HIC2_HUMAN
ID HIC2_HUMAN Reviewed; 615 AA.
AC Q96JB3; Q504T6; Q96KR3; Q9NSM9; Q9UPX9;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Hypermethylated in cancer 2 protein;
DE Short=Hic-2;
DE AltName: Full=HIC1-related gene on chromosome 22 protein;
DE AltName: Full=Hic-3;
DE AltName: Full=Zinc finger and BTB domain-containing protein 30;
GN Name=HIC2; Synonyms=HRG22, KIAA1020, ZBTB30;
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] OF 1-85 (ISOFORM 1), ALTERNATIVE SPLICING,
RP SELF-ASSOCIATION, AND INTERACTION WITH HIC1.
RX PubMed=11554746; DOI=10.1006/bbrc.2001.5624;
RA Deltour S., Pinte S., Guerardel C., Leprince D.;
RT "Characterization of HRG22, a human homologue of the putative tumor
RT suppressor gene HIC1.";
RL Biochem. Biophys. Res. Commun. 287:427-434(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Alliel P.M., Goudou D., Bitoun M., Seddiqi N., Rieger F., Perin J.-P.;
RT "Complete deduced structure of HIC-3, a novel human btb/poz and ZF factor
RT of the HIC family.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 301-615.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; SER-169; SER-197;
RP SER-348 AND SER-412, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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).
CC -!- FUNCTION: Transcriptional repressor.
CC -!- SUBUNIT: Self-associates. Interacts with HIC1.
CC {ECO:0000269|PubMed:11554746}.
CC -!- INTERACTION:
CC Q96JB3; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-726282, EBI-739624;
CC Q96JB3; Q96KQ7: EHMT2; NbExp=3; IntAct=EBI-726282, EBI-744366;
CC Q96JB3; Q96BR9: ZBTB8A; NbExp=5; IntAct=EBI-726282, EBI-742740;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96JB3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96JB3-2; Sequence=VSP_006829;
CC -!- TISSUE SPECIFICITY: Highest levels in cerebellum.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. Hic subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA82972.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ313204; CAC70715.1; -; mRNA.
DR EMBL; AF349035; AAK72951.1; -; mRNA.
DR EMBL; AB028943; BAA82972.2; ALT_INIT; mRNA.
DR EMBL; CR456377; CAG30263.1; -; mRNA.
DR EMBL; AP000557; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC094787; AAH94787.1; -; mRNA.
DR EMBL; AL162003; CAB82344.1; -; mRNA.
DR CCDS; CCDS13789.1; -. [Q96JB3-1]
DR PIR; T47181; T47181.
DR RefSeq; NP_055909.2; NM_015094.2. [Q96JB3-1]
DR RefSeq; XP_011528309.1; XM_011530007.2. [Q96JB3-1]
DR RefSeq; XP_011528310.1; XM_011530008.2. [Q96JB3-1]
DR RefSeq; XP_011528311.1; XM_011530009.2. [Q96JB3-1]
DR RefSeq; XP_011528312.1; XM_011530010.2. [Q96JB3-1]
DR RefSeq; XP_016884158.1; XM_017028669.1. [Q96JB3-2]
DR AlphaFoldDB; Q96JB3; -.
DR SMR; Q96JB3; -.
DR BioGRID; 116741; 50.
DR IntAct; Q96JB3; 27.
DR MINT; Q96JB3; -.
DR STRING; 9606.ENSP00000387757; -.
DR iPTMnet; Q96JB3; -.
DR PhosphoSitePlus; Q96JB3; -.
DR SwissPalm; Q96JB3; -.
DR BioMuta; HIC2; -.
DR DMDM; 20454983; -.
DR EPD; Q96JB3; -.
DR jPOST; Q96JB3; -.
DR MassIVE; Q96JB3; -.
DR MaxQB; Q96JB3; -.
DR PaxDb; Q96JB3; -.
DR PeptideAtlas; Q96JB3; -.
DR PRIDE; Q96JB3; -.
DR ProteomicsDB; 76928; -. [Q96JB3-1]
DR ProteomicsDB; 76929; -. [Q96JB3-2]
DR Antibodypedia; 8461; 246 antibodies from 31 providers.
DR DNASU; 23119; -.
DR Ensembl; ENST00000407464.7; ENSP00000385319.2; ENSG00000169635.10. [Q96JB3-1]
DR Ensembl; ENST00000407598.2; ENSP00000384889.2; ENSG00000169635.10. [Q96JB3-1]
DR Ensembl; ENST00000443632.2; ENSP00000387757.2; ENSG00000169635.10. [Q96JB3-1]
DR GeneID; 23119; -.
DR KEGG; hsa:23119; -.
DR MANE-Select; ENST00000407464.7; ENSP00000385319.2; NM_015094.3; NP_055909.2.
DR UCSC; uc002zur.5; human. [Q96JB3-1]
DR CTD; 23119; -.
DR DisGeNET; 23119; -.
DR GeneCards; HIC2; -.
DR HGNC; HGNC:18595; HIC2.
DR HPA; ENSG00000169635; Low tissue specificity.
DR MIM; 607712; gene.
DR neXtProt; NX_Q96JB3; -.
DR OpenTargets; ENSG00000169635; -.
DR PharmGKB; PA38357; -.
DR VEuPathDB; HostDB:ENSG00000169635; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000159978; -.
DR HOGENOM; CLU_015352_1_0_1; -.
DR InParanoid; Q96JB3; -.
DR OMA; HTPQELP; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q96JB3; -.
DR TreeFam; TF333488; -.
DR PathwayCommons; Q96JB3; -.
DR SignaLink; Q96JB3; -.
DR BioGRID-ORCS; 23119; 21 hits in 1134 CRISPR screens.
DR ChiTaRS; HIC2; human.
DR GeneWiki; HIC2; -.
DR GenomeRNAi; 23119; -.
DR Pharos; Q96JB3; Tbio.
DR PRO; PR:Q96JB3; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q96JB3; protein.
DR Bgee; ENSG00000169635; Expressed in secondary oocyte and 187 other tissues.
DR Genevisible; Q96JB3; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF54695; SSF54695; 1.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..615
FT /note="Hypermethylated in cancer 2 protein"
FT /id="PRO_0000046945"
FT DOMAIN 46..109
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT ZN_FING 442..469
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 505..532
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 533..560
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 561..588
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 589..615
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 144..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..250
FT /note="Binding to CtBP"
FT COMPBIAS 270..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_006829"
FT CONFLICT 49..51
FT /note="IIM -> TIR (in Ref. 1; CAC70715)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="Q -> R (in Ref. 3; BAA82972)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 615 AA; 66156 MW; B0368C631B198C95 CRC64;
MVSGPLALRW CAWAGRGDMG PDMELPSHSK QLLLQLNQQR TKGFLCDVII MVENSIFRAH
KNVLAASSIY FKSLVLHDNL INLDTDMVSS TVFQQILDFI YTGKLLPSDQ PAEPNFSTLL
TAASYLQLPE LAALCRRKLK RAGKPFGSGR AGSTGMGRPP RSQRLSTASV IQARYQGLVD
GRKGAHAPQE LPQAKGSDDE LFLGGSNQDS VQGLGRAVCP AGGEAGLGGC SSSTNGSSGG
CEQELGLDLS KKSPPLPPAT PGPHLTPDDA AQLSDSQHGS PPAASAPPVA NSASYSELGG
TPDEPMDLEG AEDNHLSLLE APGGQPRKSL RHSTRKKEWG KKEPVAGSPF ERREAGPKGP
CPGEEGEGVG DRVPNGILAS GAGPSGPYGE PPYPCKEEEE NGKDASEDSA QSGSEGGSGH
ASAHYMYRQE GYETVSYGDN LYVCIPCAKG FPSSEQLNAH VETHTEEELF IKEEGAYETG
SGGAEEEAED LSAPSAAYTA EPRPFKCSVC EKTYKDPATL RQHEKTHWLT RPFPCNICGK
MFTQRGTMTR HMRSHLGLKP FACDECGMRF TRQYRLTEHM RVHSGEKPYE CQLCGGKFTQ
QRNLISHLRM HTSPS
