CHD8_HUMAN
ID CHD8_HUMAN Reviewed; 2581 AA.
AC Q9HCK8; Q4G0D8; Q68DQ0; Q6DKH9; Q6P440; Q6ZNL7; Q8N3Z9; Q8NCY4; Q8TBR9;
AC Q96F26;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 5.
DT 03-AUG-2022, entry version 202.
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}; Synonyms=HELSNF1, KIAA1564;
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 [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., 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 [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., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., 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., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA 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. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT 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 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 project:
RT 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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT 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 remodeling.";
RL Mol. Cell 23:733-742(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2051, AND IDENTIFICATION BY
RP 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 phosphorylation
RT 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., 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, cognitive
RT 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., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT 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 beta-
RT 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 SCALE
RP 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., 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 [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 SPECTROMETRY
RP [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 syndrome.";
RL Hum. Mol. Genet. 19:2858-2866(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1420; SER-1424; SER-2008 AND
RP SER-2046, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1420; SER-1424; SER-2046;
RP SER-2069 AND SER-2071, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT 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 of a
RT 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 AND
RP SER-2519, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2256, AND IDENTIFICATION BY MASS
RP 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 MASS
RP 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 [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., Phelps I.G.,
RA Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B.,
RA Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K.,
RA Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M.,
RA 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 Implicates
RT Multiple Genetic Mechanisms.";
RL Neuron 88:910-917(2015).
CC -!- FUNCTION: DNA helicase that acts as a chromatin remodeling factor and
CC 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 histone H1
CC and preventing p53/TP53 transactivation activity. Acts as a negative
CC regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1)
CC activity. Negatively regulates CTNNB1-targeted gene expression by being
CC recruited specifically to the promoter regions of several CTNNB1
CC responsive genes. Involved in both enhancer blocking and epigenetic
CC remodeling at chromatin boundary via its interaction with CTCF. Acts as
CC a suppressor of STAT3 activity by suppressing the LIF-induced STAT3
CC transcriptional activity. Also acts as a transcription activator via
CC its interaction with ZNF143 by participating in efficient U6 RNA
CC polymerase III transcription. {ECO:0000255|HAMAP-Rule:MF_03071,
CC ECO:0000269|PubMed:17938208, 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 PIAS3.
CC Component of some MLL1/MLL complex, at least composed of the core
CC components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as
CC the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1,
CC LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2,
CC RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and
CC TEX10. Interacts with CHD7. Interacts with FAM124B (PubMed:23285124).
CC {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:15960975,
CC ECO:0000269|PubMed:16949368, ECO:0000269|PubMed:17938208,
CC ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:20453063,
CC ECO:0000269|PubMed:23285124}.
CC -!- INTERACTION:
CC Q9HCK8; O00154: ACOT7; NbExp=2; IntAct=EBI-1169146, EBI-948905;
CC Q9HCK8; Q9UBL3: ASH2L; NbExp=2; IntAct=EBI-1169146, EBI-540797;
CC Q9HCK8; Q15291: RBBP5; NbExp=2; IntAct=EBI-1169146, EBI-592823;
CC Q9HCK8; P61964: WDR5; NbExp=3; IntAct=EBI-1169146, EBI-540834;
CC Q9HCK8; O95365: ZBTB7A; NbExp=2; IntAct=EBI-1169146, EBI-2795384;
CC Q9HCK8-2; Q9P2D1: CHD7; NbExp=3; IntAct=EBI-4410319, EBI-3951683;
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-responsive
CC genes. Also present at known CTCF target sites. {ECO:0000255|HAMAP-
CC 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 -!- PTM: Sumoylated. {ECO:0000255|HAMAP-Rule:MF_03071}.
CC -!- DISEASE: Autism 18 (AUTS18) [MIM:615032]: A complex multifactorial,
CC pervasive developmental disorder characterized by impairments in
CC reciprocal social interaction and communication, restricted and
CC stereotyped patterns of interests and activities, and the presence of
CC developmental abnormalities by 3 years of age. Most individuals with
CC autism also manifest moderate intellectual disability.
CC {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:26637798}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- MISCELLANEOUS: Its gene is located in the 14q11.2 region of the genome
CC which is associated with developmental delay, cognitive impairment and
CC similar minor anomalies in some children, suggesting that it may be a
CC good candidate for the phenotype.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03071}.
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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 AlphaFoldDB; Q9HCK8; -.
DR SMR; Q9HCK8; -.
DR BioGRID; 121709; 136.
DR CORUM; Q9HCK8; -.
DR DIP; DIP-38021N; -.
DR ELM; Q9HCK8; -.
DR IntAct; Q9HCK8; 69.
DR MINT; Q9HCK8; -.
DR STRING; 9606.ENSP00000382863; -.
DR GlyGen; Q9HCK8; 3 sites, 2 O-linked glycans (3 sites).
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 Antibodypedia; 73; 131 antibodies from 21 providers.
DR DNASU; 57680; -.
DR Ensembl; ENST00000430710.8; ENSP00000406288.3; ENSG00000100888.15. [Q9HCK8-2]
DR Ensembl; ENST00000557364.6; ENSP00000451601.1; ENSG00000100888.15. [Q9HCK8-1]
DR Ensembl; ENST00000643469.1; ENSP00000495070.1; ENSG00000100888.15. [Q9HCK8-1]
DR Ensembl; ENST00000645929.1; ENSP00000494402.1; ENSG00000100888.15. [Q9HCK8-2]
DR Ensembl; ENST00000646647.2; ENSP00000495240.1; ENSG00000100888.15. [Q9HCK8-1]
DR GeneID; 57680; -.
DR KEGG; hsa:57680; -.
DR MANE-Select; ENST00000646647.2; ENSP00000495240.1; NM_001170629.2; NP_001164100.1.
DR UCSC; uc001war.3; human. [Q9HCK8-1]
DR CTD; 57680; -.
DR DisGeNET; 57680; -.
DR GeneCards; CHD8; -.
DR HGNC; HGNC:20153; CHD8.
DR HPA; ENSG00000100888; Low tissue specificity.
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 VEuPathDB; HostDB:ENSG00000100888; -.
DR eggNOG; KOG0384; Eukaryota.
DR GeneTree; ENSGT00940000153649; -.
DR HOGENOM; CLU_000315_5_2_1; -.
DR InParanoid; Q9HCK8; -.
DR OMA; IFSDPQF; -.
DR OrthoDB; 7181at2759; -.
DR PhylomeDB; Q9HCK8; -.
DR TreeFam; TF313572; -.
DR PathwayCommons; Q9HCK8; -.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR SignaLink; Q9HCK8; -.
DR SIGNOR; Q9HCK8; -.
DR BioGRID-ORCS; 57680; 142 hits in 1103 CRISPR screens.
DR ChiTaRS; CHD8; human.
DR EvolutionaryTrace; Q9HCK8; -.
DR GeneWiki; CHD8; -.
DR GenomeRNAi; 57680; -.
DR Pharos; Q9HCK8; Tbio.
DR PRO; PR:Q9HCK8; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9HCK8; protein.
DR Bgee; ENSG00000100888; Expressed in sural nerve and 194 other tissues.
DR ExpressionAtlas; Q9HCK8; baseline and differential.
DR Genevisible; Q9HCK8; HS.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
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:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; IDA:GO_Central.
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; IEA:UniProtKB-UniRule.
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:0007420; P:brain development; IMP:GO_Central.
DR GO; GO:0006338; P:chromatin remodeling; 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:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.40.5.120; -; 1.
DR Gene3D; 3.40.50.10810; -; 1.
DR Gene3D; 3.40.50.300; -; 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-rel_dom; 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; Disease variant;
KW DNA-binding; Helicase; Hydrolase; Isopeptide bond; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..2581
FT /note="Chromodomain-helicase-DNA-binding protein 8"
FT /id="PRO_0000080233"
FT DOMAIN 642..709
FT /note="Chromo 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT DOMAIN 724..790
FT /note="Chromo 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT DOMAIN 823..997
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT DOMAIN 1137..1288
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT REGION 22..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 596..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1692..1712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1789..2302
FT /note="Interaction with FAM124B"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071,
FT ECO:0000269|PubMed:23285124"
FT REGION 1991..2116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2189..2229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2481..2581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 948..951
FT /note="DEAH box"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT COMPBIAS 43..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..389
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..466
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..521
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 560..582
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1692..1710
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2041..2055
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2075..2094
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2095..2115
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2213..2229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2491..2511
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2536..2553
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 836..843
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1420
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1976
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1978
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1993
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1995
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIX5"
FT MOD_RES 2008
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 2046
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2051
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 2069
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 2071
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 2182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 2200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q09XV5"
FT MOD_RES 2204
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q09XV5"
FT MOD_RES 2211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 2215
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q09XV5"
FT MOD_RES 2223
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIX5"
FT MOD_RES 2519
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 609
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT CROSSLNK 2025
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 2256
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT VAR_SEQ 1..281
FT /note="MADPIMDLFDDPNLFGLDSLTDDSFNQVTQDPIEEALGLPSSLDSLDQMNQD
FT GGGGDVGNSSASELVPPPEETAPTELSKESTAPAPESITLHDYTTQPASQEQPAQPVLQ
FT TSTPTSGLLQVSKSQEILSQGNPFMGVSATAVSSSSAGGQPPQSAPKIVILKAPPSSSV
FT TGAHVAQIQAQGITSTAQPLVAGTANGGKVTFTKVLTGTPLRPGVSIVSGNTVLAAKVP
FT GNQAAVQRIVQPSRPVKQLVLQPVKGSAPAGNPGATGPPLKPAVTLTSTPTQ -> MK
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017270"
FT VARIANT 744
FT /note="V -> I (in AUTS18; unknown pathological
FT significance; dbSNP:rs996150988)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078704"
FT VARIANT 2498
FT /note="Missing (in AUTS18)"
FT /evidence="ECO:0000269|PubMed:23160955"
FT /id="VAR_069573"
FT MUTAGEN 842
FT /note="K->R: Abolishes ATPase activity."
FT /evidence="ECO:0000269|PubMed:18378692"
FT CONFLICT 594
FT /note="T -> A (in Ref. 1; CAH18170)"
FT /evidence="ECO:0000305"
FT CONFLICT 1008
FT /note="D -> N (in Ref. 1; CAH18170)"
FT /evidence="ECO:0000305"
FT CONFLICT 2481
FT /note="P -> Q (in Ref. 1; CAH18170)"
FT /evidence="ECO:0000305"
FT CONFLICT 2568
FT /note="M -> I (in Ref. 8; AAH36920)"
FT /evidence="ECO:0000305"
FT STRAND 2311..2314
FT /evidence="ECO:0007829|PDB:2CKA"
FT STRAND 2317..2319
FT /evidence="ECO:0007829|PDB:2CKA"
FT TURN 2320..2322
FT /evidence="ECO:0007829|PDB:2CKA"
FT HELIX 2328..2330
FT /evidence="ECO:0007829|PDB:2DL6"
FT HELIX 2334..2343
FT /evidence="ECO:0007829|PDB:2CKA"
FT STRAND 2347..2349
FT /evidence="ECO:0007829|PDB:2CKA"
FT HELIX 2351..2359
FT /evidence="ECO:0007829|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
