MBD4

Protein identityUniProt · HPA

UniProt accession

O95243

Gene

MBD4

Ensembl

ENSG00000129071

Chromosome

3

Canonical length

580 aa

Protein class

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

Subcellular location

Nuclear speckles

OverviewNCBI Gene

The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

Canonical amino-acid sequenceUniProt

580 residues, UniProt reviewed canonical sequence.

>O95243|MBD4
     1  MGTTGLESLS LGDRGAAPTV TSSERLVPDP PNDLRKEDVA MELERVGEDE EQMMIKRSSE
    61  CNPLLQEPIA SAQFGATAGT ECRKSVPCGW ERVVKQRLFG KTAGRFDVYF ISPQGLKFRS
   121  KSSLANYLHK NGETSLKPED FDFTVLSKRG IKSRYKDCSM AALTSHLQNQ SNNSNWNLRT
   181  RSKCKKDVFM PPSSSSELQE SRGLSNFTST HLLLKEDEGV DDVNFRKVRK PKGKVTILKG
   241  IPIKKTKKGC RKSCSGFVQS DSKRESVCNK ADAESEPVAQ KSQLDRTVCI SDAGACGETL
   301  SVTSEENSLV KKKERSLSSG SNFCSEQKTS GIINKFCSAK DSEHNEKYED TFLESEEIGT
   361  KVEVVERKEH LHTDILKRGS EMDNNCSPTR KDFTGEKIFQ EDTIPRTQIE RRKTSLYFSS
   421  KYNKEALSPP RRKAFKKWTP PRSPFNLVQE TLFHDPWKLL IATIFLNRTS GKMAIPVLWK
   481  FLEKYPSAEV ARTADWRDVS ELLKPLGLYD LRAKTIVKFS DEYLTKQWKY PIELHGIGKY
   541  GNDSYRIFCV NEWKQVHPED HKLNKYHDWL WENHEKLSLS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MBD4 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)

0.57

Highest tissue expression

69 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MBD4.

Disease | AllUniProt

Conditions MBD4 is implicated in, by any mechanism.

• Tumor predisposition syndrome 2 (TPDS2) MIM:619975
• Melanoma, uveal, 1 (UVM1) MIM:606660

Disease | GeneticClinVar

138 pathogenic / likely-pathogenic of 1,346 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Inborn genetic diseases
• Tumor predisposition syndrome 2
• MBD4-related disorder
• Melanoma, uveal, susceptibility to, 1
• Ovarian serous cystadenocarcinoma

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)

1.24

gnomAD pLI

0

gnomAD missense Z

0.46

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• depyrimidination
• DNA repair
• response to estradiol

Molecular functions

• DNA binding
• DNA endonuclease activity
• DNA N-glycosylase activity
• pyrimidine-specific mismatch base pair DNA N-glycosylase activity
• satellite DNA binding

Cellular components

• nuclear speck
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Methyl-CpG DNA binding
• DNA glycosylase
• DNA-binding domain superfamily
• Methyl-CpG binding protein MeCP2/MBD4
• Methyl-CpG binding domain
• Methyl-CpG-binding domain protein 4

KeywordsUniProt

• DNA damage
• DNA repair
• DNA-binding
• Hydrolase
• Nucleus
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of MBD4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MLH1
• FADD