MECP2_RAT
ID MECP2_RAT Reviewed; 492 AA.
AC Q00566; Q09HV7; Q09HV8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Methyl-CpG-binding protein 2;
DE Short=MeCp-2 protein;
DE Short=MeCp2;
GN Name=Mecp2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Wistar; TISSUE=Brain, and Corpus striatum;
RX PubMed=1606614; DOI=10.1016/0092-8674(92)90610-o;
RA Lewis J.D., Meehan R.R., Henzel W.J., Maurer-Fogy I., Jeppesen P.,
RA Klein F., Bird A.;
RT "Purification, sequence, and cellular localization of a novel chromosomal
RT protein that binds to methylated DNA.";
RL Cell 69:905-914(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), SUBCELLULAR LOCATION, AND
RP INDUCTION BY FLUOXETINE AND COCAINE.
RC STRAIN=Wistar; TISSUE=Brain cortex;
RX PubMed=16670375; DOI=10.1124/mol.106.022301;
RA Cassel S., Carouge D., Gensburger C., Anglard P., Burgun C.,
RA Dietrich J.-B., Aunis D., Zwiller J.;
RT "Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in
RT adult rat brain.";
RL Mol. Pharmacol. 70:487-492(2006).
RN [3]
RP PHOSPHORYLATION AT SER-80; SER-229 AND SER-421, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=17046689; DOI=10.1016/j.neuron.2006.09.037;
RA Zhou Z., Hong E.J., Cohen S., Zhao W.-N., Ho H.H., Schmidt L., Chen W.G.,
RA Lin Y., Savner E., Griffith E.C., Hu L., Steen J.A.J., Weitz C.J.,
RA Greenberg M.E.;
RT "Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf
RT transcription, dendritic growth, and spine maturation.";
RL Neuron 52:255-269(2006).
RN [4]
RP INTERACTION WITH ATRX.
RX PubMed=17296936; DOI=10.1073/pnas.0608056104;
RA Nan X., Hou J., Maclean A., Nasir J., Lafuente M.J., Shu X.,
RA Kriaucionis S., Bird A.;
RT "Interaction between chromatin proteins MECP2 and ATRX is disrupted by
RT mutations that cause inherited mental retardation.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2709-2714(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-80 AND SER-229, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Chromosomal protein that binds to methylated DNA. It can bind
CC specifically to a single methyl-CpG pair. It is not influenced by
CC sequences flanking the methyl-CpGs. Mediates transcriptional repression
CC through interaction with histone deacetylase and the corepressor SIN3A.
CC Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-
CC containing DNA, with a preference for 5-methylcytosine (5mC).
CC {ECO:0000250|UniProtKB:Q9Z2D6}.
CC -!- SUBUNIT: Interacts with FNBP3 (By similarity). Interacts with CDKL5 (By
CC similarity). Interacts with ATRX; MECP2 recruits ATRX to pericentric
CC heterochromatin in neuronal cells (PubMed:17296936). Interacts with
CC NCOR2 (By similarity). Interacts with TBL1XR1; bridges interaction
CC between MECP2 and NCOR1. Interacts with TBL1X; recruits TBL1X to the
CC heterochromatin foci (By similarity). {ECO:0000250|UniProtKB:P51608,
CC ECO:0000250|UniProtKB:Q9Z2D6, ECO:0000269|PubMed:17296936}.
CC -!- INTERACTION:
CC Q00566; P46100: ATRX; Xeno; NbExp=5; IntAct=EBI-9396907, EBI-396461;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16670375}.
CC Note=Colocalized with methyl-CpG in the genome. Colocalized with TBL1X
CC to the heterochromatin foci. {ECO:0000250|UniProtKB:P51608}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A; Synonyms=e2;
CC IsoId=Q00566-1; Sequence=Displayed;
CC Name=B; Synonyms=e1;
CC IsoId=Q00566-2; Sequence=VSP_022950;
CC -!- TISSUE SPECIFICITY: Present in all adult somatic tissues tested.
CC -!- INDUCTION: In brain, by repeated injections of fluoxetine or cocaine.
CC {ECO:0000269|PubMed:16670375}.
CC -!- PTM: Phosphorylated on Ser-421 by CaMK2 in brain upon synaptic
CC activity, which attenuates its repressor activity and seems to regulate
CC dendritic growth and spine maturation. {ECO:0000269|PubMed:17046689}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M94064; AAA41584.1; -; mRNA.
DR EMBL; DQ897368; ABI55237.1; -; mRNA.
DR EMBL; DQ897369; ABI55238.1; -; mRNA.
DR PIR; A41907; A41907.
DR RefSeq; NP_073164.2; NM_022673.2.
DR RefSeq; XP_006229629.1; XM_006229567.3.
DR AlphaFoldDB; Q00566; -.
DR BMRB; Q00566; -.
DR SMR; Q00566; -.
DR BioGRID; 248038; 3.
DR CORUM; Q00566; -.
DR DIP; DIP-60875N; -.
DR IntAct; Q00566; 3.
DR MINT; Q00566; -.
DR STRING; 10116.ENSRNOP00000053166; -.
DR iPTMnet; Q00566; -.
DR PhosphoSitePlus; Q00566; -.
DR PaxDb; Q00566; -.
DR PRIDE; Q00566; -.
DR ABCD; Q00566; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000106335; ENSRNOP00000094658; ENSRNOG00000056659. [Q00566-2]
DR GeneID; 29386; -.
DR KEGG; rno:29386; -.
DR CTD; 4204; -.
DR RGD; 3075; Mecp2.
DR eggNOG; KOG4161; Eukaryota.
DR GeneTree; ENSGT00530000063687; -.
DR InParanoid; Q00566; -.
DR OrthoDB; 1431783at2759; -.
DR PhylomeDB; Q00566; -.
DR TreeFam; TF332974; -.
DR Reactome; R-RNO-9022692; Regulation of MECP2 expression and activity. [Q00566-1]
DR PRO; PR:Q00566; -.
DR Proteomes; UP000002494; Chromosome X.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0000792; C:heterochromatin; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0000400; F:four-way junction DNA binding; IDA:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:RGD.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:RGD.
DR GO; GO:0003729; F:mRNA binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0035197; F:siRNA binding; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0045322; F:unmethylated CpG binding; IDA:RGD.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0032048; P:cardiolipin metabolic process; ISO:RGD.
DR GO; GO:0006576; P:cellular biogenic amine metabolic process; ISO:RGD.
DR GO; GO:0071317; P:cellular response to isoquinoline alkaloid; IDA:RGD.
DR GO; GO:0035865; P:cellular response to potassium ion; IDA:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:0016358; P:dendrite development; ISO:RGD.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0008211; P:glucocorticoid metabolic process; ISO:RGD.
DR GO; GO:0006541; P:glutamine metabolic process; ISO:RGD.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0031507; P:heterochromatin assembly; ISO:RGD.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0016573; P:histone acetylation; ISO:RGD.
DR GO; GO:0016571; P:histone methylation; ISO:RGD.
DR GO; GO:0006020; P:inositol metabolic process; ISO:RGD.
DR GO; GO:0007612; P:learning; ISO:RGD.
DR GO; GO:0007616; P:long-term memory; ISO:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0048286; P:lung alveolus development; IEP:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0007052; P:mitotic spindle organization; ISO:RGD.
DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IDA:RGD.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:1903860; P:negative regulation of dendrite extension; IMP:RGD.
DR GO; GO:0061000; P:negative regulation of dendritic spine development; IMP:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
DR GO; GO:0090327; P:negative regulation of locomotion involved in locomotory behavior; IMP:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:2000635; P:negative regulation of primary miRNA processing; IMP:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:RGD.
DR GO; GO:1903941; P:negative regulation of respiratory gaseous exchange; IMP:RGD.
DR GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:2000820; P:negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0001976; P:nervous system process involved in regulation of systemic arterial blood pressure; ISO:RGD.
DR GO; GO:0050905; P:neuromuscular process; ISO:RGD.
DR GO; GO:0050884; P:neuromuscular process controlling posture; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IEP:RGD.
DR GO; GO:0042551; P:neuron maturation; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0021772; P:olfactory bulb development; IEP:RGD.
DR GO; GO:0014003; P:oligodendrocyte development; IEP:RGD.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; ISO:RGD.
DR GO; GO:1901953; P:positive regulation of anterograde dense core granule transport; IMP:RGD.
DR GO; GO:1905492; P:positive regulation of branching morphogenesis of a nerve; IMP:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IMP:RGD.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:RGD.
DR GO; GO:1905643; P:positive regulation of DNA methylation; ISO:RGD.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:1900114; P:positive regulation of histone H3-K9 trimethylation; ISO:RGD.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISO:RGD.
DR GO; GO:1901956; P:positive regulation of retrograde dense core granule transport; IMP:RGD.
DR GO; GO:0031915; P:positive regulation of synaptic plasticity; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0021740; P:principal sensory nucleus of trigeminal nerve development; IEP:RGD.
DR GO; GO:0019230; P:proprioception; ISO:RGD.
DR GO; GO:0008104; P:protein localization; ISO:RGD.
DR GO; GO:0099611; P:regulation of action potential firing threshold; IMP:RGD.
DR GO; GO:0044030; P:regulation of DNA methylation; IMP:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006349; P:regulation of gene expression by genomic imprinting; ISO:RGD.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISO:RGD.
DR GO; GO:0051570; P:regulation of histone H3-K9 methylation; ISO:RGD.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; ISO:RGD.
DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; ISO:RGD.
DR GO; GO:0042220; P:response to cocaine; IDA:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0010212; P:response to ionizing radiation; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0051707; P:response to other organism; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
DR GO; GO:0035176; P:social behavior; IMP:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0001964; P:startle response; ISO:RGD.
DR GO; GO:0021756; P:striatum development; IEP:RGD.
DR GO; GO:0007416; P:synapse assembly; ISO:RGD.
DR GO; GO:0021794; P:thalamus development; IEP:RGD.
DR GO; GO:0021591; P:ventricular system development; ISO:RGD.
DR GO; GO:0008542; P:visual learning; ISO:RGD.
DR InterPro; IPR016177; DNA-bd_dom_sf.
DR InterPro; IPR017353; Me_CpG-bd_MeCP2.
DR InterPro; IPR045138; MeCP2/MBD4.
DR InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR PANTHER; PTHR15074; PTHR15074; 1.
DR Pfam; PF01429; MBD; 1.
DR PIRSF; PIRSF038006; Methyl_CpG_bd_MeCP2; 1.
DR SMART; SM00391; MBD; 1.
DR SUPFAM; SSF54171; SSF54171; 1.
DR PROSITE; PS50982; MBD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Direct protein sequencing; DNA-binding;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..492
FT /note="Methyl-CpG-binding protein 2"
FT /id="PRO_0000096348"
FT DOMAIN 90..162
FT /note="MBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT DNA_BIND 185..197
FT /note="A.T hook 1"
FT DNA_BIND 265..277
FT /note="A.T hook 2"
FT REGION 1..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..309
FT /note="Interaction with NCOR2"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6"
FT REGION 285..309
FT /note="Interaction with TBL1XR1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6"
FT REGION 325..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 83..109
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..267
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..398
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..492
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17046689,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51608"
FT MOD_RES 162
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51608"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17046689,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 321
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6"
FT MOD_RES 421
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:17046689"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51608"
FT MOD_RES 455
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51608"
FT VAR_SEQ 1..10
FT /note="MVAGMLGLRK -> MAAAAAAAAAAAAAAAAAAAAAAAAPSGGGGGEEERLE
FT (in isoform B)"
FT /evidence="ECO:0000303|PubMed:16670375"
FT /id="VSP_022950"
FT CONFLICT 10
FT /note="K -> E (in Ref. 2; ABI55238)"
FT /evidence="ECO:0000305"
SQ 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
