Q9JIX5 (CHD8_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chromodomain-helicase-DNA-binding protein 8
Short name=CHD-8
EC=3.6.4.12

Alternative name(s):
ATP-dependent helicase CHD8
Axis duplication inhibitor
Short name=Duplin

Gene names

Name:

Chd8

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	2581 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA helicase that acts as a chromatin remodeling factor and regulates transcription. Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Ref.3 Ref.4
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Interacts with p53/TP53, histone H1 and CTCF. Component of some MLL1/MLL complex, at least composed of the core components MLL, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components C17orf49, CHD8, E2F6, HSP70, IN80C, KIAA1267, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with CHD7 By similarity. Interacts with CTNNB1 and PIAS3. Ref.1 Ref.4
Subcellular location	Nucleus. Note: Localizes to the promoter regions of several CTNNB1-responsive genes. Also present at known CTCF target sites By similarity. Ref.1 Ref.3
Post-translational modification	Sumoylated. Ref.4
Sequence similarities	Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily. Contains 2 chromo domains. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Activator Chromatin regulator Helicase Hydrolase Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ATP-dependent chromatin remodeling Inferred from sequence or structural similarity. Source: UniProtKB canonical Wnt receptor signaling pathway Inferred from direct assay Ref.1Ref.3. Source: UniProtKB negative regulation of Wnt receptor signaling pathway Inferred from direct assay Ref.1Ref.3Ref.4. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.1Ref.3. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase III promoter Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	MLL1 complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB DNA binding Inferred from sequence or structural similarity. Source: UniProtKB DNA helicase activity Inferred from sequence or structural similarity. Source: UniProtKB DNA-dependent ATPase activity Inferred from sequence or structural similarity. Source: UniProtKB armadillo repeat domain binding Inferred from physical interaction Ref.1. Source: RGD beta-catenin binding Inferred from direct assay Ref.1Ref.3. Source: UniProtKB methylated histone residue binding Inferred from sequence or structural similarity. Source: UniProtKB p53 binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9JIX5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9JIX5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     743-749: PVIYYLV → VSWAQRV
     750-2581: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2581	2581	Chromodomain-helicase-DNA-binding protein 8		PRO_0000367311
Regions
	Domain	642 – 709	68	Chromo 1
	Domain	724 – 790	67	Chromo 2
	Domain	823 – 997	175	Helicase ATP-binding
	Domain	1137 – 1288	152	Helicase C-terminal
	Nucleotide binding	836 – 843	8	ATP By similarity
	Motif	948 – 951	4	DEAH box
	Compositional bias	292 – 410	119	Gln-rich
	Compositional bias	1775 – 1779	5	Poly-Arg
	Compositional bias	2068 – 2097	30	Ser-rich
	Compositional bias	2493 – 2508	16	His-rich
	Compositional bias	2538 – 2581	44	Asp-rich
Amino acid modifications
	Modified residue	537	1	Phosphothreonine By similarity
	Modified residue	550	1	Phosphoserine By similarity
	Modified residue	553	1	Phosphoserine By similarity
	Modified residue	562	1	Phosphoserine By similarity
	Modified residue	1398	1	Phosphothreonine By similarity
	Modified residue	1420	1	Phosphoserine By similarity
	Modified residue	1424	1	Phosphoserine By similarity
	Modified residue	1976	1	Phosphoserine By similarity
	Modified residue	1993	1	Phosphothreonine By similarity
	Modified residue	1995	1	Phosphoserine By similarity
	Modified residue	2008	1	Phosphoserine By similarity
	Modified residue	2068	1	Phosphoserine By similarity
	Modified residue	2070	1	Phosphoserine By similarity
	Modified residue	2182	1	Phosphoserine By similarity
	Modified residue	2200	1	Phosphoserine By similarity
	Modified residue	2202	1	Phosphoserine By similarity
	Modified residue	2211	1	Phosphoserine By similarity
	Modified residue	2518	1	Phosphoserine By similarity
	Modified residue	2519	1	Phosphoserine By similarity
	Cross-link	609		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.4
Natural variations
	Alternative sequence	743 – 749	7	PVIYYLV → VSWAQRV in isoform 2.		VSP_036678
	Alternative sequence	750 – 2581	1832	Missing in isoform 2.		VSP_036679
Experimental info
	Mutagenesis	457	1	K → R: Does not affect sumoylation status. Ref.4
	Mutagenesis	512	1	K → R: Does not affect sumoylation status. Ref.4
	Mutagenesis	609	1	K → R: Induces a decrease in sumoylation status. Ref.4
	Mutagenesis	654	1	K → R: Does not affect sumoylation status. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 24, 2009. Version 2. Checksum: 4E2BBE55D7A2CD3D	FASTA	2,581	290,692
	10 20 30 40 50 60 MADPIMDLFD DPNLFGLDSL TDDSFNQVTQ DPIEEALGLP SSLDSLDQMN QDGGSGDVGN 70 80 90 100 110 120 SSASDLVPPP EETASTELPK ESTAPAPESL TLHDYTTQPT SQEQPAQPVL QTSTPTSGLL 130 140 150 160 170 180 QVSKSQEILS QGNPFMGVSA TAVSPSNTGG QPSQSAPKIV ILKAPPNSSV TGAHVAQIQA 190 200 210 220 230 240 QGITSTAQPL VAGTANGGKV TFTKVLTGTP LRPGVSIVSG NTVLATKVPG NQAAVQRIVQ 250 260 270 280 290 300 PSRPVKQLVL QPVKGSAPAG NPGATGPPLK PAVTLTSTPA QGESKRITLV LQQPQSGGPQ 310 320 330 340 350 360 GHRHVVLGSL PGKIVLQGNQ LAALTQAKSA QGQPAKVVTI QLQVQQPQQK IQIVPQPPSS 370 380 390 400 410 420 QPQPQPPPSA QPLTLSSVQQ AQIMGPGQNP GQRLSVPLKM VLQPQAGSSQ GASSGLSVVK 430 440 450 460 470 480 VLSASEVAAL SSPASCAPHT AGKTGMEENR RLEHQKKQEK ANRIVAEAIA RARARGEQNI 490 500 510 520 530 540 PRVLNEDELP SVRPEEEGEK KRRKKSSGER LKEEKPKKSK TAAASKTKGK SKLNTITPVV 550 560 570 580 590 600 GKKRKRNTSS DNSDVEVMPA QSPREDEESS IQKRRSNRQV KRKKYTEDLD IKITDDEEEE 610 620 630 640 650 660 EVDVTGPIKP EPILPEPVPE PDGETLPSMQ FFVENPSEED AAIVDKVLSM RVVKKELPSG 670 680 690 700 710 720 QYTEAEEFFV KYKNYSYLHC EWATISQLEK DKRIHQKLKR FKTKMAQMRH FFHEDEEPFN 730 740 750 760 770 780 PDYVEVDRIL DESHSVDKDN GEPVIYYLVK WCSLPYEDST WELKEDVDEG KIREFKRIQS 790 800 810 820 830 840 RHPELKRVNR PQANAWKKLE LSHEYKNRNQ LREYQLEGVN WLLFNWYNRQ NCILADEMGL 850 860 870 880 890 900 GKTIQSIAFL QEVYNVGIHG PFLVIAPLST ITNWEREFNT WTEMNTIVYH GSLASRQMIQ 910 920 930 940 950 960 QYEMYCKDSR GRLIPGAYKF DALITTFEMI LSDCPELREI EWRCVIIDEA HRLKNRNCKL 970 980 990 1000 1010 1020 LDSLKHMDLE HKVLLTGTPL QNTVEELFSL LHFLEPSQFP SESEFLKDFG DLKTEEQVQK 1030 1040 1050 1060 1070 1080 LQAILKPMML RRLKEDVEKN LAPKQETIIE VELTNIQKKY YRAILEKNFS FLSKGAGHTN 1090 1100 1110 1120 1130 1140 MPNLLNTMME LRKCCNHPYL INGAEEKILM EFREACHIIP QDFHLQAMVR SAGKLVLIDK 1150 1160 1170 1180 1190 1200 LLPKLKAGGH KVLIFSQMVR CLDILEDYLI QRRYLYERID GRVRGNLRQA AIDRFSKPDS 1210 1220 1230 1240 1250 1260 DRFVFLLCTR AGGLGINLTA ADTCIIFDSD WNPQNDLQAQ ARCHRIGQSK AVKVYRLITR 1270 1280 1290 1300 1310 1320 NSYEREMFDK ASLKLGLDKA VLQSMSGRDG NITGIQQFSK KEIEDLLRKG AYAAIMEEDD 1330 1340 1350 1360 1370 1380 EGSKFCEEDI DQILLRRTTT ITIESEGKGS TFAKASFVAS ENRTDISLDD PNFWQKWAKK 1390 1400 1410 1420 1430 1440 ADLDMDLLNS KNNLVIDTPR VRKQTRHFST LKDDDLVEFS DLESEDDERP RSRRHDRHHT 1450 1460 1470 1480 1490 1500 YGRTDCFRVE KHLLVYGWGR WRDILSHGRF KRRMTERDVE TICRAILVYC LLHYRGDENI 1510 1520 1530 1540 1550 1560 KSFIWDLISP AENGKTKELQ NHSGLSIPVP RGRKGKKVKS QSTFDIHKAD WIRKYNPDTL 1570 1580 1590 1600 1610 1620 FQDESYKKHL KHQCNKVLLR VRMLYYLRQE VIGDQAEKVL GGAIASEIDI WFPVVDQLEV 1630 1640 1650 1660 1670 1680 PTTWWDSEAD KSLLIGVFKH GYEKYNTMRA DPALCFLEKA GRPDDKAIAA EHRVLDNFSD 1690 1700 1710 1720 1730 1740 LVEGIDFDKD CEDPEYKPLQ GPPKDPDDEG DPLMMMDEEI SVIDGDEAPV TQQPGHLFWP 1750 1760 1770 1780 1790 1800 PGSALTARLR RLVTAYQRSY KREQMKIEAA ERGDRRRRRC EAAFKLKEIA RREKQQRWTR 1810 1820 1830 1840 1850 1860 REQTDFYRVV STFGVEYDPD NMQFHWDRFR TFARLDKKTD ESLTKYFHGF VAMCRQVCRL 1870 1880 1890 1900 1910 1920 PPAAGDEPPD PNLFIEPITE ERASRTLYRI ELLRRLREQV LCHPLLEDRL ALCQPPGLEL 1930 1940 1950 1960 1970 1980 PKWWEPVRHD GELLRGAARH GVSQTDCNIM QDPDFSFLAA RMNYMQNHQA GASAASLSRC 1990 2000 2010 2020 2030 2040 STPLLHQQCT SRTASPSPLR PDVPAEKSPE ENAVQVPSLD SLTLKLEDEV VARSRLTPQD 2050 2060 2070 2080 2090 2100 YEIRVASSDT APLSRSVPPV KLEDDDDSDS ELDLSKLSPS SSSSSSSSSS SSSSDESEDE 2110 2120 2130 2140 2150 2160 KEEKLTADRS RPKLYDEESL LSLTMSQDGF PNEDGEQMTP ELLLLQERQR ASEWPKDRVL 2170 2180 2190 2200 2210 2220 INRIDLVCQA VLSGKWPSNR RSQEMTTGGI LGPGNHLLDS PSLTPGEYGD SPVPTPRSSS 2230 2240 2250 2260 2270 2280 AASMVEEEAS AVTTAAAQFT KLRRGMDEKE FTVQIKDEEG LKLTFQKHRL MANGVMGDGH 2290 2300 2310 2320 2330 2340 PLFHKKKGNR KKLVELEVEC MEEPNHLDVD LETRIPVINK VDGTLLVGDE APRRAELDMW 2350 2360 2370 2380 2390 2400 LQGHPEFAVD PRFLAYMEER RKQKWQRCKK NNKTELNCLG MEPVQPANSR NGKKGHYAET 2410 2420 2430 2440 2450 2460 AFNRVLPGPI APENSKKRVR RTRPDLSKMM ALMQGGSTGS LSLHNTFQHS SSNLQSVSSL 2470 2480 2490 2500 2510 2520 GHSSATSASL PFMPFVMGGA AAPPHVDSST MLHHHHHHPH PHHHHHHHPG LRTTGYPSSP 2530 2540 2550 2560 2570 2580 ATTTSGTALR LPTLQHEDDD EEEDEDDDDL SQGYDSSERD FSLIDDPMMP ANSDSSDDAD D
	Isoform 2 [UniParc]. Checksum: 3CAE4FF0BCF89D05	FASTA	749	80,667
	10 20 30 40 50 60 MADPIMDLFD DPNLFGLDSL TDDSFNQVTQ DPIEEALGLP SSLDSLDQMN QDGGSGDVGN 70 80 90 100 110 120 SSASDLVPPP EETASTELPK ESTAPAPESL TLHDYTTQPT SQEQPAQPVL QTSTPTSGLL 130 140 150 160 170 180 QVSKSQEILS QGNPFMGVSA TAVSPSNTGG QPSQSAPKIV ILKAPPNSSV TGAHVAQIQA 190 200 210 220 230 240 QGITSTAQPL VAGTANGGKV TFTKVLTGTP LRPGVSIVSG NTVLATKVPG NQAAVQRIVQ 250 260 270 280 290 300 PSRPVKQLVL QPVKGSAPAG NPGATGPPLK PAVTLTSTPA QGESKRITLV LQQPQSGGPQ 310 320 330 340 350 360 GHRHVVLGSL PGKIVLQGNQ LAALTQAKSA QGQPAKVVTI QLQVQQPQQK IQIVPQPPSS 370 380 390 400 410 420 QPQPQPPPSA QPLTLSSVQQ AQIMGPGQNP GQRLSVPLKM VLQPQAGSSQ GASSGLSVVK 430 440 450 460 470 480 VLSASEVAAL SSPASCAPHT AGKTGMEENR RLEHQKKQEK ANRIVAEAIA RARARGEQNI 490 500 510 520 530 540 PRVLNEDELP SVRPEEEGEK KRRKKSSGER LKEEKPKKSK TAAASKTKGK SKLNTITPVV 550 560 570 580 590 600 GKKRKRNTSS DNSDVEVMPA QSPREDEESS IQKRRSNRQV KRKKYTEDLD IKITDDEEEE 610 620 630 640 650 660 EVDVTGPIKP EPILPEPVPE PDGETLPSMQ FFVENPSEED AAIVDKVLSM RVVKKELPSG 670 680 690 700 710 720 QYTEAEEFFV KYKNYSYLHC EWATISQLEK DKRIHQKLKR FKTKMAQMRH FFHEDEEPFN 730 740 PDYVEVDRIL DESHSVDKDN GEVSWAQRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation." Sakamoto I., Kishida S., Fukui A., Kishida M., Yamamoto H., Hino S., Michiue T., Takada S., Asashima M., Kikuchi A. J. Biol. Chem. 275:32871-32878(2000) [PubMed: 10921920] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, INTERACTION WITH CTNNB1.
[2]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway." Kobayashi M., Kishida S., Fukui A., Michiue T., Miyamoto Y., Okamoto T., Yoneda Y., Asashima M., Kikuchi A. J. Biol. Chem. 277:5816-5822(2002) [PubMed: 11744694] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[4]	"Suppression of STAT3 activity by Duplin, which is a negative regulator of the Wnt signal." Yamashina K., Yamamoto H., Chayama K., Nakajima K., Kikuchi A. J. Biochem. 139:305-314(2006) [PubMed: 16452319] [Abstract] Cited for: FUNCTION, SUMOYLATION AT LYS-609, INTERACTION WITH PIAS3, MUTAGENESIS OF LYS-457; LYS-512; LYS-609 AND LYS-654.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF169825 mRNA. Translation: AAF89678.1. CH474040 Genomic DNA. Translation: EDL88472.1.
IPI	IPI00201110. IPI00923717.
RefSeq	NP_075222.2. NM_022933.2.
UniGene	Rn.98337.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9JIX5.
PTM databases
PhosphoSite	Q9JIX5.
Proteomic databases
PRIDE	Q9JIX5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000022593; ENSRNOP00000022593; ENSRNOG00000025011.
GeneID	65027.
KEGG	rno:65027.
UCSC	AF169825. rat.
Organism-specific databases
CTD	57680.
RGD	620696. Chd8.
Phylogenomic databases
eggNOG	roNOG09554.
GeneTree	ENSGT00560000077077.
HOVERGEN	HBG107676.
OrthoDB	EOG4ZPDTC.
Gene expression databases
Genevestigator	Q9JIX5.
Family and domain databases
InterPro	IPR006576. BRK_domain. IPR023780. Chromo_domain. IPR000953. Chromo_domain/shadow. IPR016197. Chromodomain-like. IPR014001. DEAD-like_helicase. IPR001650. Helicase_C. IPR000330. SNF2_N. [Graphical view]
KO	K04494.
Pfam	PF07533. BRK. 2 hits. PF00385. Chromo. 2 hits. PF00271. Helicase_C. 1 hit. PF00176. SNF2_N. 1 hit. [Graphical view]
SMART	SM00592. BRK. 2 hits. SM00298. CHROMO. 2 hits. SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view]
SUPFAM	SSF54160. Chromodomain-like. 2 hits.
PROSITE	PS00598. CHROMO_1. False negative. PS50013. CHROMO_2. 1 hit. PS00690. DEAH_ATP_HELICASE. False negative. PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

CHD8_RAT

Accession

Primary (citable) accession number: Q9JIX5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 24, 2009
Last sequence update:	March 24, 2009
Last modified:	January 25, 2012
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program