MBD5

Protein identityUniProt · HPA

UniProt accession

Q9P267

Gene

MBD5

Ensembl

ENSG00000204406

Chromosome

2

Canonical length

1494 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Midbody

OverviewNCBI Gene

This gene encodes a member of the methyl-CpG-binding domain (MBD) family. The MBD consists of about 70 residues and is the minimal region required for a methyl-CpG-binding protein binding specifically to methylated DNA. In addition to the MBD domain, this protein contains a PWWP domain (Pro-Trp-Trp-Pro motif), which consists of 100-150 amino acids and is found in numerous proteins that are involved in cell division, growth and differentiation. Mutations in this gene cause an autosomal dominant type of cognitive disability. The encoded protein interacts with the polycomb repressive complex PR-DUB which catalyzes the deubiquitination of a lysine residue of histone 2A. Haploinsufficiency of this gene is associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures. Alternatively spliced transcript variants have been found, but their full-length nature is not determined. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

1494 residues, UniProt reviewed canonical sequence.

>Q9P267|MBD5
     1  MNGGKECDGG DKEGGLPAIQ VPVGWQRRVD QNGVLYVSPS GSLLSCLEQV KTYLLTDGTC
    61  KCGLECPLIL PKVFNFDPGA AVKQRTAEDV KADEDVTKLC IHKRKIIAVA TLHKSMEAPH
   121  PSLVLTSPGG GTNATPVVPS RAATPRSVRN KSHEGITNSV MPECKNPFKL MIGSSNAMGR
   181  LYVQELPGSQ QQELHPVYPR QRLGSSEHGQ KSPFRGSHGG LPSPASSGSQ IYGDGSISPR
   241  TDPLGSPDVF TRSNPGFHGA PNSSPIHLNR TPLSPPSVML HGSPVQSSCA MAGRTNIPLS
   301  PTLTTKSPVM KKPMCNFSTN MEIPRAMFHH KPPQGPPPPP PPSCALQKKP LTSEKDPLGI
   361  LDPIPSKPVN QNPVIINPTS FHSNVHSQVP MMNVSMPPAV VPLPSNLPLP TVKPGHMNHG
   421  SHVQRVQHSA STSLSPSPVT SPVHMMGTGI GRIEASPQRS RSSSTSSDHG NFMMPPVGPQ
   481  ATSSGIKVPP RSPRSTIGSP RPSMPSSPST KSDGHHQYKD IPNPLIAGIS NVLNTPSSAA
   541  FPTASAGSSS VKSQPGLLGM PLNQILNQHN AASFPASSLL SAAAKAQLAN QNKLAGNNSS
   601  SSSNSGAVAG SGNTEGHSTL NTMFPPTANM LLPTGEGQSG RAALRDKLMS QQKDALRKRK
   661  QPPTTVLSLL RQSQMDSSAV PKPGPDLLRK QGQGSFPISS MSQLLQSMSC QSSHLSSNST
   721  PGCGASNTAL PCSANQLHFT DPSMNSSVLQ NIPLRGEAVH CHNANTNFVH SNSPVPNHHL
   781  AGLINQIQAS GNCGMLSQSG MALGNSLHPN PPQSRISTSS TPVIPNSIVS SYNQTSSEAG
   841  GSGPSSSIAI AGTNHPAITK TTSVLQDGVI VTTAAGNPLQ SQLPIGSDFP FVGQEHALHF
   901  PSNSTSNNHL PHPLNPSLLS SLPISLPVNQ QHLLNQNLLN ILQPSAGEGD MSSINNTLSN
   961  HQLTHLQSLL NNNQMFPPNQ QQQQLLQGYQ NLQAFQGQST IPCPANNNPM ACLFQNFQVR
  1021  MQEDAALLNK RISTQPGLTA LPENPNTTLP PFQDTPCELQ PRIDPSLGQQ VKDGLVVGGP
  1081  GDASVDAIYK AVVDAASKGM QVVITTAVNS TTQISPIPAL SAMSAFTASI GDPLNLSSAV
  1141  SAVIHGRNMG GVDHDGRLRN SRGARLPKNL DHGKNVNEGD GFEYFKSASC HTSKKQWDGE
  1201  QSPRGERNRW KYEEFLDHPG HIHSSPCHER PNNVSTLPFL PGEQHPILLP PRNCPGDKIL
  1261  EENFRYNNYK RTMMSFKERL ENTVERCAHI NGNRPRQSRG FGELLSTAKQ DLVLEEQSPS
  1321  SSNSLENSLV KDYIHYNGDF NAKSVNGCVP SPSDAKSISS EDDLRNPDSP SSNELIHYRP
  1381  RTFNVGDLVW GQIKGLTSWP GKLVREDDVH NSCQQSPEEG KVEPEKLKTL TEGLEAYSRV
  1441  RKRNRKSGKL NNHLEAAIHE AMSELDKMSG TVHQIPQGDR QMRPPKPKRR KISR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MBD5 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)

0.64

Highest tissue expression

5.3 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MBD5.

Disease | AllUniProt

Conditions MBD5 is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal dominant 1 (MRD1) MIM:156200

Disease | GeneticClinVar

128 pathogenic / likely-pathogenic of 1,811 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal dominant 1
• Inborn genetic diseases
• Intellectual disability
• Schizophrenia
• Autism spectrum disorder

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)

0.14

gnomAD pLI

1

gnomAD missense Z

0.86

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glucose homeostasis
• nervous system development
• positive regulation of growth hormone receptor signaling pathway
• regulation of behavior
• regulation of multicellular organism growth

Molecular functions

• chromatin binding

Cellular components

• chromocenter
• chromosome
• extracellular exosome
• midbody
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• PWWP domain
• Methyl-CpG DNA binding
• DNA-binding domain superfamily

KeywordsUniProt

• Chromosome
• Intellectual disability
• Nucleus
• Ubl conjugation pathway