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Methyl-CpG-binding protein 2 (MeCp-2 protein) (MeCp2)

 MECP2_RAT               Reviewed;         492 AA.
Q00566; Q09HV7; Q09HV8;
01-APR-1993, integrated into UniProtKB/Swiss-Prot.
01-APR-1993, sequence version 1.
22-NOV-2017, entry version 142.
RecName: Full=Methyl-CpG-binding protein 2;
Short=MeCp-2 protein;
Short=MeCp2;
Name=Mecp2;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND PARTIAL PROTEIN SEQUENCE.
STRAIN=Wistar; TISSUE=Brain, and Corpus striatum;
PubMed=1606614; DOI=10.1016/0092-8674(92)90610-O;
Lewis J.D., Meehan R.R., Henzel W.J., Maurer-Fogy I., Jeppesen P.,
Klein F., Bird A.;
"Purification, sequence, and cellular localization of a novel
chromosomal protein that binds to methylated DNA.";
Cell 69:905-914(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), SUBCELLULAR LOCATION,
AND INDUCTION BY FLUOXETINE AND COCAINE.
STRAIN=Wistar; TISSUE=Brain cortex;
PubMed=16670375; DOI=10.1124/mol.106.022301;
Cassel S., Carouge D., Gensburger C., Anglard P., Burgun C.,
Dietrich J.-B., Aunis D., Zwiller J.;
"Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1
in adult rat brain.";
Mol. Pharmacol. 70:487-492(2006).
[3]
PHOSPHORYLATION AT SER-80; SER-229 AND SER-421, AND IDENTIFICATION BY
MASS SPECTROMETRY.
PubMed=17046689; DOI=10.1016/j.neuron.2006.09.037;
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.;
"Brain-specific phosphorylation of MeCP2 regulates activity-dependent
Bdnf transcription, dendritic growth, and spine maturation.";
Neuron 52:255-269(2006).
[4]
INTERACTION WITH ATRX.
PubMed=17296936; DOI=10.1073/pnas.0608056104;
Nan X., Hou J., Maclean A., Nasir J., Lafuente M.J., Shu X.,
Kriaucionis S., Bird A.;
"Interaction between chromatin proteins MECP2 and ATRX is disrupted by
mutations that cause inherited mental retardation.";
Proc. Natl. Acad. Sci. U.S.A. 104:2709-2714(2007).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-80 AND SER-229,
AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22673903; DOI=10.1038/ncomms1871;
Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
Lundby C., Olsen J.V.;
"Quantitative maps of protein phosphorylation sites across 14
different rat organs and tissues.";
Nat. Commun. 3:876-876(2012).
-!- 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. Binds both 5-methylcytosine
(5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a
preference for 5-methylcytosine (5mC).
{ECO:0000250|UniProtKB:Q9Z2D6}.
-!- SUBUNIT: 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). Interacts with TBL1XR1;
bridges interaction between MECP2 and NCOR1. Interacts with TBL1X;
recuits TBL1X to the heterochromatin foci (By similarity).
{ECO:0000250|UniProtKB:P51608, ECO:0000250|UniProtKB:Q9Z2D6,
ECO:0000269|PubMed:17296936}.
-!- INTERACTION:
P46100:ATRX (xeno); NbExp=6; IntAct=EBI-9396907, EBI-396461;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16670375}.
Note=Colocalized with methyl-CpG in the genome. Colocalized with
TBL1X to the heterochromatin foci. {ECO:0000250|UniProtKB:P51608}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=A; Synonyms=e2;
IsoId=Q00566-1; Sequence=Displayed;
Name=B; Synonyms=e1;
IsoId=Q00566-2; Sequence=VSP_022950;
-!- TISSUE SPECIFICITY: Present in all adult somatic tissues tested.
-!- INDUCTION: In brain, by repeated injections of fluoxetine or
cocaine. {ECO:0000269|PubMed:16670375}.
-!- PTM: 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.
{ECO:0000269|PubMed:17046689}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; M94064; AAA41584.1; -; mRNA.
EMBL; DQ897368; ABI55237.1; -; mRNA.
EMBL; DQ897369; ABI55238.1; -; mRNA.
PIR; A41907; A41907.
RefSeq; NP_073164.2; NM_022673.2.
RefSeq; XP_006229629.1; XM_006229567.3.
UniGene; Rn.38416; -.
UniGene; Rn.9680; -.
ProteinModelPortal; Q00566; -.
SMR; Q00566; -.
BioGrid; 248038; 1.
CORUM; Q00566; -.
DIP; DIP-60875N; -.
IntAct; Q00566; 2.
STRING; 10116.ENSRNOP00000053166; -.
iPTMnet; Q00566; -.
PhosphoSitePlus; Q00566; -.
PaxDb; Q00566; -.
PRIDE; Q00566; -.
GeneID; 29386; -.
KEGG; rno:29386; -.
CTD; 4204; -.
RGD; 3075; Mecp2.
eggNOG; KOG4161; Eukaryota.
eggNOG; ENOG41126JX; LUCA.
HOGENOM; HOG000015809; -.
HOVERGEN; HBG052445; -.
InParanoid; Q00566; -.
KO; K11588; -.
PhylomeDB; Q00566; -.
TreeFam; TF332974; -.
PRO; PR:Q00566; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005737; C:cytoplasm; ISO:RGD.
GO; GO:0005829; C:cytosol; IDA:RGD.
GO; GO:0005615; C:extracellular space; ISO:RGD.
GO; GO:0000792; C:heterochromatin; ISO:RGD.
GO; GO:0005739; C:mitochondrion; IEA:GOC.
GO; GO:0000790; C:nuclear chromatin; IDA:RGD.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0098794; C:postsynapse; IEA:GOC.
GO; GO:0043234; C:protein complex; IDA:RGD.
GO; GO:0003682; F:chromatin binding; IDA:RGD.
GO; GO:0031490; F:chromatin DNA binding; IDA:RGD.
GO; GO:0001047; F:core promoter binding; IDA:RGD.
GO; GO:0003677; F:DNA binding; ISO:RGD.
GO; GO:0010385; F:double-stranded methylated DNA binding; IDA:RGD.
GO; GO:0019899; F:enzyme binding; IPI:RGD.
GO; GO:0000400; F:four-way junction DNA binding; IDA:RGD.
GO; GO:0042826; F:histone deacetylase binding; IPI:RGD.
GO; GO:0008327; F:methyl-CpG binding; IDA:RGD.
GO; GO:0003729; F:mRNA binding; ISO:RGD.
GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
GO; GO:0003723; F:RNA binding; ISO:RGD.
GO; GO:0035197; F:siRNA binding; ISO:RGD.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; ISO:RGD.
GO; GO:0008134; F:transcription factor binding; ISO:RGD.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISO:RGD.
GO; GO:0045322; F:unmethylated CpG binding; IDA:RGD.
GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
GO; GO:0001662; P:behavioral fear response; ISO:RGD.
GO; GO:0007420; P:brain development; ISO:RGD.
GO; GO:0032048; P:cardiolipin metabolic process; ISO:RGD.
GO; GO:0050432; P:catecholamine secretion; ISO:RGD.
GO; GO:0006576; P:cellular biogenic amine metabolic process; ISO:RGD.
GO; GO:0071317; P:cellular response to isoquinoline alkaloid; IDA:RGD.
GO; GO:0035865; P:cellular response to potassium ion; IDA:RGD.
GO; GO:0021549; P:cerebellum development; IEP:RGD.
GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
GO; GO:0006342; P:chromatin silencing; ISO:RGD.
GO; GO:0016358; P:dendrite development; ISO:RGD.
GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
GO; GO:0008211; P:glucocorticoid metabolic process; ISO:RGD.
GO; GO:0006541; P:glutamine metabolic process; ISO:RGD.
GO; GO:0007507; P:heart development; IEP:RGD.
GO; GO:0021766; P:hippocampus development; IEP:RGD.
GO; GO:0016573; P:histone acetylation; ISO:RGD.
GO; GO:0016571; P:histone methylation; ISO:RGD.
GO; GO:0006020; P:inositol metabolic process; ISO:RGD.
GO; GO:0007612; P:learning; ISO:RGD.
GO; GO:0007626; P:locomotory behavior; IBA:GO_Central.
GO; GO:0007616; P:long-term memory; ISO:RGD.
GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD.
GO; GO:0048286; P:lung alveolus development; IEP:RGD.
GO; GO:0007613; P:memory; ISO:RGD.
GO; GO:0006122; P:mitochondrial electron transport, ubiquinol to cytochrome c; ISO:RGD.
GO; GO:0007052; P:mitotic spindle organization; ISO:RGD.
GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD.
GO; GO:0048712; P:negative regulation of astrocyte differentiation; IDA:RGD.
GO; GO:1903860; P:negative regulation of dendrite extension; IMP:RGD.
GO; GO:0061000; P:negative regulation of dendritic spine development; IMP:RGD.
GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
GO; GO:0035067; P:negative regulation of histone acetylation; ISO:RGD.
GO; GO:0031061; P:negative regulation of histone methylation; ISO:RGD.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
GO; GO:2000635; P:negative regulation of primary miRNA processing; IMP:RGD.
GO; GO:0032091; P:negative regulation of protein binding; IMP:RGD.
GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; ISO:RGD.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:RGD.
GO; GO:2000820; P:negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation; ISO:RGD.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:RGD.
GO; GO:0001976; P:neurological system process involved in regulation of systemic arterial blood pressure; ISO:RGD.
GO; GO:0050905; P:neuromuscular process; ISO:RGD.
GO; GO:0050884; P:neuromuscular process controlling posture; ISO:RGD.
GO; GO:0030182; P:neuron differentiation; IEP:RGD.
GO; GO:0042551; P:neuron maturation; ISO:RGD.
GO; GO:0031175; P:neuron projection development; ISO:RGD.
GO; GO:0021772; P:olfactory bulb development; IEP:RGD.
GO; GO:0014003; P:oligodendrocyte development; IEP:RGD.
GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
GO; GO:0009405; P:pathogenesis; ISO:RGD.
GO; GO:0046470; P:phosphatidylcholine metabolic process; ISO:RGD.
GO; GO:1901953; P:positive regulation of anterograde dense core granule transport; IMP:RGD.
GO; GO:1905492; P:positive regulation of branching morphogenesis of a nerve; IMP:RGD.
GO; GO:0008284; P:positive regulation of cell proliferation; ISO:RGD.
GO; GO:1903861; P:positive regulation of dendrite extension; IMP:RGD.
GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:RGD.
GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:RGD.
GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
GO; GO:1900114; P:positive regulation of histone H3-K9 trimethylation; ISO:RGD.
GO; GO:0090063; P:positive regulation of microtubule nucleation; ISO:RGD.
GO; GO:1901956; P:positive regulation of retrograde dense core granule transport; IMP:RGD.
GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
GO; GO:0031915; P:positive regulation of synaptic plasticity; IMP:RGD.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
GO; GO:0009791; P:post-embryonic development; ISO:RGD.
GO; GO:0021740; P:principal sensory nucleus of trigeminal nerve development; IEP:RGD.
GO; GO:0019230; P:proprioception; ISO:RGD.
GO; GO:0008104; P:protein localization; ISO:RGD.
GO; GO:0044030; P:regulation of DNA methylation; IMP:RGD.
GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
GO; GO:0006349; P:regulation of gene expression by genetic imprinting; ISO:RGD.
GO; GO:0040029; P:regulation of gene expression, epigenetic; ISO:RGD.
GO; GO:0002087; P:regulation of respiratory gaseous exchange by neurological system process; ISO:RGD.
GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
GO; GO:0007585; P:respiratory gaseous exchange; ISO:RGD.
GO; GO:0042220; P:response to cocaine; IDA:RGD.
GO; GO:0032355; P:response to estradiol; IEP:RGD.
GO; GO:0001666; P:response to hypoxia; ISO:RGD.
GO; GO:0010212; P:response to ionizing radiation; IEP:RGD.
GO; GO:0010288; P:response to lead ion; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
GO; GO:0035176; P:social behavior; IMP:RGD.
GO; GO:0021510; P:spinal cord development; IEP:RGD.
GO; GO:0001964; P:startle response; ISO:RGD.
GO; GO:0021756; P:striatum development; IEP:RGD.
GO; GO:0007416; P:synapse assembly; ISO:RGD.
GO; GO:0021794; P:thalamus development; IEP:RGD.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0021591; P:ventricular system development; ISO:RGD.
GO; GO:0008542; P:visual learning; ISO:RGD.
InterPro; IPR016177; DNA-bd_dom_sf.
InterPro; IPR017353; Me_CpG-bd_MeCP2.
InterPro; IPR001739; Methyl_CpG_DNA-bd.
PANTHER; PTHR15074:SF4; PTHR15074:SF4; 1.
Pfam; PF01429; MBD; 1.
PIRSF; PIRSF038006; Methyl_CpG_bd_MeCP2; 1.
SMART; SM00391; MBD; 1.
SUPFAM; SSF54171; SSF54171; 1.
PROSITE; PS50982; MBD; 1.
1: Evidence at protein level;
Acetylation; Alternative splicing; Complete proteome;
Direct protein sequencing; DNA-binding; Methylation; Nucleus;
Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription;
Transcription regulation.
CHAIN 1 492 Methyl-CpG-binding protein 2.
/FTId=PRO_0000096348.
DOMAIN 90 162 MBD. {ECO:0000255|PROSITE-
ProRule:PRU00338}.
DNA_BIND 185 197 A.T hook 1.
DNA_BIND 265 277 A.T hook 2.
REGION 269 309 Interaction with NCOR2.
{ECO:0000250|UniProtKB:Q9Z2D6}.
REGION 285 309 Interaction with TBL1XR1.
{ECO:0000250|UniProtKB:Q9Z2D6}.
COMPBIAS 366 372 His-rich.
COMPBIAS 379 403 Pro-rich.
MOD_RES 13 13 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 80 80 Phosphoserine.
{ECO:0000244|PubMed:22673903,
ECO:0000269|PubMed:17046689}.
MOD_RES 116 116 Phosphoserine.
{ECO:0000250|UniProtKB:P51608}.
MOD_RES 162 162 Omega-N-methylarginine.
{ECO:0000250|UniProtKB:Q9Z2D6}.
MOD_RES 216 216 Phosphoserine.
{ECO:0000250|UniProtKB:P51608}.
MOD_RES 229 229 Phosphoserine.
{ECO:0000244|PubMed:22673903,
ECO:0000269|PubMed:17046689}.
MOD_RES 321 321 N6-acetyllysine.
{ECO:0000250|UniProtKB:Q9Z2D6}.
MOD_RES 421 421 Phosphoserine; by CaMK2.
{ECO:0000269|PubMed:17046689}.
MOD_RES 424 424 Phosphoserine.
{ECO:0000250|UniProtKB:P51608}.
MOD_RES 455 455 N6-acetyllysine.
{ECO:0000250|UniProtKB:P51608}.
VAR_SEQ 1 10 MVAGMLGLRK -> MAAAAAAAAAAAAAAAAAAAAAAAAPS
GGGGGEEERLE (in isoform B).
{ECO:0000303|PubMed:16670375}.
/FTId=VSP_022950.
CONFLICT 10 10 K -> E (in Ref. 2; ABI55238).
{ECO:0000305}.
SEQUENCE 492 AA; 53047 MW; A67E705C68BA2D38 CRC64;
MVAGMLGLRK EKSEDQDLQG LKEKPLKFKK VKKDKKEDKE GKHEPLQPSA HHSAEPAEAG
KAETSESSGS APAVPEASAS PKQRRSIIRD RGPMYDDPTL PEGWTRKLKQ RKSGRSAGKY
DVYLINPQGK AFRSKVELIA YFEKVGDTSL DPNDFDFTVT GRGSPSRREQ KPPKKPKSPK
APGTGRGRGR PKGSGTGRPK AAASEGVQVK RVLEKSPGKL LVKMPFQASP GGKGEGGGAT
TSAQVMVIKR PGRKRKAEAD PQAIPKKRGR KPGSVVAAAA AEAKKKAVKE SSIRSVQETV
LPIKKRKTRE TVSIEVKEVV KPLLVSTLGE KSGKGLKTCK SPGRKSKESS PKGRSSSASS
PPKKEHHHHH HHAESPKAPM PLLPPPPPPE PQSSEDPISP PEPQDLSSSI CKEEKMPRAG
SLESDGCPKE PAKTQPMVAA AATTTTTTTT TVAEKYKHRG EGERKDIVSS SMPRPNREEP
VDSRTPVTER VS


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