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Q00566

- MECP2_RAT

UniProt

Q00566 - MECP2_RAT

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
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 1 (01 Apr 1993)
      Previous versions | rss
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    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

    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

    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

    MVAGMLGLRK EKSEDQDLQG LKEKPLKFKK VKKDKKEDKE GKHEPLQPSA    50
    HHSAEPAEAG KAETSESSGS APAVPEASAS PKQRRSIIRD RGPMYDDPTL 100
    PEGWTRKLKQ RKSGRSAGKY DVYLINPQGK AFRSKVELIA YFEKVGDTSL 150
    DPNDFDFTVT GRGSPSRREQ KPPKKPKSPK APGTGRGRGR PKGSGTGRPK 200
    AAASEGVQVK RVLEKSPGKL LVKMPFQASP GGKGEGGGAT TSAQVMVIKR 250
    PGRKRKAEAD PQAIPKKRGR KPGSVVAAAA AEAKKKAVKE SSIRSVQETV 300
    LPIKKRKTRE TVSIEVKEVV KPLLVSTLGE KSGKGLKTCK SPGRKSKESS 350
    PKGRSSSASS PPKKEHHHHH HHAESPKAPM PLLPPPPPPE PQSSEDPISP 400
    PEPQDLSSSI CKEEKMPRAG SLESDGCPKE PAKTQPMVAA AATTTTTTTT 450
    TVAEKYKHRG EGERKDIVSS SMPRPNREEP VDSRTPVTER VS 492
    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:
    EMBL
    GenBank
    DDBJ
    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_006229566.1.
    XP_006229629.1. XM_006229567.1.
    XP_006229630.1. XM_006229568.1.
    UniGeneiRn.38416.
    Rn.9680.

    Genome annotation databases

    GeneIDi29386.
    KEGGirno:29386.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_006229566.1.
    XP_006229629.1. XM_006229567.1.
    XP_006229630.1. XM_006229568.1.
    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 1, 2014
    This is version 117 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