Q9Z2D6 (MECP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methyl-CpG-binding protein 2
Short name=MeCp-2 protein
Short name=MeCp2

Gene names

Name:

Mecp2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	484 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A By similarity.
Subunit structure	Interacts with CDKL5 By similarity. Interacts with FNBP3. Ref.7
Subcellular location	Nucleus. Note: Colocalized with methyl-CpG in the genome. Ref.8
Post-translational modification	Phosphorylated on Ser-421 by CaMK2 in brain upon synaptic activity, which attenuates its repressor activity and seems to regulate dendritic growth and spine maturation. Does not seem to be phosphorylated on Ser-421 in other tissues. Ref.9 Ref.10 Ref.11
Sequence similarities	Contains 2 A.T hook DNA-binding domains. Contains 1 MBD (methyl-CpG-binding) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	DNA-binding
Molecular function	Repressor
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adult locomotory behavior Inferred from mutant phenotype. Source: MGI behavioral fear response Inferred from mutant phenotype. Source: MGI cardiolipin metabolic process Inferred from mutant phenotype. Source: MGI catecholamine secretion Inferred from mutant phenotype. Source: MGI cerebellum development Inferred from mutant phenotype. Source: MGI chromatin silencing Inferred from mutant phenotype. Source: MGI dendrite development Inferred from mutant phenotype. Source: MGI embryo development Inferred from mutant phenotype. Source: MGI glucocorticoid metabolic process Inferred from mutant phenotype. Source: MGI glutamine metabolic process Inferred from mutant phenotype. Source: MGI histone acetylation Inferred from mutant phenotype. Source: MGI histone methylation Inferred from mutant phenotype. Source: MGI inositol metabolic process Inferred from mutant phenotype. Source: MGI long-term memory Inferred from mutant phenotype. Source: MGI long-term synaptic potentiation Inferred from mutant phenotype. Source: MGI mitochondrial electron transport, ubiquinol to cytochrome c Inferred from mutant phenotype. Source: MGI negative regulation of histone acetylation Inferred from mutant phenotype. Source: MGI negative regulation of histone methylation Inferred from mutant phenotype. Source: MGI negative regulation of neuron apoptosis Inferred from mutant phenotype. Source: MGI neurological system process involved in regulation of systemic arterial blood pressure Inferred from mutant phenotype. Source: MGI neuron maturation Inferred from mutant phenotype. Source: MGI pathogenesis Inferred from mutant phenotype. Source: MGI phosphatidylcholine metabolic process Inferred from mutant phenotype. Source: MGI positive regulation of cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of synapse assembly Inferred from mutant phenotype. Source: MGI positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: MGI post-embryonic development Inferred from mutant phenotype. Source: MGI proprioception Inferred from mutant phenotype. Source: MGI protein localization Inferred from mutant phenotype. Source: MGI regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype. Source: MGI regulation of gene expression by genetic imprinting Inferred from mutant phenotype. Source: MGI regulation of respiratory gaseous exchange by neurological system process Inferred from mutant phenotype. Source: MGI respiratory gaseous exchange Inferred from mutant phenotype. Source: MGI response to hypoxia Inferred from mutant phenotype. Source: MGI sensory perception of pain Inferred from mutant phenotype. Source: MGI social behavior Inferred from mutant phenotype. Source: MGI startle response Inferred from mutant phenotype. Source: MGI synapse assembly Inferred from mutant phenotype. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ventricular system development Inferred from mutant phenotype. Source: MGI visual learning Inferred from mutant phenotype. Source: MGI
Cellular component	cytosol Inferred from direct assay. Source: MGI heterochromatin Inferred from direct assay. Source: MGI nucleus Inferred from direct assay Ref.8. Source: MGI
Molecular function	chromatin binding Inferred from direct assay. Source: MGI double-stranded methylated DNA binding Inferred from direct assay. Source: MGI mRNA binding Inferred from direct assay. Source: MGI methyl-CpG binding Inferred from direct assay. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from direct assay. Source: MGI siRNA binding Inferred from direct assay. Source: MGI transcription factor binding Inferred from physical interaction. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Smarca2	O35846	2	EBI-1188816,EBI-371564

Alternative products

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

Isoform A (identifier: Q9Z2D6-1)

Also known as: Beta;

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 B (identifier: Q9Z2D6-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MVAGMLGLR → MAAAAATAAAAAAPSGGGGGGEEERL

Note: Ten times higher expression levels than isoform A in brain (at protein level).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 484	484	Methyl-CpG-binding protein 2		PRO_0000096347
Regions
	Domain	90 – 162	73	MBD
	DNA binding	185 – 197	13	A.T hook 1
	DNA binding	265 – 277	13	A.T hook 2
	Compositional bias	366 – 372	7	His-rich
	Compositional bias	379 – 403	25	Pro-rich
Amino acid modifications
	Modified residue	80	1	Phosphoserine Ref.10 Ref.11
	Modified residue	116	1	Phosphoserine By similarity
	Modified residue	229	1	Phosphoserine By similarity
	Modified residue	421	1	Phosphoserine; by CaMK2 Ref.9
	Modified residue	424	1	Phosphoserine By similarity
	Modified residue	447	1	N6-acetyllysine By similarity
Natural variations
	Alternative sequence	1 – 9	9	MVAGMLGLR → MAAAAATAAAAAAPSGGGGG GEEERL in isoform B.		VSP_022949
Experimental info
	Sequence conflict	328	1	L → P in BAE34602. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (Beta) [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 62FD228F0118A49F	FASTA	484	52,307
	10 20 30 40 50 60 MVAGMLGLRE EKSEDQDLQG LRDKPLKFKK AKKDKKEDKE GKHEPLQPSA HHSAEPAEAG 70 80 90 100 110 120 KAETSESSGS APAVPEASAS PKQRRSIIRD RGPMYDDPTL PEGWTRKLKQ RKSGRSAGKY 130 140 150 160 170 180 DVYLINPQGK AFRSKVELIA YFEKVGDTSL DPNDFDFTVT GRGSPSRREQ KPPKKPKSPK 190 200 210 220 230 240 APGTGRGRGR PKGSGTGRPK AAASEGVQVK RVLEKSPGKL VVKMPFQASP GGKGEGGGAT 250 260 270 280 290 300 TSAQVMVIKR PGRKRKAEAD PQAIPKKRGR KPGSVVAAAA AEAKKKAVKE SSIRSVHETV 310 320 330 340 350 360 LPIKKRKTRE TVSIEVKEVV KPLLVSTLGE KSGKGLKTCK SPGRKSKESS PKGRSSSASS 370 380 390 400 410 420 PPKKEHHHHH HHSESTKAPM PLLPSPPPPE PESSEDPISP PEPQDLSSSI CKEEKMPRGG 430 440 450 460 470 480 SLESDGCPKE PAKTQPMVAT TTTVAEKYKH RGEGERKDIV SSSMPRPNRE EPVDSRTPVT ERVS
	Isoform B (Alpha) [UniParc]. Checksum: E88FC12C21F95F4C	FASTA	501	53,576
	10 20 30 40 50 60 MAAAAATAAA AAAPSGGGGG GEEERLEEKS EDQDLQGLRD KPLKFKKAKK DKKEDKEGKH 70 80 90 100 110 120 EPLQPSAHHS AEPAEAGKAE TSESSGSAPA VPEASASPKQ RRSIIRDRGP MYDDPTLPEG 130 140 150 160 170 180 WTRKLKQRKS GRSAGKYDVY LINPQGKAFR SKVELIAYFE KVGDTSLDPN DFDFTVTGRG 190 200 210 220 230 240 SPSRREQKPP KKPKSPKAPG TGRGRGRPKG SGTGRPKAAA SEGVQVKRVL EKSPGKLVVK 250 260 270 280 290 300 MPFQASPGGK GEGGGATTSA QVMVIKRPGR KRKAEADPQA IPKKRGRKPG SVVAAAAAEA 310 320 330 340 350 360 KKKAVKESSI RSVHETVLPI KKRKTRETVS IEVKEVVKPL LVSTLGEKSG KGLKTCKSPG 370 380 390 400 410 420 RKSKESSPKG RSSSASSPPK KEHHHHHHHS ESTKAPMPLL PSPPPPEPES SEDPISPPEP 430 440 450 460 470 480 QDLSSSICKE EKMPRGGSLE SDGCPKEPAK TQPMVATTTT VAEKYKHRGE GERKDIVSSS 490 500 MPRPNREEPV DSRTPVTERV S

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 A). Strain: C57BL/6.
[2]	"A complex pattern of evolutionary conservation and alternative polyadenylation within the long 3'-untranslated region of the methyl-CpG-binding protein 2 gene (MeCP2) suggests a regulatory role in gene expression." Coy J.F., Sedlacek Z., Baechner D., Delius H., Poustka A. Hum. Mol. Genet. 8:1253-1262(1999) [PubMed: 10369871] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM A).
[3]	"Comparative analysis of the methyl CpG binding protein 2 locus in man and mouse reveals new untranslated sequences." Reichwald K., Thiessen J., Wiehe T., Kioschis P., Straetling W.H., Rosenthal A., Platzer M. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM A).
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Strain: C57BL/6J. Tissue: Visual cortex.
[5]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[6]	"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 A). Strain: FVB/N. Tissue: Mammary gland.
[7]	"FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich ligands." Bedford M.T., Chan D.C., Leder P. EMBO J. 16:2376-2383(1997) [PubMed: 9171351] [Abstract] Cited for: INTERACTION WITH FNBP3.
[8]	"The major form of MeCP2 has a novel N-terminus generated by alternative splicing." Kriaucionis S., Bird A. Nucleic Acids Res. 32:1818-1823(2004) [PubMed: 15034150] [Abstract] Cited for: IDENTIFICATION (ISOFORM B), SUBCELLULAR LOCATION.
[9]	"Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation." Zhou Z., Hong E.J., Cohen S., Zhao W.-N., Ho H.H., Schmidt L., Chen W.G., Lin Y., Savner E., Griffith E.C., Hu L., Steen J.A.J., Weitz C.J., Greenberg M.E. Neuron 52:255-269(2006) [PubMed: 17046689] [Abstract] Cited for: PHOSPHORYLATION AT SER-421.
[10]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed: 17203969] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF072251 mRNA. Translation: AAC68880.1. AJ132922 mRNA. Translation: CAB46495.1. AF121351 Genomic DNA. No translation available. AF158181 mRNA. Translation: AAF33024.1. AK158664 mRNA. Translation: BAE34602.1. AL672002 Genomic DNA. Translation: CAM18741.1. AL672002 Genomic DNA. Translation: CAM18742.1. BC027153 mRNA. Translation: AAH27153.1.
IPI	IPI00131063. IPI00775806.
RefSeq	NP_001075448.1. NM_001081979.1. NP_034918.1. NM_010788.3.
UniGene	Mm.131408. Mm.414303.
3D structure databases
ProteinModelPortal	Q9Z2D6.
SMR	Q9Z2D6. Positions 71-195.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Z2D6. 3 interactions.
MINT	MINT-225556.
STRING	Q9Z2D6.
PTM databases
PhosphoSite	Q9Z2D6.
Proteomic databases
PRIDE	Q9Z2D6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033770; ENSMUSP00000033770; ENSMUSG00000031393. ENSMUST00000100750; ENSMUSP00000098314; ENSMUSG00000031393. ENSMUST00000170481; ENSMUSP00000127115; ENSMUSG00000031393.
GeneID	17257.
KEGG	mmu:17257.
UCSC	uc009tnt.1. mouse. uc009tnu.1. mouse.
Organism-specific databases
CTD	4204.
MGI	MGI:99918. Mecp2.
Phylogenomic databases
eggNOG	roNOG14533.
GeneTree	ENSGT00530000063687.
HOVERGEN	HBG052445.
OMA	HHSEPPK.
PhylomeDB	Q9Z2D6.
Gene expression databases
ArrayExpress	Q9Z2D6.
Bgee	Q9Z2D6.
CleanEx	MM_MECP2.
Genevestigator	Q9Z2D6.
GermOnline	ENSMUSG00000031393. Mus musculus.
Family and domain databases
InterPro	IPR017956. AT_hook_DNA-bd_motif. IPR016177. DNA-bd_integrase-typ. IPR017353. Me_CpG-bd_MeCP2. IPR001739. Methyl_CpG_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.
KO	K11588.
Pfam	PF01429. MBD. 1 hit. [Graphical view]
PIRSF	PIRSF038006. Methyl_CpG_bd_MeCP2. 1 hit.
SMART	SM00384. AT_hook. 2 hits. 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	291736.
SOURCE	Search...

Entry information

Entry name

MECP2_MOUSE

Accession

Primary (citable) accession number: Q9Z2D6
Secondary accession number(s): B1AUZ2, B1AUZ3, Q3TYG1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	May 1, 1999
Last modified:	November 16, 2011
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program