic regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR CDD; cd17167; RAWUL_RING2; 1.
DR CDD; cd16740; RING-HC_RING2; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR032443; RAWUL.
DR InterPro; IPR043540; RING1/RING2.
DR InterPro; IPR037937; RING2_RAWUL_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR46076; E3 UBIQUITIN-PROTEIN LIGASE RING1 / RING 2 FAMILY MEMBER; 1.
DR PANTHER; PTHR46076:SF4; E3 UBIQUITIN-PROTEIN LIGASE RING2; 1.
DR Pfam; PF16207; RAWUL; 1.
DR Pfam; PF13923; zf-C3HC4_2; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosome; Cytoplasm;
KW Disease variant; Epilepsy; Intellectual disability; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..336
FT /note="E3 ubiquitin-protein ligase RING2"
FT /id="PRO_0000056038"
FT ZN_FING 51..91
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 2..179
FT /note="Interaction with HIP2"
FT /evidence="ECO:0000269|PubMed:11513855"
FT REGION 93..98
FT /note="Interaction with nucleosomes via an acidic patch on
FT histone H2A and histone H2B"
FT /evidence="ECO:0000269|PubMed:25355358"
FT REGION 157..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..194
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25519132"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25519132,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 112
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9CQJ4"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 323
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 84..155
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055439"
FT VARIANT 70
FT /note="R -> H (in LUSYAM; dbSNP:rs1651767648)"
FT /evidence="ECO:0000269|PubMed:33864376"
FT /id="VAR_086207"
FT VARIANT 82
FT /note="S -> R (in LUSYAM; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:33864376"
FT /id="VAR_086208"
FT MUTAGEN 41
FT /note="S->A,D: No effect on ubiquitin ligase activity on
FT histone H2A."
FT /evidence="ECO:0000269|PubMed:25519132"
FT MUTAGEN 51
FT /note="C->W: Strong decrease in HIP2-binding; when
FT associated with S-54."
FT /evidence="ECO:0000269|PubMed:11513855"
FT MUTAGEN 54
FT /note="C->S: Strong decrease in HIP2-binding; when
FT associated with W-51."
FT /evidence="ECO:0000269|PubMed:11513855"
FT MUTAGEN 56
FT /note="D->K: Loss of ubiquitin ligase activity on histone
FT H2A."
FT /evidence="ECO:0000269|PubMed:21772249"
FT MUTAGEN 69
FT /note="H->Y: Loss of HIP2-binding and loss of ubiquitin
FT ligase activity on histone H2A."
FT /evidence="ECO:0000269|PubMed:11513855,
FT ECO:0000269|PubMed:15386022"
FT MUTAGEN 70
FT /note="R->C: Loss of ubiquitin ligase activity on histone
FT H2A."
FT /evidence="ECO:0000269|PubMed:15386022"
FT MUTAGEN 81
FT /note="R->A: Decreases ubiquitin ligase activity on histone
FT H2A."
FT /evidence="ECO:0000269|PubMed:25355358"
FT MUTAGEN 93
FT /note="K->A: Mildly decreases ubiquitin ligase activity on
FT histone H2A."
FT /evidence="ECO:0000269|PubMed:25355358"
FT MUTAGEN 97..98
FT /note="KR->AA: Loss of ubiquitin ligase activity on histone
FT H2A."
FT /evidence="ECO:0000269|PubMed:21772249"
FT MUTAGEN 97
FT /note="K->A: Strongly decreases ubiquitin ligase activity
FT on histone H2A."
FT /evidence="ECO:0000269|PubMed:25355358"
FT MUTAGEN 98
FT /note="R->A: Nearly abolishes ubiquitin ligase activity on
FT histone H2A."
FT /evidence="ECO:0000269|PubMed:25355358"
FT MUTAGEN 168
FT /note="S->E: Decreases ubiquitin ligase activity on histone
FT H2A."
FT /evidence="ECO:0000269|PubMed:25519132"
FT MUTAGEN 247
FT /note="Y->A: Reduced interaction with CBX7."
FT /evidence="ECO:0000269|PubMed:20696397"
FT MUTAGEN 258
FT /note="H->A: Reduced interaction with CBX7."
FT /evidence="ECO:0000269|PubMed:20696397"
FT MUTAGEN 262
FT /note="Y->A: Reduced interaction with CBX7."
FT /evidence="ECO:0000269|PubMed:19791798,
FT ECO:0000269|PubMed:20696397"
FT HELIX 13..16
FT /evidence="ECO:0007829|PDB:6WI7"
FT HELIX 21..25
FT /evidence="ECO:0007829|PDB:6WI7"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:6WI7"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:4S3O"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:6WI7"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:6WI7"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:8GRM"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:6WI7"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:6WI7"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:6WI7"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:6WI7"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:6WI7"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:6WI7"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:6WI7"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:6WI7"
FT HELIX 104..113
FT /evidence="ECO:0007829|PDB:6WI7"
FT STRAND 225..232
FT /evidence="ECO:0007829|PDB:3GS2"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:3GS2"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:3GS2"
FT HELIX 256..277
FT /evidence="ECO:0007829|PDB:3GS2"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:3IXS"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:3IXS"
FT STRAND 291..296
FT /evidence="ECO:0007829|PDB:3GS2"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:3GS2"
FT HELIX 311..318
FT /evidence="ECO:0007829|PDB:3GS2"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:3GS2"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:3GS2"
SQ SEQUENCE 336 AA; 37655 MW; 90EA546E1F4DB7EC CRC64;
MSQAVQTNGT QPLSKTWELS LYELQRTPQE AITDGLEIVV SPRSLHSELM CPICLDMLKN
TMTTKECLHR FCADCIITAL RSGNKECPTC RKKLVSKRSL RPDPNFDALI SKIYPSRDEY
EAHQERVLAR INKHNNQQAL SHSIEEGLKI QAMNRLQRGK KQQIENGSGA EDNGDSSHCS
NASTHSNQEA GPSNKRTKTS DDSGLELDNN NAAMAIDPVM DGASEIELVF RPHPTLMEKD
DSAQTRYIKT SGNATVDHLS KYLAVRLALE ELRSKGESNQ MNLDTASEKQ YTIYIATASG
QFTVLNGSFS LELVSEKYWK VNKPMELYYA PTKEHK
//
