HIC1_HUMAN
ID HIC1_HUMAN Reviewed; 733 AA.
AC Q14526; D3DTI4;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 5.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Hypermethylated in cancer 1 protein;
DE Short=Hic-1;
DE AltName: Full=Zinc finger and BTB domain-containing protein 29;
GN Name=HIC1; Synonyms=ZBTB29;
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 [GENOMIC DNA] (ISOFORM 2), AND VARIANT GLY-725.
RX PubMed=7585125; DOI=10.1038/nm0695-570;
RA Wales M.M., Biel M.A., el Deiry W., Nelkin B.D., Issa J.-P., Cavenee W.K.,
RA Kuerbitz S.J., Baylin S.B.;
RT "p53 activates expression of HIC-1, a new candidate tumour suppressor gene
RT on 17p13.3.";
RL Nat. Med. 1:570-577(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SELF-ASSOCIATION.
RX PubMed=10611298; DOI=10.1073/pnas.96.26.14831;
RA Deltour S., Guerardel C., Leprince D.;
RT "Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a
RT general mechanism for BTB/POZ transcriptional repressors: the case of HIC-1
RT and gammaFBP-B.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14831-14836(1999).
RN [5]
RP ALTERNATIVE SPLICING, INTERACTION WITH HIC2, AND SUBCELLULAR LOCATION.
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 [6]
RP FUNCTION, SELF-ASSOCIATION, AND INTERACTION WITH CTBP1.
RX PubMed=12052894; DOI=10.1128/mcb.22.13.4890-4901.2002;
RA Deltour S., Pinte S., Guerardel C., Wasylyk B., Leprince D.;
RT "The human candidate tumor suppressor gene HIC1 recruits CtBP through a
RT degenerate GLDLSKK motif.";
RL Mol. Cell. Biol. 22:4890-4901(2002).
RN [7]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF CYS-540.
RX PubMed=15231840; DOI=10.1074/jbc.m401610200;
RA Pinte S., Stankovic-Valentin N., Deltour S., Rood B.R., Guerardel C.,
RA Leprince D.;
RT "The tumor suppressor gene HIC1 (hypermethylated in cancer 1) is a
RT sequence-specific transcriptional repressor: definition of its consensus
RT binding sequence and analysis of its DNA binding and repressive
RT properties.";
RL J. Biol. Chem. 279:38313-38324(2004).
RN [8]
RP FUNCTION.
RX PubMed=16269335; DOI=10.1016/j.cell.2005.08.011;
RA Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.;
RT "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent
RT DNA-damage responses.";
RL Cell 123:437-448(2005).
RN [9]
RP FUNCTION.
RX PubMed=16690027; DOI=10.1016/j.bbrc.2006.04.052;
RA Briones V.R., Chen S., Riegel A.T., Lechleider R.J.;
RT "Mechanism of fibroblast growth factor-binding protein 1 repression by TGF-
RT beta.";
RL Biochem. Biophys. Res. Commun. 345:595-601(2006).
RN [10]
RP FUNCTION IN WNT SIGNALING, AND INTERACTION WITH TCF7L2.
RX PubMed=16724116; DOI=10.1038/sj.emboj.7601147;
RA Valenta T., Lukas J., Doubravska L., Fafilek B., Korinek V.;
RT "HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta-catenin to
RT the nuclear bodies.";
RL EMBO J. 25:2326-2337(2006).
RN [11]
RP INTERACTION WITH CTBP1 AND CTBP2, AND MUTAGENESIS OF LEU-244.
RX PubMed=16762039; DOI=10.1111/j.1742-4658.2006.05301.x;
RA Stankovic-Valentin N., Verger A., Deltour-Balerdi S., Quinlan K.G.,
RA Crossley M., Leprince D.;
RT "A L225A substitution in the human tumour suppressor HIC1 abolishes its
RT interaction with the corepressor CtBP.";
RL FEBS J. 273:2879-2890(2006).
RN [12]
RP SUMOYLATION AT LYS-333, ACETYLATION AT LYS-333, AND MUTAGENESIS OF LYS-333;
RP GLU-335 AND PRO-336.
RX PubMed=17283066; DOI=10.1128/mcb.01098-06;
RA Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G.,
RA Guerardel C., Dejean A., Leprince D.;
RT "An acetylation/deacetylation-SUMOylation switch through a phylogenetically
RT conserved psiKXEP motif in the tumor suppressor HIC1 regulates
RT transcriptional repression activity.";
RL Mol. Cell. Biol. 27:2661-2675(2007).
RN [13]
RP RETRACTED PAPER.
RX PubMed=17213307; DOI=10.1073/pnas.0610590104;
RA Zhang Q., Wang S.Y., Fleuriel C., Leprince D., Rocheleau J.V., Piston D.W.,
RA Goodman R.H.;
RT "Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor
RT complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:829-833(2007).
RN [14]
RP RETRACTION NOTICE OF PUBMED:17213307.
RX PubMed=25646486; DOI=10.1073/pnas.1501052112;
RA Zhang Q., Wang S.Y., Fleuriel C., Dominique L., Rocheleau J.V.,
RA Piston D.W., Goodman R.H.;
RL Proc. Natl. Acad. Sci. U.S.A. 112:E819-E819(2015).
RN [15]
RP FUNCTION.
RX PubMed=18347096; DOI=10.1101/gad.1640908;
RA Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T., Devereux W.L.,
RA Baylin S.B., Eberhart C.G., Watkins D.N.;
RT "Cooperation between the Hic1 and Ptch1 tumor suppressors in
RT medulloblastoma.";
RL Genes Dev. 22:770-785(2008).
RN [16]
RP ERRATUM OF PUBMED:18347096.
RA Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T., Devereux W.L.,
RA Baylin S.B., Eberhart C.G., Watkins D.N.;
RL Genes Dev. 22:1410-1410(2008).
RN [17]
RP FUNCTION, AND INTERACTION WITH ARID1A.
RX PubMed=19486893; DOI=10.1016/j.bbrc.2009.05.115;
RA Van Rechem C., Boulay G., Leprince D.;
RT "HIC1 interacts with a specific subunit of SWI/SNF complexes,
RT ARID1A/BAF250A.";
RL Biochem. Biophys. Res. Commun. 385:586-590(2009).
RN [18]
RP FUNCTION.
RX PubMed=19525223; DOI=10.1074/jbc.m109.022350;
RA Van Rechem C., Rood B.R., Touka M., Pinte S., Jenal M., Guerardel C.,
RA Ramsey K., Monte D., Begue A., Tschan M.P., Stephan D.A., Leprince D.;
RT "Scavenger chemokine (CXC motif) receptor 7 (CXCR7) is a direct target gene
RT of HIC1 (hypermethylated in cancer 1).";
RL J. Biol. Chem. 284:20927-20935(2009).
RN [19]
RP FUNCTION, INTERACTION WITH MTA1 AND MBD3, AND MUTAGENESIS OF LYS-333;
RP GLU-335 AND PRO-336.
RX PubMed=20547755; DOI=10.1128/mcb.00582-09;
RA Van Rechem C., Boulay G., Pinte S., Stankovic-Valentin N., Guerardel C.,
RA Leprince D.;
RT "Differential regulation of HIC1 target genes by CtBP and NuRD, via an
RT acetylation/SUMOylation switch, in quiescent versus proliferating cells.";
RL Mol. Cell. Biol. 30:4045-4059(2010).
RN [20]
RP FUNCTION.
RX PubMed=20154726; DOI=10.1038/onc.2010.12;
RA Zhang W., Zeng X., Briggs K.J., Beaty R., Simons B., Chiu Yen R.W.,
RA Tyler M.A., Tsai H.C., Ye Y., Gesell G.S., Herman J.G., Baylin S.B.,
RA Watkins D.N.;
RT "A potential tumor suppressor role for Hic1 in breast cancer through
RT transcriptional repression of ephrin-A1.";
RL Oncogene 29:2467-2476(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237; SER-248 AND SER-366, 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).
CC -!- FUNCTION: Transcriptional repressor (PubMed:12052894, PubMed:15231840).
CC Recognizes and binds to the consensus sequence '5-
CC [CG]NG[CG]GGGCA[CA]CC-3' (PubMed:15231840). May act as a tumor
CC suppressor (PubMed:20154726). Involved in development of head, face,
CC limbs and ventral body wall (By similarity). Involved in down-
CC regulation of SIRT1 and thereby is involved in regulation of p53/TP53-
CC dependent apoptotic DNA-damage responses (PubMed:16269335). The
CC specific target gene promoter association seems to be depend on
CC corepressors, such as CTBP1 or CTBP2 and MTA1 (PubMed:12052894,
CC PubMed:20547755). In cooperation with MTA1 (indicative for an
CC association with the NuRD complex) represses transcription from
CC CCND1/cyclin-D1 and CDKN1C/p57Kip2 specifically in quiescent cells
CC (PubMed:20547755). Involved in regulation of the Wnt signaling pathway
CC probably by association with TCF7L2 and preventing TCF7L2 and CTNNB1
CC association with promoters of TCF-responsive genes (PubMed:16724116).
CC Seems to repress transcription from E2F1 and ATOH1 which involves
CC ARID1A, indicative for the participation of a distinct SWI/SNF-type
CC chromatin-remodeling complex (PubMed:18347096, PubMed:19486893).
CC Probably represses transcription of ACKR3, FGFBP1 and EFNA1
CC (PubMed:16690027, PubMed:19525223, PubMed:20154726).
CC {ECO:0000250|UniProtKB:Q9R1Y5, ECO:0000269|PubMed:12052894,
CC ECO:0000269|PubMed:15231840, ECO:0000269|PubMed:16269335,
CC ECO:0000269|PubMed:16690027, ECO:0000269|PubMed:16724116,
CC ECO:0000269|PubMed:18347096, ECO:0000269|PubMed:19486893,
CC ECO:0000269|PubMed:19525223, ECO:0000269|PubMed:20154726,
CC ECO:0000269|PubMed:20547755}.
CC -!- SUBUNIT: Self-associates (PubMed:10611298, PubMed:12052894). Interacts
CC with HIC2 (PubMed:11554746). Interacts with CTBP1 and CTBP2
CC (PubMed:12052894, PubMed:16762039). Interacts with TCF7L2 and ARID1A
CC (PubMed:16724116, PubMed:19486893). Interacts with MTA1 and MBD3;
CC indicative for an association with the NuRD complex (PubMed:20547755).
CC Interacts with SIRT1 (By similarity). {ECO:0000250|UniProtKB:Q9R1Y5,
CC ECO:0000269|PubMed:10611298, ECO:0000269|PubMed:11554746,
CC ECO:0000269|PubMed:12052894, ECO:0000269|PubMed:16724116,
CC ECO:0000269|PubMed:16762039, ECO:0000269|PubMed:19486893,
CC ECO:0000269|PubMed:20547755}.
CC -!- INTERACTION:
CC Q14526; O14497: ARID1A; NbExp=2; IntAct=EBI-2507362, EBI-637887;
CC Q14526; Q13363: CTBP1; NbExp=2; IntAct=EBI-2507362, EBI-908846;
CC Q14526; P56545: CTBP2; NbExp=2; IntAct=EBI-2507362, EBI-741533;
CC Q14526; Q9NQB0: TCF7L2; NbExp=6; IntAct=EBI-2507362, EBI-924724;
CC Q14526; O88712: Ctbp1; Xeno; NbExp=10; IntAct=EBI-2507362, EBI-604547;
CC Q14526; P56546: Ctbp2; Xeno; NbExp=2; IntAct=EBI-2507362, EBI-1384883;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11554746}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q14526-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14526-2; Sequence=VSP_006826;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels found in
CC lung, colon, prostate, thymus, testis and ovary. Expression is absent
CC or decreased in many tumor cells.
CC -!- DOMAIN: The BTB domain inhibits the binding to a single consensus
CC binding site, but mediates cooperative binding to multiple binding
CC sites.
CC -!- PTM: Acetylated on several residues, including Lys-333. Lys-333 is
CC deacetylated by SIRT1. {ECO:0000269|PubMed:17283066}.
CC -!- PTM: Sumoylated on Lys-333 by a PIAS family member, which enhances
CC interaction with MTA1, positively regulates transcriptional repression
CC activity and is enhanced by HDAC4. {ECO:0000269|PubMed:17283066}.
CC -!- MISCELLANEOUS: The HIC1 gene is frequently found epigenetically
CC silenced or deleted in different types of solid tumors.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. Hic subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HIC1ID40819ch17p13.html";
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DR EMBL; L41919; AAD09201.1; -; Genomic_DNA.
DR EMBL; AC090617; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90562.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90563.1; -; Genomic_DNA.
DR CCDS; CCDS42229.1; -. [Q14526-1]
DR CCDS; CCDS42230.1; -. [Q14526-2]
DR RefSeq; NP_001091672.1; NM_001098202.1. [Q14526-1]
DR RefSeq; NP_006488.2; NM_006497.3. [Q14526-2]
DR AlphaFoldDB; Q14526; -.
DR SMR; Q14526; -.
DR BioGRID; 109337; 38.
DR CORUM; Q14526; -.
DR ELM; Q14526; -.
DR IntAct; Q14526; 12.
DR MINT; Q14526; -.
DR STRING; 9606.ENSP00000314080; -.
DR GlyGen; Q14526; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14526; -.
DR PhosphoSitePlus; Q14526; -.
DR BioMuta; HIC1; -.
DR DMDM; 296439502; -.
DR jPOST; Q14526; -.
DR MassIVE; Q14526; -.
DR PaxDb; Q14526; -.
DR PeptideAtlas; Q14526; -.
DR PRIDE; Q14526; -.
DR ProteomicsDB; 60028; -. [Q14526-1]
DR ProteomicsDB; 60029; -. [Q14526-2]
DR TopDownProteomics; Q14526-1; -. [Q14526-1]
DR Antibodypedia; 5361; 289 antibodies from 32 providers.
DR DNASU; 3090; -.
DR Ensembl; ENST00000322941.3; ENSP00000314080.3; ENSG00000177374.13. [Q14526-1]
DR Ensembl; ENST00000399849.4; ENSP00000382742.2; ENSG00000177374.13. [Q14526-2]
DR Ensembl; ENST00000619757.5; ENSP00000477858.1; ENSG00000177374.13. [Q14526-2]
DR GeneID; 3090; -.
DR KEGG; hsa:3090; -.
DR MANE-Select; ENST00000619757.5; ENSP00000477858.1; NM_006497.4; NP_006488.2. [Q14526-2]
DR UCSC; uc002fty.5; human. [Q14526-1]
DR CTD; 3090; -.
DR DisGeNET; 3090; -.
DR GeneCards; HIC1; -.
DR HGNC; HGNC:4909; HIC1.
DR HPA; ENSG00000177374; Low tissue specificity.
DR MalaCards; HIC1; -.
DR MIM; 603825; gene.
DR neXtProt; NX_Q14526; -.
DR OpenTargets; ENSG00000177374; -.
DR Orphanet; 531; Miller-Dieker syndrome.
DR PharmGKB; PA29282; -.
DR VEuPathDB; HostDB:ENSG00000177374; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000161725; -.
DR HOGENOM; CLU_015352_1_0_1; -.
DR InParanoid; Q14526; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q14526; -.
DR TreeFam; TF333488; -.
DR PathwayCommons; Q14526; -.
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors.
DR SignaLink; Q14526; -.
DR SIGNOR; Q14526; -.
DR BioGRID-ORCS; 3090; 7 hits in 1125 CRISPR screens.
DR ChiTaRS; HIC1; human.
DR GeneWiki; HIC1; -.
DR GenomeRNAi; 3090; -.
DR Pharos; Q14526; Tbio.
DR PRO; PR:Q14526; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14526; protein.
DR Bgee; ENSG00000177374; Expressed in cardiac muscle of right atrium and 123 other tissues.
DR ExpressionAtlas; Q14526; baseline and differential.
DR Genevisible; Q14526; HS.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR028424; HIC1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR24390:SF145; PTHR24390:SF145; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF00096; zf-C2H2; 4.
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 Acetylation; Alternative splicing; Developmental protein; DNA-binding;
KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..733
FT /note="Hypermethylated in cancer 1 protein"
FT /id="PRO_0000046942"
FT DOMAIN 47..110
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT ZN_FING 439..459
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 509..529
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 537..557
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 565..585
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 593..613
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 154..315
FT /note="Mediates HDAC-dependent transcriptional repression"
FT REGION 189..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..247
FT /note="Interaction with CTBP1"
FT COMPBIAS 189..205
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..290
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..361
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 159
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1Y5"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 333
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:17283066"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 704
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1Y5"
FT CROSSLNK 333
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT VAR_SEQ 1..19
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006826"
FT VARIANT 725
FT /note="R -> G (in dbSNP:rs1063317)"
FT /evidence="ECO:0000269|PubMed:7585125"
FT /id="VAR_063109"
FT MUTAGEN 244
FT /note="L->A: Abolishes interaction with CTBP1 and CTBP2.
FT Impairs transcriptional repression."
FT /evidence="ECO:0000269|PubMed:16762039"
FT MUTAGEN 333
FT /note="K->Q: Mimicks acetylation. Impairs interaction with
FT RBBP4 and MTA1 and no effect on interaction with CTBP2.
FT Reduces transcriptional repression."
FT /evidence="ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755"
FT MUTAGEN 333
FT /note="K->R: Abolishes sumoylation; impairs transcriptional
FT repression activity."
FT /evidence="ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755"
FT MUTAGEN 335
FT /note="E->A: Impairs transcriptional repression activity.
FT Decreases interaction with MTA1."
FT /evidence="ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755"
FT MUTAGEN 336
FT /note="P->A: Impairs K-333 acetylation; no effect on
FT sumoylation. Decreases interaction with MTA1."
FT /evidence="ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755"
FT MUTAGEN 540
FT /note="C->S: Abolishes repression activity."
FT /evidence="ECO:0000269|PubMed:15231840"
FT CONFLICT 190
FT /note="P -> R (in Ref. 1; AAD09201)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 733 AA; 76508 MW; 6DDD0F49C4E490D3 CRC64;
MTFPEADILL KSGECAGQTM LDTMEAPGHS RQLLLQLNNQ RTKGFLCDVI IVVQNALFRA
HKNVLAASSA YLKSLVVHDN LLNLDHDMVS PAVFRLVLDF IYTGRLADGA EAAAAAAVAP
GAEPSLGAVL AAASYLQIPD LVALCKKRLK RHGKYCHLRG GGGGGGGYAP YGRPGRGLRA
ATPVIQACYP SPVGPPPPPA AEPPSGPEAA VNTHCAELYA SGPGPAAALC ASERRCSPLC
GLDLSKKSPP GSAAPERPLA ERELPPRPDS PPSAGPAAYK EPPLALPSLP PLPFQKLEEA
APPSDPFRGG SGSPGPEPPG RPDGPSLLYR WMKHEPGLGS YGDELGRERG SPSERCEERG
GDAAVSPGGP PLGLAPPPRY PGSLDGPGAG GDGDDYKSSS EETGSSEDPS PPGGHLEGYP
CPHLAYGEPE SFGDNLYVCI PCGKGFPSSE QLNAHVEAHV EEEEALYGRA EAAEVAAGAA
GLGPPFGGGG DKVAGAPGGL GELLRPYRCA SCDKSYKDPA TLRQHEKTHW LTRPYPCTIC
GKKFTQRGTM TRHMRSHLGL KPFACDACGM RFTRQYRLTE HMRIHSGEKP YECQVCGGKF
AQQRNLISHM KMHAVGGAAG AAGALAGLGG LPGVPGPDGK GKLDFPEGVF AVARLTAEQL
SLKQQDKAAA AELLAQTTHF LHDPKVALES LYPLAKFTAE LGLSPDKAAE VLSQGAHLAA
GPDGRTIDRF SPT
