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Database: UniProt
Entry: Q9HCK8
LinkDB: Q9HCK8
Original site: Q9HCK8 
ID   CHD8_HUMAN              Reviewed;        2581 AA.
AC   Q9HCK8; Q4G0D8; Q68DQ0; Q6DKH9; Q6P440; Q6ZNL7; Q8N3Z9; Q8NCY4;
AC   Q8TBR9; Q96F26;
DT   19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 5.
DT   16-OCT-2019, entry version 188.
DE   RecName: Full=Chromodomain-helicase-DNA-binding protein 8 {ECO:0000255|HAMAP-Rule:MF_03071};
DE            Short=CHD-8 {ECO:0000255|HAMAP-Rule:MF_03071};
DE            EC=3.6.4.12 {ECO:0000255|HAMAP-Rule:MF_03071};
DE   AltName: Full=ATP-dependent helicase CHD8 {ECO:0000255|HAMAP-Rule:MF_03071};
DE   AltName: Full=Helicase with SNF2 domain 1;
GN   Name=CHD8 {ECO:0000255|HAMAP-Rule:MF_03071};
GN   Synonyms=HELSNF1, KIAA1564;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lymph node, and Uterine endothelium;
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.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA   Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA   Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA   Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA   Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA   Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA   Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA   Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA   Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA   Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA   Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA   Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA   Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA   Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA   Quetier F., Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-176 (ISOFORM 1).
RG   The Cancer Genome Anatomy Project (CGAP) at the National Cancer Institute;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 150-2581 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA   Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes.
RT   XVIII. The complete sequences of 100 new cDNA clones from brain which
RT   code for large proteins in vitro.";
RL   DNA Res. 7:273-281(2000).
RN   [5]
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   [6]
RP   SEQUENCE REVISION.
RA   Ohara O., Nagase T., Kikuno R.;
RL   Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1038-2581.
RC   TISSUE=Spleen;
RA   Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.;
RT   "The nucleotide sequence of a long cDNA clone isolated from human
RT   spleen.";
RL   Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1674-2581.
RC   TISSUE=Brain, Duodenum, Liver, Lung, and Spleen;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
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   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [11]
RP   INTERACTION WITH CTCF.
RX   PubMed=16949368; DOI=10.1016/j.molcel.2006.08.008;
RA   Ishihara K., Oshimura M., Nakao M.;
RT   "CTCF-dependent chromatin insulator is linked to epigenetic
RT   remodeling.";
RL   Mol. Cell 23:733-742(2006).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2051, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein
RT   phosphorylation analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [13]
RP   FUNCTION, AND INTERACTION WITH ZNF143.
RX   PubMed=17938208; DOI=10.1128/mcb.00846-07;
RA   Yuan C.-C., Zhao X., Florens L., Swanson S.K., Washburn M.P.,
RA   Hernandez N.;
RT   "CHD8 associates with human Staf and contributes to efficient U6 RNA
RT   polymerase III transcription.";
RL   Mol. Cell. Biol. 27:8729-8738(2007).
RN   [14]
RP   POSSIBLE ASSOCIATION WITH DEVELOPMENTAL DELAY.
RX   PubMed=17545556; DOI=10.1136/jmg.2007.050823;
RA   Zahir F., Firth H.V., Baross A., Delaney A.D., Eydoux P., Gibson W.T.,
RA   Langlois S., Martin H., Willatt L., Marra M.A., Friedman J.M.;
RT   "Novel deletions of 14q11.2 associated with developmental delay,
RT   cognitive impairment and similar minor anomalies in three children.";
RL   J. Med. Genet. 44:556-561(2007).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2182 AND SER-2211, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA   Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT   efficient phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [16]
RP   FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH CTNNB1,
RP   IDENTIFICATION IN A COMPLEX WITH WDR5, AND MUTAGENESIS OF LYS-842.
RX   PubMed=18378692; DOI=10.1128/mcb.00322-08;
RA   Thompson B.A., Tremblay V., Lin G., Bochar D.A.;
RT   "CHD8 is an ATP-dependent chromatin remodeling factor that regulates
RT   beta-catenin target genes.";
RL   Mol. Cell. Biol. 28:3894-3904(2008).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562; SER-1976; SER-2008;
RP   SER-2046 AND SER-2519, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP   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   [18]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; SER-1420; SER-1424;
RP   THR-1993; SER-2008 AND SER-2200, AND IDENTIFICATION BY MASS
RP   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   [20]
RP   INTERACTION WITH CHD7, AND SUBCELLULAR LOCATION.
RX   PubMed=20453063; DOI=10.1093/hmg/ddq189;
RA   Batsukh T., Pieper L., Koszucka A.M., von Velsen N., Hoyer-Fender S.,
RA   Elbracht M., Bergman J.E., Hoefsloot L.H., Pauli S.;
RT   "CHD8 interacts with CHD7, a protein which is mutated in CHARGE
RT   syndrome.";
RL   Hum. Mol. Genet. 19:2858-2866(2010).
RN   [21]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1420; SER-1424; SER-2008
RP   AND SER-2046, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [22]
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.,
RA   Buerckstuemmer T., 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   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1420; SER-1424;
RP   SER-2046; SER-2069 AND SER-2071, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [24]
RP   INTERACTION WITH FAM124B.
RX   PubMed=23285124; DOI=10.1371/journal.pone.0052640;
RA   Batsukh T., Schulz Y., Wolf S., Rabe T.I., Oellerich T., Urlaub H.,
RA   Schaefer I.M., Pauli S.;
RT   "Identification and characterization of FAM124B as a novel component
RT   of a CHD7 and CHD8 containing complex.";
RL   PLoS ONE 7:E52640-E52640(2012).
RN   [25]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432; SER-1978; SER-2046
RP   AND SER-2519, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   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   [26]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2256, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25218447; DOI=10.1038/nsmb.2890;
RA   Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA   Vertegaal A.C.;
RT   "Uncovering global SUMOylation signaling networks in a site-specific
RT   manner.";
RL   Nat. Struct. Mol. Biol. 21:927-936(2014).
RN   [27]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2025, AND IDENTIFICATION BY
RP   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-
RT   modification with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
RN   [28]
RP   STRUCTURE BY NMR OF 2291-2372.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the first BRK domain from human chromodomain-
RT   helicase-DNA-binding protein 8.";
RL   Submitted (OCT-2006) to the PDB data bank.
RN   [29]
RP   VARIANT AUTS18 HIS-2498 DEL.
RX   PubMed=23160955; DOI=10.1126/science.1227764;
RA   O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B.,
RA   Phelps I.G., Carvill G., Kumar A., Lee C., Ankenman K., Munson J.,
RA   Hiatt J.B., Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P.,
RA   Martin B.K., Borenstein E., Nickerson D.A., Mefford H.C., Doherty D.,
RA   Akey J.M., Bernier R., Eichler E.E., Shendure J.;
RT   "Multiplex targeted sequencing identifies recurrently mutated genes in
RT   autism spectrum disorders.";
RL   Science 338:1619-1622(2012).
RN   [30]
RP   VARIANT AUTS18 ILE-744.
RX   PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA   D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA   Sestan N., Walsh C.A.;
RT   "Targeted DNA Sequencing from Autism Spectrum Disorder Brains
RT   Implicates Multiple Genetic Mechanisms.";
RL   Neuron 88:910-917(2015).
CC   -!- FUNCTION: DNA helicase that acts as a chromatin remodeling factor
CC       and regulates transcription. Acts as a transcription repressor by
CC       remodeling chromatin structure and recruiting histone H1 to target
CC       genes. Suppresses p53/TP53-mediated apoptosis by recruiting
CC       histone H1 and preventing p53/TP53 transactivation activity. Acts
CC       as a negative regulator of Wnt signaling pathway by regulating
CC       beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-
CC       targeted gene expression by being recruited specifically to the
CC       promoter regions of several CTNNB1 responsive genes. Involved in
CC       both enhancer blocking and epigenetic remodeling at chromatin
CC       boundary via its interaction with CTCF. Acts as a suppressor of
CC       STAT3 activity by suppressing the LIF-induced STAT3
CC       transcriptional activity. Also acts as a transcription activator
CC       via its interaction with ZNF143 by participating in efficient U6
CC       RNA polymerase III transcription. {ECO:0000255|HAMAP-
CC       Rule:MF_03071, ECO:0000269|PubMed:17938208,
CC       ECO:0000269|PubMed:18378692}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03071};
CC   -!- SUBUNIT: Interacts with p53/TP53, histone H1, CTNNB1, CTCF and
CC       PIAS3. Component of some MLL1/MLL complex, at least composed of
CC       the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5,
CC       as well as the facultative components BAP18, CHD8, E2F6, HSP70,
CC       INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20,
CC       PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6,
CC       TAF7, TAF9 and TEX10. Interacts with CHD7. Interacts with FAM124B
CC       (PubMed:23285124). {ECO:0000255|HAMAP-Rule:MF_03071,
CC       ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:16949368,
CC       ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692,
CC       ECO:0000269|PubMed:20453063, ECO:0000269|PubMed:23285124}.
CC   -!- INTERACTION:
CC       Q9UBL3:ASH2L; NbExp=2; IntAct=EBI-1169146, EBI-540797;
CC       Q9P2D1:CHD7; NbExp=3; IntAct=EBI-4410319, EBI-3951683;
CC       Q15291:RBBP5; NbExp=2; IntAct=EBI-1169146, EBI-592823;
CC       P61964:WDR5; NbExp=3; IntAct=EBI-1169146, EBI-540834;
CC       O95365:ZBTB7A; NbExp=2; IntAct=EBI-1169146, EBI-2795384;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03071,
CC       ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:20453063}.
CC       Note=Localizes to the promoter regions of several CTNNB1-
CC       responsive genes. Also present at known CTCF target sites.
CC       {ECO:0000255|HAMAP-Rule:MF_03071}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9HCK8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9HCK8-2; Sequence=VSP_017270;
CC         Note=No experimental confirmation available.;
CC   -!- PTM: Sumoylated. {ECO:0000255|HAMAP-Rule:MF_03071}.
CC   -!- DISEASE: Autism 18 (AUTS18) [MIM:615032]: A complex
CC       multifactorial, pervasive developmental disorder characterized by
CC       impairments in reciprocal social interaction and communication,
CC       restricted and stereotyped patterns of interests and activities,
CC       and the presence of developmental abnormalities by 3 years of age.
CC       Most individuals with autism also manifest moderate mental
CC       retardation. {ECO:0000269|PubMed:23160955,
CC       ECO:0000269|PubMed:26637798}. Note=Disease susceptibility is
CC       associated with variations affecting the gene represented in this
CC       entry.
CC   -!- MISCELLANEOUS: Its gene is located in the 14q11.2 region of the
CC       genome which is associated with developmental delay, cognitive
CC       impairment and similar minor anomalies in some children,
CC       suggesting that it may be a good candidate for the phenotype.
CC   -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. CHD8
CC       subfamily. {ECO:0000255|HAMAP-Rule:MF_03071}.
DR   EMBL; CR749315; CAH18170.1; -; mRNA.
DR   EMBL; AL834524; CAD39180.1; -; mRNA.
DR   EMBL; AL135744; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL161747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CB043942; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AB046784; BAB13390.3; -; mRNA.
DR   EMBL; AK131077; BAC85127.1; -; mRNA.
DR   EMBL; BC011695; AAH11695.2; -; mRNA.
DR   EMBL; BC025964; AAH25964.1; -; mRNA.
DR   EMBL; BC036920; AAH36920.1; -; mRNA.
DR   EMBL; BC063693; AAH63693.1; -; mRNA.
DR   EMBL; BC073903; AAH73903.1; -; mRNA.
DR   EMBL; BC098452; AAH98452.1; -; mRNA.
DR   CCDS; CCDS45081.1; -. [Q9HCK8-2]
DR   CCDS; CCDS53885.1; -. [Q9HCK8-1]
DR   RefSeq; NP_001164100.1; NM_001170629.1. [Q9HCK8-1]
DR   RefSeq; NP_065971.2; NM_020920.3. [Q9HCK8-2]
DR   PDB; 2CKA; NMR; -; A=2291-2364.
DR   PDB; 2DL6; NMR; -; A=2303-2372.
DR   PDBsum; 2CKA; -.
DR   PDBsum; 2DL6; -.
DR   SMR; Q9HCK8; -.
DR   BioGrid; 121709; 83.
DR   CORUM; Q9HCK8; -.
DR   DIP; DIP-38021N; -.
DR   ELM; Q9HCK8; -.
DR   IntAct; Q9HCK8; 56.
DR   MINT; Q9HCK8; -.
DR   STRING; 9606.ENSP00000382863; -.
DR   iPTMnet; Q9HCK8; -.
DR   PhosphoSitePlus; Q9HCK8; -.
DR   BioMuta; CHD8; -.
DR   DMDM; 317373586; -.
DR   EPD; Q9HCK8; -.
DR   jPOST; Q9HCK8; -.
DR   MassIVE; Q9HCK8; -.
DR   MaxQB; Q9HCK8; -.
DR   PaxDb; Q9HCK8; -.
DR   PeptideAtlas; Q9HCK8; -.
DR   PRIDE; Q9HCK8; -.
DR   ProteomicsDB; 81748; -. [Q9HCK8-1]
DR   ProteomicsDB; 81749; -. [Q9HCK8-2]
DR   Ensembl; ENST00000399982; ENSP00000382863; ENSG00000100888. [Q9HCK8-1]
DR   Ensembl; ENST00000430710; ENSP00000406288; ENSG00000100888. [Q9HCK8-2]
DR   Ensembl; ENST00000557364; ENSP00000451601; ENSG00000100888. [Q9HCK8-1]
DR   Ensembl; ENST00000643469; ENSP00000495070; ENSG00000100888. [Q9HCK8-1]
DR   Ensembl; ENST00000645929; ENSP00000494402; ENSG00000100888. [Q9HCK8-2]
DR   Ensembl; ENST00000646647; ENSP00000495240; ENSG00000100888. [Q9HCK8-1]
DR   GeneID; 57680; -.
DR   KEGG; hsa:57680; -.
DR   UCSC; uc001war.3; human. [Q9HCK8-1]
DR   CTD; 57680; -.
DR   DisGeNET; 57680; -.
DR   GeneCards; CHD8; -.
DR   HGNC; HGNC:20153; CHD8.
DR   HPA; HPA052186; -.
DR   MalaCards; CHD8; -.
DR   MIM; 610528; gene.
DR   MIM; 615032; phenotype.
DR   neXtProt; NX_Q9HCK8; -.
DR   OpenTargets; ENSG00000100888; -.
DR   Orphanet; 106; NON RARE IN EUROPE: Autism.
DR   PharmGKB; PA134957052; -.
DR   eggNOG; KOG0383; Eukaryota.
DR   eggNOG; COG0553; LUCA.
DR   GeneTree; ENSGT00940000153649; -.
DR   InParanoid; Q9HCK8; -.
DR   KO; K04494; -.
DR   OMA; RITKAPG; -.
DR   OrthoDB; 7181at2759; -.
DR   PhylomeDB; Q9HCK8; -.
DR   TreeFam; TF313572; -.
DR   Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR   SIGNOR; Q9HCK8; -.
DR   ChiTaRS; CHD8; human.
DR   EvolutionaryTrace; Q9HCK8; -.
DR   GeneWiki; CHD8; -.
DR   GenomeRNAi; 57680; -.
DR   Pharos; Q9HCK8; -.
DR   PRO; PR:Q9HCK8; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   Bgee; ENSG00000100888; Expressed in 225 organ(s), highest expression level in cerebellar hemisphere.
DR   ExpressionAtlas; Q9HCK8; baseline and differential.
DR   Genevisible; Q9HCK8; HS.
DR   GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0070016; F:armadillo repeat domain binding; IEA:Ensembl.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0008013; F:beta-catenin binding; IDA:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR   GO; GO:0003678; F:DNA helicase activity; IMP:UniProtKB.
DR   GO; GO:0008094; F:DNA-dependent ATPase activity; IDA:UniProtKB.
DR   GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR   GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR   GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR   GO; GO:0043044; P:ATP-dependent chromatin remodeling; IMP:UniProtKB.
DR   GO; GO:0007420; P:brain development; IMP:GO_Central.
DR   GO; GO:0048565; P:digestive tract development; IMP:GO_Central.
DR   GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR   GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:GO_Central.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IMP:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0060134; P:prepulse inhibition; IEA:Ensembl.
DR   GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   Gene3D; 2.20.28.130; -; 1.
DR   Gene3D; 3.40.50.10810; -; 1.
DR   HAMAP; MF_03071; CHD8; 1.
DR   InterPro; IPR006576; BRK_domain.
DR   InterPro; IPR037259; BRK_sf.
DR   InterPro; IPR034724; CHD8.
DR   InterPro; IPR016197; Chromo-like_dom_sf.
DR   InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR   InterPro; IPR023780; Chromo_domain.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR038718; SNF2-like_sf.
DR   InterPro; IPR000330; SNF2_N.
DR   Pfam; PF07533; BRK; 1.
DR   Pfam; PF00385; Chromo; 2.
DR   Pfam; PF00271; Helicase_C; 1.
DR   Pfam; PF00176; SNF2_N; 1.
DR   SMART; SM00592; BRK; 2.
DR   SMART; SM00298; CHROMO; 2.
DR   SMART; SM00487; DEXDc; 1.
DR   SMART; SM00490; HELICc; 1.
DR   SUPFAM; SSF160481; SSF160481; 1.
DR   SUPFAM; SSF52540; SSF52540; 2.
DR   SUPFAM; SSF54160; SSF54160; 2.
DR   PROSITE; PS50013; CHROMO_2; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Alternative splicing; ATP-binding; Autism;
KW   Autism spectrum disorder; Chromatin regulator; Complete proteome;
KW   Disease mutation; DNA-binding; Helicase; Hydrolase; Isopeptide bond;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Repeat; Repressor; Transcription; Transcription regulation;
KW   Ubl conjugation; Wnt signaling pathway.
FT   CHAIN         1   2581       Chromodomain-helicase-DNA-binding protein
FT                                8.
FT                                /FTId=PRO_0000080233.
FT   DOMAIN      642    709       Chromo 1. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   DOMAIN      724    790       Chromo 2. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   DOMAIN      823    997       Helicase ATP-binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   DOMAIN     1137   1288       Helicase C-terminal. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   NP_BIND     836    843       ATP. {ECO:0000255|HAMAP-Rule:MF_03071}.
FT   REGION     1789   2302       Interaction with FAM124B.
FT                                {ECO:0000255|HAMAP-Rule:MF_03071,
FT                                ECO:0000269|PubMed:23285124}.
FT   MOTIF       948    951       DEAH box. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   COMPBIAS    292    410       Gln-rich. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   COMPBIAS   2069   2098       Ser-rich. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   COMPBIAS   2493   2508       His-rich. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   COMPBIAS   2539   2581       Asp-rich. {ECO:0000255|HAMAP-
FT                                Rule:MF_03071}.
FT   MOD_RES     432    432       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     553    553       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332}.
FT   MOD_RES     562    562       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES    1420   1420       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692}.
FT   MOD_RES    1424   1424       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692}.
FT   MOD_RES    1976   1976       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES    1978   1978       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1993   1993       Phosphothreonine.
FT                                {ECO:0000244|PubMed:19690332}.
FT   MOD_RES    1995   1995       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9JIX5}.
FT   MOD_RES    2008   2008       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231}.
FT   MOD_RES    2046   2046       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES    2051   2051       Phosphothreonine.
FT                                {ECO:0000244|PubMed:16964243}.
FT   MOD_RES    2069   2069       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692}.
FT   MOD_RES    2071   2071       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692}.
FT   MOD_RES    2182   2182       Phosphoserine.
FT                                {ECO:0000244|PubMed:18220336}.
FT   MOD_RES    2200   2200       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332}.
FT   MOD_RES    2202   2202       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q09XV5}.
FT   MOD_RES    2204   2204       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q09XV5}.
FT   MOD_RES    2211   2211       Phosphoserine.
FT                                {ECO:0000244|PubMed:18220336}.
FT   MOD_RES    2215   2215       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q09XV5}.
FT   MOD_RES    2223   2223       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9JIX5}.
FT   MOD_RES    2519   2519       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:23186163}.
FT   CROSSLNK    609    609       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000255|HAMAP-Rule:MF_03071}.
FT   CROSSLNK   2025   2025       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   CROSSLNK   2256   2256       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:25218447}.
FT   VAR_SEQ       1    281       MADPIMDLFDDPNLFGLDSLTDDSFNQVTQDPIEEALGLPS
FT                                SLDSLDQMNQDGGGGDVGNSSASELVPPPEETAPTELSKES
FT                                TAPAPESITLHDYTTQPASQEQPAQPVLQTSTPTSGLLQVS
FT                                KSQEILSQGNPFMGVSATAVSSSSAGGQPPQSAPKIVILKA
FT                                PPSSSVTGAHVAQIQAQGITSTAQPLVAGTANGGKVTFTKV
FT                                LTGTPLRPGVSIVSGNTVLAAKVPGNQAAVQRIVQPSRPVK
FT                                QLVLQPVKGSAPAGNPGATGPPLKPAVTLTSTPTQ -> MK
FT                                (in isoform 2).
FT                                {ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_017270.
FT   VARIANT     744    744       V -> I (in AUTS18; unknown pathological
FT                                significance; dbSNP:rs996150988).
FT                                {ECO:0000269|PubMed:26637798}.
FT                                /FTId=VAR_078704.
FT   VARIANT    2498   2498       Missing (in AUTS18).
FT                                {ECO:0000269|PubMed:23160955}.
FT                                /FTId=VAR_069573.
FT   MUTAGEN     842    842       K->R: Abolishes ATPase activity.
FT                                {ECO:0000269|PubMed:18378692}.
FT   CONFLICT    594    594       T -> A (in Ref. 1; CAH18170).
FT                                {ECO:0000305}.
FT   CONFLICT   1008   1008       D -> N (in Ref. 1; CAH18170).
FT                                {ECO:0000305}.
FT   CONFLICT   2481   2481       P -> Q (in Ref. 1; CAH18170).
FT                                {ECO:0000305}.
FT   CONFLICT   2568   2568       M -> I (in Ref. 8; AAH36920).
FT                                {ECO:0000305}.
FT   STRAND     2311   2314       {ECO:0000244|PDB:2CKA}.
FT   STRAND     2317   2319       {ECO:0000244|PDB:2CKA}.
FT   TURN       2320   2322       {ECO:0000244|PDB:2CKA}.
FT   HELIX      2328   2330       {ECO:0000244|PDB:2DL6}.
FT   HELIX      2334   2343       {ECO:0000244|PDB:2CKA}.
FT   STRAND     2347   2349       {ECO:0000244|PDB:2CKA}.
FT   HELIX      2351   2359       {ECO:0000244|PDB:2CKA}.
SQ   SEQUENCE   2581 AA;  290519 MW;  379F09DC6F814851 CRC64;
     MADPIMDLFD DPNLFGLDSL TDDSFNQVTQ DPIEEALGLP SSLDSLDQMN QDGGGGDVGN
     SSASELVPPP EETAPTELSK ESTAPAPESI TLHDYTTQPA SQEQPAQPVL QTSTPTSGLL
     QVSKSQEILS QGNPFMGVSA TAVSSSSAGG QPPQSAPKIV ILKAPPSSSV TGAHVAQIQA
     QGITSTAQPL VAGTANGGKV TFTKVLTGTP LRPGVSIVSG NTVLAAKVPG NQAAVQRIVQ
     PSRPVKQLVL QPVKGSAPAG NPGATGPPLK PAVTLTSTPT QGESKRITLV LQQPQSGGPQ
     GHRHVVLGSL PGKIVLQGNQ LAALTQAKNA QGQPAKVVTI QLQVQQPQQK IQIVPQPPSS
     QPQPQQPPST QPVTLSSVQQ AQIMGPGQSP GQRLSVPVKV VLQPQAGSSQ GASSGLSVVK
     VLSASEVAAL SSPASSAPHS GGKTGMEENR RLEHQKKQEK ANRIVAEAIA RARARGEQNI
     PRVLNEDELP SVRPEEEGEK KRRKKSAGER LKEEKPKKSK TSGASKTKGK SKLNTITPVV
     GKKRKRNTSS DNSDVEVMPA QSPREDEESS IQKRRSNRQV KRKKYTEDLD IKITDDEEEE
     EVDVTGPIKP EPILPEPVQE PDGETLPSMQ FFVENPSEED AAIVDKVLSM RIVKKELPSG
     QYTEAEEFFV KYKNYSYLHC EWATISQLEK DKRIHQKLKR FKTKMAQMRH FFHEDEEPFN
     PDYVEVDRIL DESHSIDKDN GEPVIYYLVK WCSLPYEDST WELKEDVDEG KIREFKRIQS
     RHPELKRVNR PQASAWKKLE LSHEYKNRNQ LREYQLEGVN WLLFNWYNRQ NCILADEMGL
     GKTIQSIAFL QEVYNVGIHG PFLVIAPLST ITNWEREFNT WTEMNTIVYH GSLASRQMIQ
     QYEMYCKDSR GRLIPGAYKF DALITTFEMI LSDCPELREI EWRCVIIDEA HRLKNRNCKL
     LDSLKHMDLE HKVLLTGTPL QNTVEELFSL LHFLEPSQFP SESEFLKDFG DLKTEEQVQK
     LQAILKPMML RRLKEDVEKN LAPKQETIIE VELTNIQKKY YRAILEKNFS FLSKGAGHTN
     MPNLLNTMME LRKCCNHPYL INGAEEKILT EFREACHIIP HDFHLQAMVR SAGKLVLIDK
     LLPKLKAGGH KVLIFSQMVR CLDILEDYLI QRRYLYERID GRVRGNLRQA AIDRFSKPDS
     DRFVFLLCTR AGGLGINLTA ADTCIIFDSD WNPQNDLQAQ ARCHRIGQSK AVKVYRLITR
     NSYEREMFDK ASLKLGLDKA VLQSMSGRDG NITGIQQFSK KEIEDLLRKG AYAAIMEEDD
     EGSKFCEEDI DQILLRRTTT ITIESEGKGS TFAKASFVAS ENRTDISLDD PNFWQKWAKK
     ADLDMDLLNS KNNLVIDTPR VRKQTRHFST LKDDDLVEFS DLESEDDERP RSRRHDRHHA
     YGRTDCFRVE KHLLVYGWGR WRDILSHGRF KRRMTERDVE TICRAILVYC LLHYRGDENI
     KGFIWDLISP AENGKTKELQ NHSGLSIPVP RGRKGKKVKS QSTFDIHKAD WIRKYNPDTL
     FQDESYKKHL KHQCNKVLLR VRMLYYLRQE VIGDQAEKVL GGAIASEIDI WFPVVDQLEV
     PTTWWDSEAD KSLLIGVFKH GYEKYNTMRA DPALCFLEKA GRPDDKAIAA EHRVLDNFSD
     IVEGVDFDKD CEDPEYKPLQ GPPKDQDDEG DPLMMMDEEI SVIDGDEAQV TQQPGHLFWP
     PGSALTARLR RLVTAYQRSY KREQMKIEAA ERGDRRRRRC EAAFKLKEIA RREKQQRWTR
     REQTDFYRVV STFGVEYDPD TMQFHWDRFR TFARLDKKTD ESLTKYFHGF VAMCRQVCRL
     PPAAGDEPPD PNLFIEPITE ERASRTLYRI ELLRRLREQV LCHPLLEDRL ALCQPPGPEL
     PKWWEPVRHD GELLRGAARH GVSQTDCNIM QDPDFSFLAA RMNYMQNHQA GAPAPSLSRC
     STPLLHQQYT SRTASPLPLR PDAPVEKSPE ETATQVPSLE SLTLKLEHEV VARSRPTPQD
     YEMRVSPSDT TPLVSRSVPP VKLEDEDDSD SELDLSKLSP SSSSSSSSSS SSSSTDESED
     EKEEKLTDQS RSKLYDEESL LSLTMSQDGF PNEDGEQMTP ELLLLQERQR ASEWPKDRVL
     INRIDLVCQA VLSGKWPSSR RSQEMVTGGI LGPGNHLLDS PSLTPGEYGD SPVPTPRSSS
     AASMAEEEAS AVSTAAAQFT KLRRGMDEKE FTVQIKDEEG LKLTFQKHKL MANGVMGDGH
     PLFHKKKGNR KKLVELEVEC MEEPNHLDVD LETRIPVINK VDGTLLVGED APRRAELEMW
     LQGHPEFAVD PRFLAYMEDR RKQKWQRCKK NNKAELNCLG MEPVQTANSR NGKKGHHTET
     VFNRVLPGPI APESSKKRAR RMRPDLSKMM ALMQGGSTGS LSLHNTFQHS SSGLQSVSSL
     GHSSATSASL PFMPFVMGGA PSSPHVDSST MLHHHHHHPH PHHHHHHHPG LRAPGYPSSP
     VTTASGTTLR LPPLQPEEDD DEDEEDDDDL SQGYDSSERD FSLIDDPMMP ANSDSSEDAD
     D
//
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