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Protein

Methyl-CpG-binding protein 2

Gene

Mecp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi185 – 19713A.T hook 1Add
BLAST
DNA bindingi265 – 27713A.T hook 2Add
BLAST

GO - Molecular functioni

  • chromatin DNA binding Source: RGD
  • double-stranded methylated DNA binding Source: RGD
  • enzyme binding Source: RGD
  • four-way junction DNA binding Source: RGD
  • histone deacetylase binding Source: RGD
  • methyl-CpG binding Source: RGD
  • unmethylated CpG binding Source: RGD

GO - Biological processi

  • heart development Source: RGD
  • locomotory behavior Source: GO_Central
  • negative regulation of astrocyte differentiation Source: RGD
  • negative regulation of transcription, DNA-templated Source: RGD
  • negative regulation of transcription from RNA polymerase II promoter Source: RGD
  • regulation of DNA methylation Source: RGD
  • response to estradiol Source: RGD
  • response to ionizing radiation Source: RGD
  • response to lead ion Source: RGD
  • response to organic cyclic compound Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Methyl-CpG-binding protein 2
Short name:
MeCp-2 protein
Short name:
MeCp2
Gene namesi
Name:Mecp2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3075. Mecp2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
  • heterochromatin Source: GO_Central
  • nuclear chromatin Source: RGD
  • nucleus Source: RGD
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 492492Methyl-CpG-binding protein 2PRO_0000096348Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei80 – 801Phosphoserine1 Publication
Modified residuei116 – 1161PhosphoserineBy similarity
Modified residuei216 – 2161PhosphoserineBy similarity
Modified residuei229 – 2291Phosphoserine1 Publication
Modified residuei321 – 3211N6-acetyllysineBy similarity
Modified residuei421 – 4211Phosphoserine; by CaMK21 Publication
Modified residuei424 – 4241PhosphoserineBy similarity
Modified residuei455 – 4551N6-acetyllysineBy similarity

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ00566.
PRIDEiQ00566.

PTM databases

PhosphoSiteiQ00566.

Expressioni

Tissue specificityi

Present in all adult somatic tissues tested.

Inductioni

In brain, by repeated injections of fluoxetine or cocaine.1 Publication

Gene expression databases

GenevestigatoriQ00566.

Interactioni

Subunit structurei

Interacts with FNBP3 (By similarity). Interacts with CDKL5 (By similarity). Interacts with ATRX; MECP2 recruits ATRX to pericentric heterochromatin in neuronal cells (PubMed:17296936). Interacts with NCOR2 (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi248038. 1 interaction.
DIPiDIP-60875N.

Structurei

3D structure databases

ProteinModelPortaliQ00566.
SMRiQ00566. Positions 71-195.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini90 – 16273MBDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni269 – 30941Interaction with NCOR2By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi366 – 3727His-rich
Compositional biasi379 – 40325Pro-richAdd
BLAST

Sequence similaritiesi

Contains 2 A.T hook DNA-binding domains.Curated
Contains 1 MBD (methyl-CpG-binding) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG237320.
HOGENOMiHOG000015809.
HOVERGENiHBG052445.
InParanoidiQ00566.
KOiK11588.
PhylomeDBiQ00566.
TreeFamiTF332974.

Family and domain databases

Gene3Di3.30.890.10. 1 hit.
InterProiIPR017956. AT_hook_DNA-bd_motif.
IPR016177. DNA-bd_dom.
IPR017353. Me_CpG-bd_MeCP2.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamiPF01429. MBD. 1 hit.
[Graphical view]
PIRSFiPIRSF038006. Methyl_CpG_bd_MeCP2. 1 hit.
SMARTiSM00384. AT_hook. 2 hits.
SM00391. MBD. 1 hit.
[Graphical view]
SUPFAMiSSF54171. SSF54171. 1 hit.
PROSITEiPS50982. MBD. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: Q00566-1) [UniParc]FASTAAdd to basket

Also known as: e2

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.

« Hide

        10         20         30         40         50
MVAGMLGLRK EKSEDQDLQG LKEKPLKFKK VKKDKKEDKE GKHEPLQPSA
60 70 80 90 100
HHSAEPAEAG KAETSESSGS APAVPEASAS PKQRRSIIRD RGPMYDDPTL
110 120 130 140 150
PEGWTRKLKQ RKSGRSAGKY DVYLINPQGK AFRSKVELIA YFEKVGDTSL
160 170 180 190 200
DPNDFDFTVT GRGSPSRREQ KPPKKPKSPK APGTGRGRGR PKGSGTGRPK
210 220 230 240 250
AAASEGVQVK RVLEKSPGKL LVKMPFQASP GGKGEGGGAT TSAQVMVIKR
260 270 280 290 300
PGRKRKAEAD PQAIPKKRGR KPGSVVAAAA AEAKKKAVKE SSIRSVQETV
310 320 330 340 350
LPIKKRKTRE TVSIEVKEVV KPLLVSTLGE KSGKGLKTCK SPGRKSKESS
360 370 380 390 400
PKGRSSSASS PPKKEHHHHH HHAESPKAPM PLLPPPPPPE PQSSEDPISP
410 420 430 440 450
PEPQDLSSSI CKEEKMPRAG SLESDGCPKE PAKTQPMVAA AATTTTTTTT
460 470 480 490
TVAEKYKHRG EGERKDIVSS SMPRPNREEP VDSRTPVTER VS
Length:492
Mass (Da):53,047
Last modified:April 1, 1993 - v1
Checksum:iA67E705C68BA2D38
GO
Isoform B (identifier: Q00566-2) [UniParc]FASTAAdd to basket

Also known as: e1

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MVAGMLGLRK → MAAAAAAAAAAAAAAAAAAAAAAAAPSGGGGGEEERLE

Show »
Length:520
Mass (Da):55,082
Checksum:i02800646B6DF90D8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 101K → E in ABI55238 (PubMed:16670375).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1010MVAGMLGLRK → MAAAAAAAAAAAAAAAAAAA AAAAAPSGGGGGEEERLE in isoform B. 1 PublicationVSP_022950

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94064 mRNA. Translation: AAA41584.1.
DQ897368 mRNA. Translation: ABI55237.1.
DQ897369 mRNA. Translation: ABI55238.1.
PIRiA41907.
RefSeqiNP_073164.2. NM_022673.2.
XP_006229628.1. XM_006229566.2.
XP_006229629.1. XM_006229567.2.
UniGeneiRn.38416.
Rn.9680.

Genome annotation databases

GeneIDi29386.
KEGGirno:29386.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94064 mRNA. Translation: AAA41584.1.
DQ897368 mRNA. Translation: ABI55237.1.
DQ897369 mRNA. Translation: ABI55238.1.
PIRiA41907.
RefSeqiNP_073164.2. NM_022673.2.
XP_006229628.1. XM_006229566.2.
XP_006229629.1. XM_006229567.2.
UniGeneiRn.38416.
Rn.9680.

3D structure databases

ProteinModelPortaliQ00566.
SMRiQ00566. Positions 71-195.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248038. 1 interaction.
DIPiDIP-60875N.

PTM databases

PhosphoSiteiQ00566.

Proteomic databases

PaxDbiQ00566.
PRIDEiQ00566.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29386.
KEGGirno:29386.

Organism-specific databases

CTDi4204.
RGDi3075. Mecp2.

Phylogenomic databases

eggNOGiNOG237320.
HOGENOMiHOG000015809.
HOVERGENiHBG052445.
InParanoidiQ00566.
KOiK11588.
PhylomeDBiQ00566.
TreeFamiTF332974.

Miscellaneous databases

NextBioi608987.
PROiQ00566.

Gene expression databases

GenevestigatoriQ00566.

Family and domain databases

Gene3Di3.30.890.10. 1 hit.
InterProiIPR017956. AT_hook_DNA-bd_motif.
IPR016177. DNA-bd_dom.
IPR017353. Me_CpG-bd_MeCP2.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamiPF01429. MBD. 1 hit.
[Graphical view]
PIRSFiPIRSF038006. Methyl_CpG_bd_MeCP2. 1 hit.
SMARTiSM00384. AT_hook. 2 hits.
SM00391. MBD. 1 hit.
[Graphical view]
SUPFAMiSSF54171. SSF54171. 1 hit.
PROSITEiPS50982. MBD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA."
    Lewis J.D., Meehan R.R., Henzel W.J., Maurer-Fogy I., Jeppesen P., Klein F., Bird A.
    Cell 69:905-914(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), PARTIAL PROTEIN SEQUENCE.
    Strain: Wistar.
    Tissue: Brain and Corpus striatum.
  2. "Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain."
    Cassel S., Carouge D., Gensburger C., Anglard P., Burgun C., Dietrich J.-B., Aunis D., Zwiller J.
    Mol. Pharmacol. 70:487-492(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), SUBCELLULAR LOCATION, INDUCTION BY FLUOXETINE AND COCAINE.
    Strain: Wistar.
    Tissue: Brain cortex.
  3. "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] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-80; SER-229 AND SER-421, IDENTIFICATION BY MASS SPECTROMETRY.
  4. "Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation."
    Nan X., Hou J., Maclean A., Nasir J., Lafuente M.J., Shu X., Kriaucionis S., Bird A.
    Proc. Natl. Acad. Sci. U.S.A. 104:2709-2714(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATRX.

Entry informationi

Entry nameiMECP2_RAT
AccessioniPrimary (citable) accession number: Q00566
Secondary accession number(s): Q09HV7, Q09HV8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: May 27, 2015
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.