ID A0A2K5KJZ1_CERAT Unreviewed; 2589 AA.
AC A0A2K5KJZ1;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 30.
DE RecName: Full=Chromodomain-helicase-DNA-binding protein 8 {ECO:0000256|HAMAP-Rule:MF_03071};
DE Short=CHD-8 {ECO:0000256|HAMAP-Rule:MF_03071};
DE EC=3.6.4.12 {ECO:0000256|HAMAP-Rule:MF_03071};
DE AltName: Full=ATP-dependent helicase CHD8 {ECO:0000256|HAMAP-Rule:MF_03071};
GN Name=CHD8 {ECO:0000256|HAMAP-Rule:MF_03071,
GN ECO:0000313|Ensembl:ENSCATP00000001007.1};
OS Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Cercocebus.
OX NCBI_TaxID=9531 {ECO:0000313|Ensembl:ENSCATP00000001007.1, ECO:0000313|Proteomes:UP000233060};
RN [1] {ECO:0000313|Ensembl:ENSCATP00000001007.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
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:0000256|HAMAP-Rule:MF_03071}.
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:0000256|ARBA:ARBA00001665, ECO:0000256|HAMAP-
CC 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. {ECO:0000256|HAMAP-
CC Rule:MF_03071}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|HAMAP-Rule:MF_03071}.
CC Note=Localizes to the promoter regions of several CTNNB1-responsive
CC genes. Also present at known CTCF target sites. {ECO:0000256|HAMAP-
CC Rule:MF_03071}.
CC -!- PTM: Sumoylated. {ECO:0000256|HAMAP-Rule:MF_03071}.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily.
CC {ECO:0000256|HAMAP-Rule:MF_03071}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_03071}.
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DR RefSeq; XP_011932851.1; XM_012077461.1.
DR RefSeq; XP_011932853.1; XM_012077463.1.
DR RefSeq; XP_011932854.1; XM_012077464.1.
DR RefSeq; XP_011932857.1; XM_012077467.1.
DR STRING; 9531.ENSCATP00000001007; -.
DR Ensembl; ENSCATT00000005437.1; ENSCATP00000001007.1; ENSCATG00000004861.1.
DR GeneID; 105593904; -.
DR KEGG; caty:105593904; -.
DR CTD; 57680; -.
DR GeneTree; ENSGT00940000153649; -.
DR OrthoDB; 22878at2759; -.
DR Proteomes; UP000233060; Unplaced.
DR Bgee; ENSCATG00000004861; Expressed in cerebellum and 12 other cell types or tissues.
DR GO; GO:0071339; C:MLL1 complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0035064; F:methylated histone binding; IEA:Ensembl.
DR GO; GO:0002039; F:p53 binding; IEA:UniProtKB-UniRule.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IEA:Ensembl.
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 CDD; cd18668; CD1_tandem_CHD5-9_like; 1.
DR CDD; cd18663; CD2_tandem_CHD5-9_like; 1.
DR CDD; cd18060; DEXHc_CHD8; 1.
DR CDD; cd18793; SF2_C_SNF; 1.
DR Gene3D; 2.40.50.40; -; 2.
DR Gene3D; 3.40.5.120; -; 1.
DR Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 3.40.50.10810; Tandem AAA-ATPase domain; 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; IPR049730; SNF2/RAD54-like_C.
DR InterPro; IPR000330; SNF2_N.
DR PANTHER; PTHR46850; CHROMODOMAIN-HELICASE-DNA-BINDING PROTEIN 9; 1.
DR PANTHER; PTHR46850:SF3; DNA HELICASE; 1.
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; BRK domain-like; 1.
DR SUPFAM; SSF54160; Chromo domain-like; 2.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR PROSITE; PS50013; CHROMO_2; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 3: Inferred from homology;
KW Activator {ECO:0000256|HAMAP-Rule:MF_03071};
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|HAMAP-
KW Rule:MF_03071};
KW Chromatin regulator {ECO:0000256|ARBA:ARBA00022853, ECO:0000256|HAMAP-
KW Rule:MF_03071};
KW DNA-binding {ECO:0000256|ARBA:ARBA00023125, ECO:0000256|HAMAP-
KW Rule:MF_03071}; Helicase {ECO:0000256|HAMAP-Rule:MF_03071};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_03071};
KW Isopeptide bond {ECO:0000256|HAMAP-Rule:MF_03071};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|HAMAP-
KW Rule:MF_03071}; Nucleus {ECO:0000256|HAMAP-Rule:MF_03071};
KW Reference proteome {ECO:0000313|Proteomes:UP000233060};
KW Repeat {ECO:0000256|ARBA:ARBA00022737, ECO:0000256|HAMAP-Rule:MF_03071};
KW Repressor {ECO:0000256|HAMAP-Rule:MF_03071};
KW Transcription {ECO:0000256|ARBA:ARBA00023163, ECO:0000256|HAMAP-
KW Rule:MF_03071};
KW Transcription regulation {ECO:0000256|ARBA:ARBA00023015, ECO:0000256|HAMAP-
KW Rule:MF_03071}; Ubl conjugation {ECO:0000256|HAMAP-Rule:MF_03071};
KW Wnt signaling pathway {ECO:0000256|ARBA:ARBA00022687, ECO:0000256|HAMAP-
KW Rule:MF_03071}.
FT DOMAIN 724..790
FT /note="Chromo"
FT /evidence="ECO:0000259|PROSITE:PS50013"
FT DOMAIN 823..997
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000259|PROSITE:PS51192"
FT DOMAIN 1137..1288
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51194"
FT REGION 21..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..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 1700..1720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1999..2124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2197..2237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2489..2589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..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 1700..1718
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2083..2102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2103..2123
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2221..2237
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2499..2519
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2544..2561
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 609
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03071"
SQ SEQUENCE 2589 AA; 291409 MW; 42A92C951363231B CRC64;
MADPIMDLFD DPNLFGLDSL TDDSFNQVTQ DPIEEALGLP SSLDSLDQMN QDGGGGDVGN
SSASELVPPP EETAPTELPK ESTAPAPESI TLHDYTTQPA SQEQPAQPVL QTSTPTSGLL
QVSKSQEILS QGNPFMGVSA TAVSSSSVGG QPPQSAPKIV ILKAPPSSSV TGAHVAQIQA
QGITSTAQPL VAGTANGGKV TFTKVLTGTP LRPGVSIVSG NTVLAAKVPG NQAAVQRIVQ
PSRPVKQLVL QPVKGPAPAG 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 LKEEKPKKNK TSGTSKTKGK 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 NHSVFDVSPF PGLSIPVPRG RKGKKVKSQS TFDIHKADWI
RKYNPDTLFQ DESYKKHLKH QCNKVLLRVR MLYYLRQEVI GDQAEKVLGG AIASEIDIWF
PVVDQLEVPT TWWDSEADKS LLIGVFKHGY EKYNTMRADP ALCFLEKAGR PDDKAIAAEH
RVLDNFSDIV EGVDFDKDCE DPEYKPLQGP PKDQDDEGDP LMMMDEEISV IDGDEAQVTQ
QPGHLFWPPG SALTARLRRL VTAYQRSYKR EQMKIEAAER GDRRRRRCEA AFKLKEIARR
EKQQRWTRRE QTDFYRVVST FGVEYDPDTM QFHWDRFRTF ARLDKKTDES LTKYFHGFVA
MCRQVCRLPP AAGDEPPDPN LFIEPITEER ASRTLYRIEL LRRLREQVLC HPLLEDRLAL
CQPPGPELPK WWEPVRHDGE LLRGAARHGV SQTDCNIMQD PDFSFLAARM NYMQNHQAGA
PAPSLSRCST PLLHQQYTSR TASPLPLRPD APVEKSPEET AAQVPSLESL TLKLEHEVVA
RSRPTPQDYE MRVAPSDTTP LVSRSVPPVK LEDEDDSDSE LDLSKLSPSS SSSSSSSSSS
SSTDESEDEK EEKLTDQSRS KLYDEESLLS LTMSQDGFPN EDGEQMTPEL LLLQERQRAS
EWPKDRVLIN RIDLVCQAVL SGKWPSSRRS QEMVTGGILG PGNHLLDSPS LTPGEYGDSP
VPTPRSSSAA SMAEEEASAV TTAAAQFTKL RRGIDEKEFT VQIKDEEGLK LTFQKHKLMA
NGVMGDGHPL FHKKKGNRKK LVELEVECME EPNHLDVDLE TRIPVINKVD GTLLVGEDAP
RRAELEMWLQ GHPEFAVDPR FLAYMEDRRK QKWQRCKKNN KAELNCLGME PVQTANSRNG
KKGHHTETVF NRVLPGPIAP ESSKKRARRM RPDLSKMMAL MQGGSTGSLS LHNTFQHSSS
GLQSVSSLGH SSATSASLPF MPFVMGGAAS SPHVDSSTML HHHHHHPHPH HHHHHHPGLR
APGYPSSPAT TASGTTLRLP PLQPEEDDDE DEEDDDDLSQ GYDSSERDFS LIDDPMMPAN
SDSSEDADD
//
