Seroatlas · Human Serome Atlas

MECP2

Methyl-CpG-binding protein 2

Also known as: MECP2_HUMAN, MRX16, MRX79, RTT

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P51608
Gene: MECP2
Ensembl: ENSG00000169057
Chromosome: X
Canonical length: 486 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Nucleoplasm

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

486 residues, UniProt reviewed canonical sequence.

>P51608|MECP2
     1  MVAGMLGLRE EKSEDQDLQG LKDKPLKFKK VKKDKKEEKE GKHEPVQPSA HHSAEPAEAG
    61  KAETSEGSGS APAVPEASAS PKQRRSIIRD RGPMYDDPTL PEGWTRKLKQ RKSGRSAGKY
   121  DVYLINPQGK AFRSKVELIA YFEKVGDTSL DPNDFDFTVT GRGSPSRREQ KPPKKPKSPK
   181  APGTGRGRGR PKGSGTTRPK AATSEGVQVK RVLEKSPGKL LVKMPFQTSP GGKAEGGGAT
   241  TSTQVMVIKR PGRKRKAEAD PQAIPKKRGR KPGSVVAAAA AEAKKKAVKE SSIRSVQETV
   301  LPIKKRKTRE TVSIEVKEVV KPLLVSTLGE KSGKGLKTCK SPGRKSKESS PKGRSSSASS
   361  PPKKEHHHHH HHSESPKAPV PLLPPLPPPP PEPESSEDPT SPPEPQDLSS SVCKEEKMPR
   421  GGSLESDGCP KEPAKTQPAV ATAATAAEKY KHRGEGERKD IVSSSMPRPN REEPVDSRTP
   481  VTERVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MECP2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.69
Highest tissue expression: 27 nTPM

Expression across tissuesHPA

Tissue

skeletal muscle: 27 nTPM
bone marrow: 24 nTPM
cerebellum: 22 nTPM
retina: 21 nTPM
ovary: 21 nTPM
lung: 21 nTPM

Single-cell type

neutrophils: 605 nCPM
mast cells: 251 nCPM
neutrophil progenitors: 244 nCPM
t-cells: 243 nCPM
monocytes: 240 nCPM
cone photoreceptor cells: 236 nCPM

Immune cell

basophil: 48 nTPM
neutrophil: 23 nTPM
eosinophil: 20 nTPM
gdT-cell: 9.2 nTPM
non-classical monocyte: 8.3 nTPM
memory B-cell: 7.9 nTPM

Brain region

cerebellum: 70 nTPM
cerebral cortex: 67 nTPM
white matter: 63 nTPM
medulla oblongata: 60 nTPM
midbrain: 60 nTPM
thalamus: 59 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MECP2.

Disease | AllUniProt

Conditions MECP2 is implicated in, by any mechanism.

Angelman syndrome (AS) MIM:105830
Intellectual developmental disorder, X-linked, syndromic 13 (MRXS13) MIM:300055
Rett syndrome (RTT) MIM:312750
Autism, X-linked 3 (AUTSX3) MIM:300496
Encephalopathy, neonatal severe, due to MECP2 mutations (ENS-MECP2) MIM:300673
Intellectual developmental disorder, X-linked, syndromic, Lubs type (MRXSL) MIM:300260

Disease | GeneticClinVar

829 pathogenic / likely-pathogenic of 2,105 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Rett syndrome
Severe neonatal-onset encephalopathy with microcephaly
X-linked intellectual disability-psychosis-macroorchidism syndrome
Inborn genetic diseases
Syndromic X-linked intellectual disability Lubs type

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.41
gnomAD pLI: 0.89
gnomAD missense Z: -1.21
DepMap mean gene effect: 0.06
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MECP2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MECP2 as an antibody target. Whether an autoantibody or antibody against MECP2 could matter depends on whether native MECP2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MECP2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label MECP2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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