MECP2

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

Methyl-CpG Binding Protein 2

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).

Adult locomotory behavior Source: Ensembl
Behavioral fear response Source: Ensembl
Cardiolipin metabolic process Source: Ensembl
Cellular biogenic amine metabolic process Source: Ensembl
Cerebellum development Source: Ensembl
Dendrite development Source: Ensembl
Excitatory postsynaptic potential Source: Ensembl
Glucocorticoid metabolic process Source: Ensembl
Glutamine metabolic process Source: Ensembl
Heterochromatin assembly Source: Ensembl
Histone acetylation Source: Ensembl
Histone methylation Source: Ensembl
Inositol metabolic process Source: Ensembl
Long-term memory Source: Ensembl
Long-term synaptic potentiation Source: Ensembl
Mitotic spindle organization Source: CAFA
Negative regulation of angiogenesis Source: BHF-UCL
Negative regulation of blood vessel endothelial cell migration Source: BHF-UCL
Negative regulation of gene expression Source: BHF-UCL
Negative regulation of neuron apoptotic process Source: Ensembl
Negative regulation of smooth muscle cell differentiation Source: Ensembl
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: GO_Central
Negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation Source: Ensembl
Nervous system process involved in regulation of systemic arterial blood pressure Source: Ensembl
Neuron maturation Source: Ensembl
Phosphatidylcholine metabolic process Source: Ensembl
Positive regulation of cell population proliferation Source: CAFA
Positive regulation of DNA methylation Source: BHF-UCL
Positive regulation of G2/M transition of mitotic cell cycle Source: CAFA
Positive regulation of histone H3-K9 trimethylation Source: Ensembl
Positive regulation of microtubule nucleation Source: CAFA
Positive regulation of transcription by RNA polymerase II Source: Ensembl
Post-embryonic development Source: Ensembl
Proprioception Source: Ensembl
Protein localization Source: Ensembl
Regulation of gene expression by genomic imprinting Source: MGI
Regulation of respiratory gaseous exchange by nervous system process Source: Ensembl
Respiratory gaseous exchange by respiratory system Source: Ensembl
Response to hypoxia Source: Ensembl
Response to other organism Source: Ensembl
Sensory perception of pain Source: Ensembl
Social behavior Source: Ensembl
Startle response Source: Ensembl
Synapse assembly Source: Ensembl
Ventricular system development Source: Ensembl
Visual learning Source: Ensembl

Nucleus
Note: Colocalized with methyl-CpG in the genome. Colocalized with TBL1X to the heterochromatin foci.

Angelman syndrome (AS):
A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue.
Intellectual developmental disorder, X-linked, syndromic 13 (MRXS13):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS13 patients manifest mental retardation associated with other variable features such as spasticity, episodes of manic depressive psychosis, increased tone and macroorchidism.
Rett syndrome (RTT):
An X-linked dominant neurodevelopmental disorder, and one of the most common causes of mental retardation in females. Patients appear to develop normally until 6 to 18 months of age, then gradually lose speech and purposeful hand movements, and develop microcephaly, seizures, autism, ataxia, mental retardation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood.
Autism, X-linked 3 (AUTSX3):
A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.
Encephalopathy, neonatal severe, due to MECP2 mutations (ENS-MECP2):
The disease is caused by variants affecting the gene represented in this entry. The MECP2 gene is mutated in Rett syndrome, a severe neurodevelopmental disorder that almost always occurs in females. Although it was first thought that MECP2 mutations causing Rett syndrome were lethal in males, later reports identified a severe neonatal encephalopathy in surviving male sibs of patients with Rett syndrome. Additional reports have confirmed a severe phenotype in males with Rett syndrome-associated MECP2 mutations.
A neurodevelopmental disorder characterized by severe neonatal encephalopathy, developmental delay, mental retardation, microcephaly, seizures. Additional features include respiratory insufficiency and central hypoventilation, gastroesophageal reflux, axial hypotonia, hyperreflexia and dyskinetic movements.
Intellectual developmental disorder, X-linked, syndromic, Lubs type (MRXSL):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSL patients manifest mental retardation associated with variable features. They include swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections, hypotonia, mild myopathy and characteristic facies such as downslanting palpebral fissures, hypertelorism and a short nose with a low nasal bridge.

Phosphorylated on Ser-423 in brain upon synaptic activity, which attenuates its repressor activity and seems to regulate dendritic growth and spine maturation.