O95983 (MBD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methyl-CpG-binding domain protein 3

Alternative name(s):
Methyl-CpG-binding protein MBD3

Gene names

Name:

MBD3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	291 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Does not bind DNA by itself. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Ref.1 Ref.6 Ref.8
Subunit structure	Heterodimer with MBD2. Part of the NuRD and the MeCP1 complex. Binds HDAC1, MTA2, DNMT1, p66-alpha and p66-beta. Ref.6
Subcellular location	Nucleus. Note: Nuclear, in discrete foci. Ref.1
Sequence similarities	Contains 1 MBD (methyl-CpG-binding) domain.
Sequence caution	The sequence AAH32443.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	NuRD complex Non-traceable author statement. Source: BHF-UCL
Molecular function	DNA binding Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DDX5	P17844	4	EBI-1783068,EBI-351962

Alternative products

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

Isoform 1 (identifier: O95983-1)

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: O95983-2)

The sequence of this isoform differs from the canonical sequence as follows:
     5-36: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 291	291	Methyl-CpG-binding domain protein 3		PRO_0000096262
Regions
	Domain	1 – 72	72	MBD
	Coiled coil	216 – 245	30	Potential
	Compositional bias	272 – 281	10	Poly-Glu
Amino acid modifications
	Modified residue	4	1	N6-acetyllysine Ref.13
	Modified residue	56	1	Phosphoserine Ref.11 Ref.12
	Modified residue	109	1	N6-acetyllysine Ref.13
	Modified residue	141	1	N6-acetyllysine Ref.13
	Modified residue	144	1	Phosphoserine Ref.12
Natural variations
	Alternative sequence	5 – 36	32	Missing in isoform 2.		VSP_011081
Experimental info
	Mutagenesis	30	1	H → K: No effect. Confers strong binding to methylated CpG (in vitro); when associated with Y-30. Ref.8
	Mutagenesis	34	1	F → A: Augments DNA binding activity, irrespective of DNA methylation. Ref.8
	Mutagenesis	34	1	F → Y: Confers weak binding to methylated CpG (in vitro). Confers strong binding to methylated CpG (in vitro); when associated with K-30. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: B62134DD1BEB636B	FASTA	291	32,844
	10 20 30 40 50 60 MERKRWECPA LPQGWEREEV PRRSGLSAGH RDVFYYSPSG KKFRSKPQLA RYLGGSMDLS 70 80 90 100 110 120 TFDFRTGKML MSKMNKSRQR VRYDSSNQVK GKPDLNTALP VRQTASIFKQ PVTKITNHPS 130 140 150 160 170 180 NKVKSDPQKA VDQPRQLFWE KKLSGLNAFD IAEELVKTMD LPKGLQGVGP GCTDETLLSA 190 200 210 220 230 240 IASALHTSTM PITGQLSAAV EKNPGVWLNT TQPLCKAFMV TDEDIRKQEE LVQQVRKRLE 250 260 270 280 290 EALMADMLAH VEELARDGEA PLDKACAEDD DEEDEEEEEE EPDPDPEMEH V
	Isoform 2 [UniParc]. Checksum: 2578753C1E5D6A0B	FASTA	259	29,014
	10 20 30 40 50 60 MERKSPSGKK FRSKPQLARY LGGSMDLSTF DFRTGKMLMS KMNKSRQRVR YDSSNQVKGK 70 80 90 100 110 120 PDLNTALPVR QTASIFKQPV TKITNHPSNK VKSDPQKAVD QPRQLFWEKK LSGLNAFDIA 130 140 150 160 170 180 EELVKTMDLP KGLQGVGPGC TDETLLSAIA SALHTSTMPI TGQLSAAVEK NPGVWLNTTQ 190 200 210 220 230 240 PLCKAFMVTD EDIRKQEELV QQVRKRLEEA LMADMLAHVE ELARDGEAPL DKACAEDDDE 250 EDEEEEEEEP DPDPEMEHV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a family of mammalian methyl-CpG binding proteins." Hendrich B., Bird A. Mol. Cell. Biol. 18:6538-6547(1998) [PubMed: 9774669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain, Cervix, Muscle and Uterus.
[6]	"MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase." Tatematsu K., Yamazaki T., Ishikawa F. Genes Cells 5:677-688(2000) [PubMed: 10947852] [Abstract] Cited for: FUNCTION, HETERODIMERIZATION WITH MBD2, INTERACTION WITH DNMT1.
[7]	"Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1." Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., Howard B.H. J. Biol. Chem. 276:6817-6824(2001) [PubMed: 11102443] [Abstract] Cited for: INTERACTION WITH THE HDAC1 COMPLEX, MASS SPECTROMETRY.
[8]	"The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2." Saito M., Ishikawa F. J. Biol. Chem. 277:35434-35439(2002) [PubMed: 12124384] [Abstract] Cited for: FUNCTION, INTERACTION WITH HDAC1; MTA2 AND THE NURD COMPLEX, MUTAGENESIS OF HIS-30 AND PHE-34.
[9]	"Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3." Brackertz M., Boeke J., Zhang R., Renkawitz R. J. Biol. Chem. 277:40958-40966(2002) [PubMed: 12183469] [Abstract] Cited for: INTERACTION WITH P66ALPHA AND P66BETA.
[10]	"Identification and functional characterization of the p66/p68 components of the MeCP1 complex." Feng Q., Cao R., Xia L., Erdjument-Bromage H., Tempst P., Zhang Y. Mol. Cell. Biol. 22:536-546(2002) [PubMed: 11756549] [Abstract] Cited for: INTERACTION WITH P66BETA AND THE MECP1 COMPLEX.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-144, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-4; LYS-109 AND LYS-141, MASS SPECTROMETRY.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF072247 mRNA. Translation: AAC68876.1. AK290882 mRNA. Translation: BAF83571.1. AC005943 Genomic DNA. Translation: AAC72104.1. CH471139 Genomic DNA. Translation: EAW69477.1. CH471139 Genomic DNA. Translation: EAW69478.1. CH471139 Genomic DNA. Translation: EAW69481.1. BC009372 mRNA. Translation: AAH09372.1. BC009438 mRNA. Translation: AAH09438.1. BC032443 mRNA. Translation: AAH32443.1. Different initiation. BC043619 mRNA. Translation: AAH43619.1.
IPI	IPI00439194. IPI00439195.
RefSeq	NP_003917.1. NM_003926.5.
UniGene	Hs.178728.
3D structure databases
ProteinModelPortal	O95983.
SMR	O95983. Positions 2-69, 216-249.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95983. 10 interactions.
STRING	O95983.
PTM databases
PhosphoSite	O95983.
Proteomic databases
PRIDE	O95983.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000156825; ENSP00000156825; ENSG00000071655. ENST00000355664; ENSP00000347886; ENSG00000071655.
GeneID	53615.
KEGG	hsa:53615.
UCSC	uc002ltj.2. human. uc002ltk.2. human.
Organism-specific databases
CTD	53615.
GeneCards	GC19M001576.
H-InvDB	HIX0014590.
HGNC	HGNC:6918. MBD3.
HPA	CAB013265.
MIM	603573. gene.
neXtProt	NX_O95983.
PharmGKB	PA30661.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12869.
GeneTree	ENSGT00410000025376.
HOGENOM	HBG315648.
HOVERGEN	HBG052417.
InParanoid	O95983.
OMA	RQRMRYD.
OrthoDB	EOG4GF3FS.
PhylomeDB	O95983.
Enzyme and pathway databases
Pathway_Interaction_DB	hdac_classi_pathway. Signaling events mediated by HDAC Class I.
Gene expression databases
ArrayExpress	O95983.
Bgee	O95983.
CleanEx	HS_MBD3.
Genevestigator	O95983.
GermOnline	ENSG00000071655. Homo sapiens.
Family and domain databases
InterPro	IPR016177. DNA-bd_integrase-typ. IPR001739. Methyl_CpG_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.
KO	K11591.
Pfam	PF01429. MBD. 1 hit. [Graphical view]
SMART	SM00391. MBD. 1 hit. [Graphical view]
SUPFAM	SSF54171. DNA-binding_integrase-type. 1 hit.
PROSITE	PS50982. MBD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	56092.
SOURCE	Search...

Entry information

Entry name

MBD3_HUMAN

Accession

Primary (citable) accession number: O95983
Secondary accession number(s): A8K4B7 , D6W5Z2, Q6PIL9, Q6PJZ9, Q86XF4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.