MeCP2

MeCP2 is a DNA-binding protein that binds to methylated DNA portions and is asscociated with silencing gene expression. This protein mainly binds DNA at methylated CpG dinucleotides such as CpG islands in the promoter region of expressed genes. Once bound it will condense the chromatin structure, form a complex with histone deacetylases (HDAC), or it will block transcription factors directly. Further studies have shown that MeCP2 may be able to bind directly to un-methylated DNA in some instances.

Names of Protein

 * AUTSX3
 * DKFZp686A24160
 * MECP 2
 * MeCP 2 protein
 * Methyl CpG binding protein 2
 * Methyl CpG binding protein 2 (Rett syndrome)
 * MRX16
 * MRX79
 * PPMX
 * RTS
 * RTT

Encoding Gene
The MECP2 gene is 76,188 bases long and is located on the long arm(q)of the X chromosome. It is at band 28 from base pair 152,808,110 to base pair 152,878,611.

Official Symbol= MECP2

Gene Id= 4204

Organism= Homo Sapien

mRNA NCBI accession number= NM_004992

protein NCBI accession number= NP_004983

Protein Structure
MeCP2 is part of a family of methyl-CpG-binding domain proteins(MBD), but posses its own unique differences which help set it apart from the group. It has two functional domains:
 * an 85 Amino acid methyl-cytosine-binding domain(MBD)
 * and a 104 Amino acid transcriptional repression domain(TRD)

The MBD domain forms a wedge and attaches to the methylated CpG sites on the DNA strands. The TRD region then reacts with SIN3A to recruit histone deacetylases (HDAC). There are also unusual, repetative sequences found at the carboxyl terminus. This region is closely related to the fork head family, at the amino acid level.

BLAST
Search Information Options: Database: cdd.v2.10 Low complexity filter: yes E-value threshold: 0.010 Max. hits: 500 Data Source: Live blast search RID = 1170725398-21766-49536286480.BLASTQ3 System: Search creator: newblast Software: blastp 2.2.15 Oct-15-2006 Service: rpsblast

Descriptions [Click to show all details] Title PssmId Multi-Dom E-value [Click to hide detail] cd01396, MeCP2_MBD, MeCP2, MBD1, MBD2, MBD3, and MBD4 are members of a protein family ... 29025 No 2e-17

cd01396, MeCP2_MBD, MeCP2, MBD1, MBD2, MBD3, and MBD4 are members of a protein family that share the methyl-CpG-binding domain (MBD). The MBD, consists of about 70 residues and is defined as the minimal region required for binding to methylated DNA by a methyl-CpG-binding protein which binds specifically to methylated DNA. The MBD can recognize a single symmetrically methylated CpG either as naked DNA or within chromatin. MeCP2, MBD1 and MBD2 (and likely MBD3) form complexes with histone deacetylase and are involved in histone deacetylase-dependent repression of transcription. MBD4 is an endonuclease that forms a complex with the DNA mismatch-repair protein MLH1.. CD Length: 77, Pct. Aligned: 100, Bit Score: 84.618358, E-value: 2e-17

10 20 30 40 50 60 70 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*... query 94 MYDDPTLPEGWTRKLKQRKSGrSAGKYDVYLINPQGKAFRSKVELIAYFEKVGDTSLDPNDFDFTV---TGRGSPSRR 168 consensus 1 KPEDPRLPPGWKRELVPRKSG-SAGKFDVYYISPTGKKFRSKVELARYLEKNGPTSLDLSDFDFTVpkkLGLGSPRRH 77

Functional Significance
MeCP2 protein is found in all cells in the body acting as transcriptional repressor, including the brain. Here it is found in high concentrations in the nuerons and is associated with maturation of the CNS system and in forming synaptic contacts.

Role in Disease
The most significant disease associated with a defect in the MeCP2 protein or its expression is a brain diorder called Rett Syndrome. In this disease the gene is mutated, so active MeCP2 protein is never made. This disease is mainly found in girls with a prevailance of around 1 in every 10,000. Patients are born normal, but after about 6 months to a year and half, speech and motor function capabilites start to decrease. This is followed by seizures, growth retardation, autistic behavior and cognitive and motor impairment. This is a X-linked dominant disease that is found predominatley affecting the paternal X chromosome. It has been linked to male lethality, due to its prevailance in females, but in rare cases some males can also be affected by Rett Syndrome.