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Q00566

- MECP2_RAT

UniProt

Q00566 - MECP2_RAT

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Protein

Methyl-CpG-binding protein 2

Gene

Mecp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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).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

  1. chromatin DNA binding Source: RGD
  2. double-stranded methylated DNA binding Source: RGD
  3. enzyme binding Source: RGD
  4. four-way junction DNA binding Source: RGD
  5. methyl-CpG binding Source: RGD
  6. unmethylated CpG binding Source: RGD

GO - Biological processi

  1. negative regulation of transcription, DNA-templated Source: RGD
  2. negative regulation of transcription from RNA polymerase II promoter Source: RGD
  3. 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: Unplaced

Organism-specific databases

RGDi3075. Mecp2.

Subcellular locationi

Nucleus 1 Publication
Note: Colocalized with methyl-CpG in the genome.

GO - Cellular componenti

  1. cytosol Source: RGD
  2. nuclear chromatin Source: RGD
  3. nucleus Source: RGD
  4. 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, CDKL5 and ATRX.1 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

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. Align

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 .
PIRi A41907.
RefSeqi NP_073164.2. NM_022673.2.
XP_006229628.1. XM_006229566.2.
XP_006229629.1. XM_006229567.2.
UniGenei Rn.38416.
Rn.9680.

3D structure databases

ProteinModelPortali Q00566.
SMRi Q00566. Positions 71-195.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248038. 1 interaction.
DIPi DIP-60875N.

PTM databases

PhosphoSitei Q00566.

Proteomic databases

PaxDbi Q00566.
PRIDEi Q00566.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 29386.
KEGGi rno:29386.

Organism-specific databases

CTDi 4204.
RGDi 3075. Mecp2.

Phylogenomic databases

eggNOGi NOG237320.
HOGENOMi HOG000015809.
HOVERGENi HBG052445.
InParanoidi Q00566.
KOi K11588.
PhylomeDBi Q00566.
TreeFami TF332974.

Miscellaneous databases

NextBioi 608987.
PROi Q00566.

Gene expression databases

Genevestigatori Q00566.

Family and domain databases

Gene3Di 3.30.890.10. 1 hit.
InterProi IPR017956. AT_hook_DNA-bd_motif.
IPR016177. DNA-bd_dom.
IPR017353. Me_CpG-bd_MeCP2.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view ]
Pfami PF01429. MBD. 1 hit.
[Graphical view ]
PIRSFi PIRSF038006. Methyl_CpG_bd_MeCP2. 1 hit.
SMARTi SM00384. AT_hook. 2 hits.
SM00391. MBD. 1 hit.
[Graphical view ]
SUPFAMi SSF54171. SSF54171. 1 hit.
PROSITEi PS50982. MBD. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 118 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