ID G3U9U5_LOXAF Unreviewed; 2565 AA.
AC G3U9U5;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 27-MAR-2024, entry version 63.
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:ENSLAFP00000024603.1};
OS Loxodonta africana (African elephant).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Afrotheria; Proboscidea; Elephantidae; Loxodonta.
OX NCBI_TaxID=9785 {ECO:0000313|Ensembl:ENSLAFP00000024603.1, ECO:0000313|Proteomes:UP000007646};
RN [1] {ECO:0000313|Ensembl:ENSLAFP00000024603.1, ECO:0000313|Proteomes:UP000007646}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000024603.1,
RC ECO:0000313|Proteomes:UP000007646};
RA Di Palma F., Heiman D., Young S., Johnson J., Lander E.S., Lindblad-Toh K.;
RT "The Genome Sequence of Loxodonta africana (African elephant).";
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSLAFP00000024603.1}
RP IDENTIFICATION.
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000024603.1};
RG Ensembl;
RL Submitted (NOV-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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR Ensembl; ENSLAFT00000024249.2; ENSLAFP00000024603.1; ENSLAFG00000009358.4.
DR GeneTree; ENSGT00940000153649; -.
DR HOGENOM; CLU_000315_5_2_1; -.
DR Proteomes; UP000007646; Unassembled WGS sequence.
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:InterPro.
DR GO; GO:0008013; F:beta-catenin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0042393; F:histone binding; IEA:UniProtKB-UniRule.
DR GO; GO:0002039; F:p53 binding; IEA:UniProtKB-UniRule.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:UniProtKB-UniRule.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:UniProtKB-UniRule.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IEA:UniProtKB-UniRule.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IEA:UniProtKB-UniRule.
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:UP000007646};
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 723..789
FT /note="Chromo"
FT /evidence="ECO:0000259|PROSITE:PS50013"
FT DOMAIN 822..996
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000259|PROSITE:PS51192"
FT DOMAIN 1136..1287
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51194"
FT REGION 36..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 252..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 348..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 595..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1691..1711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2026..2115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2189..2227
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2481..2565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..388
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 443..465
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..520
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 559..582
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1691..1709
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2039..2053
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2074..2093
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2094..2115
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2500..2514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2521..2537
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 608
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03071"
SQ SEQUENCE 2565 AA; 288549 MW; F648A0CB4EABADD3 CRC64;
MADPIMDLFD DPNLFGLDSL TDDSFNQVTQ DPIVEALGLP SSLDPLDQMN QDGGGGDVGN
SSTSDLVPPP EETAPTEIPK ESAVPAPESL TLHDYTTQPA SQEQPAQPIL QTTMPTSGLL
QVSKSQEILS QGNPFMGVSA TAVSSSTGGQ PPQSAPKIVI LKAPPSSSVT GAHVAQIQAQ
GITSTAQPLV AGTANGGKVT FTKVLTGTPL RPGVSIVSGN TVLAAKVPGN QATVQRIVQP
SRPVKQLVLQ PVKGSAPAGN PGATGPPLKP AVTLTSTPTQ GESKRITLVL QQPQSGGPQG
HRHVVLGSLP GKIVLQGNQL AALTQAKNAQ GQPAKVVTIQ LQVQQPQQKI QIVPQPPSSQ
PQPQQPPSTQ PVTLSSVQQA QIMGPGQSPG QRLSVPLKVV LQPQAGSSQG ASSGLSVVKV
LSASEVAALS SPASSAPHTG AKTGMEENRR LEHQKKQEKA NRIVAEAIAR ARARGEQNIP
RVLNEDELPS VRPEEEGEKK RRKKGSGERL KEEKPKKNKT SGTSKTKGKS KLNTITPVVG
KKRKRNTSSD NSDVEVMPAQ SPREDEESSI QKRRSNRQVK RKKYTEDLDI KITDDEEEEE
VDVTGPIKPE PILPEPVQEP DGETLPSMQF FVENPSEEDA AIVDKVLSMR VVKKELPSGQ
YTEAEEFFVK YKNYSYLHCE WATISQLEKD KRIHQKLKRF KTKMAQMRHF FHEDEEPFNP
DYVEVDRILD ESHSIDKDNG EPVIYYLVKW CSLPYEDSTW ELKEDVDEGK IREFKRIQSR
HPELKRVNRP QASAWKKLEL SHEYKNRNQL REYQLEGVNW LLFNWYNRQN CILADEMGLG
KTIQSIAFLQ EVYNVGIHGP FLVIAPLSTI TNWEREFNTW TEMNTIVYHG SLASRQMIQQ
YEMYCKDSRG RLIPGAYKFD ALITTFEMIL SDCPELREIE WRCVIIDEAH RLKNRNCKLL
DSLKHMDLEH KVLLTGTPLQ NTVEELFSLL HFLEPSQFPS ESEFLKDFGD LKTEEQVQKL
QAILKPMMLR RLKEDVEKNL APKQETIIEV ELTNIQKKYY RAILEKNFSF LSKGAGHTNM
PNLLNTMMEL RKCCNHPYLI NGAEEKILTE FREACHIIPH DFHLQAMVRS AGKLVLIDKL
LPKLKAGGHK VLIFSQMVRC LDILEDYLIQ RRYLYERIDG RVRGNLRQAA IDRFSKPDSD
RFVFLLCTRA GGLGINLTAA DTCIIFDSDW NPQNDLQAQA RCHRIGQSKA VKVYRLITRN
SYEREMFDKA SLKLGLDKAV LQSMSGRDGN ITGIQQFSKK EIEDLLRKGA YAAIMEEDDE
GSKFCEEDID QILLRRTTTI TIESEGKGST FAKASFVASE NRTDISLDDP NFWQKWAKKA
DLDMDLLNSK NNLVIDTPRV RKQTRHFSTL KDDDLVEFSD LESEDDERPR SRRHDRHHAY
GRTDCFRVEK HLLVYGWGRW RDILSHGRFK RRMTERDVET ICRAILVYCL LHYRGDENIK
GFIWDLISPA ENGKTKELQN HSGLSIPVPR GRKGKKVKSQ STFDIHKADW IRKYNPDTLF
QDESYKKHLK HQCNKVLLRV RMLYYLRQEV IGDQAEKVLG GAIASEIDIW FPVVDQLEVP
TTWWDSEADK SLLIGVFKHG YEKYNTMRAD PALCFLEKAG RPDDKAIAAE HRVLDNFSDI
VEGVDFDKDC EDPEYKPLQG PPKDQDDEGD PLMMMDEEIS VIDGDEAQVT QQPGHLFWPP
GSALTARLRR LVTAYQRSYK REQMKIEAAE RGDRRRRRCE AAFKLKEIAR REKQQRWTRR
EQTDFYRVVS TFGVEYDPDT MQFHWDRFRT FARLDKKTDE SLTKYFHGFV AMCRQVCRLP
PAAGDEPPDP NLFIEPITEE RASRTLYRIE LLRRLREQVL CHPLLEDRLS LCQPPGPELP
KWWEPIRHDG ELLRGAARHG VSQTDCNIMQ DPDFSFLAAR MNYMQNYQAG APAPSLSRCS
TPLLHQQYTS RTASPLPLRL EAPVEKPPEE TAAQVPSLES LTLKLEHEVV GRSRPTPQDY
EMRVTSSDTA PLVSRSVPPV KLEDEDDSDS ELDLSKLSPS SSSSSSSSSS SSSTDESEDE
KEEKLTADPS RSKLYDEESL LSLTMSQDGF PNEDGEQMTP ELLMLQERQR ASEWPKDRVL
INRIDLVCQA VLSGKWPSSR RSQEMVTGGI LGPGNHLLDS PSLTPGEYGD SPVPTPRSSS
AASMAEEEAS AVSAAAAQFT KLRRGMDEKE FTVQIKDEEG LKLTFQKHKL MANGVMGDGH
PLFHKKKGNR KKLVELEVEC MEEPNHLDVD LETRIPVINK VDGTLLVGED APRRAELEMW
LQGHPEFAVD PRFLAYMEDR RKQKWQRCKK NNKAEMNCLG VEPVQTANSR NGKKGHHAET
VFNRVLPGHI APESSKKRSR RMRPDLSKMM ALMQGGGTGS LSLHNTFQHS SSGLQSLSSL
GHSSATSASL PFMPFVMGDA ASSPHVDSST MHPGLRATGY PSSPATTTSG TALRLPPLQP
AEDDEDEDEE DDDLSQGYDS SERDFSLIDD PMMPANSDSS EDADD
//
