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Reviewed, UniProtKB/Swiss-Prot O95243 (MBD4_HUMAN)

Last modified July 7, 2009. Version 70. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Methyl-CpG-binding domain protein 4
    EC=3.2.2.-
Alternative name(s):
    Methyl-CpG-binding protein MBD4
    Methyl-CpG-binding endonuclease 1
    Mismatch-specific DNA N-glycosylase
Gene names
Name: MBD4
Synonyms: MED1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length580 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Mismatch-specific DNA N-glycosylase involved in DNA repair. Has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites. Can also remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first identified as methyl-CpG-binding protein. Ref.3 Ref.8

Subunit structure

Interacts with MLH1. Ref.3 Ref.9

Subcellular location

Nucleus.

Sequence similarities

Contains 1 MBD (methyl-CpG-binding) domain.

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Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
   Molecular functionHydrolase
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processdepyrimidination

Inferred from Experiment. Source: Reactome

   Cellular componentnucleus Ref.1

Inferred from direct assay. Source: HPA

   Molecular functionendodeoxyribonuclease activity Ref.3

Traceable author statement. Source: ProtInc

protein binding Ref.9

Inferred from physical interaction. Source: IntAct

satellite DNA binding Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

CSNK2BP678701EBI-348011,EBI-348169
FADDQ131585EBI-348011,EBI-494804

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95243-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O95243-2)

The sequence of this isoform differs from the canonical sequence as follows:
     395-400: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: O95243-3)

The sequence of this isoform differs from the canonical sequence as follows:
     539-540: KY → AP
     541-580: Missing.
Note: No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 580580Methyl-CpG-binding domain protein 4
PRO_0000096264

Regions

Domain76 – 14873MBD

Sites

Active site5601 By similarity

Natural variations

Alternative sequence395 – 4006Missing in isoform 2.
VSP_010816
Alternative sequence539 – 5402KY → AP in isoform 3.
VSP_010817
Alternative sequence541 – 58040Missing in isoform 3.
VSP_010818
Natural variant611C → R: dbSNP rs2307296.
VAR_029306
Natural variant2731A → S: dbSNP rs10342. Ref.6
VAR_019357
Natural variant2731A → T: dbSNP rs10342. Ref.6
VAR_019514
Natural variant3421S → P: dbSNP rs2307289. Ref.6
VAR_019358
Natural variant3461E → K: dbSNP rs140693. Ref.6
VAR_019359
Natural variant3581I → T: dbSNP rs2307298.
VAR_019515
Natural variant5681D → H: dbSNP rs2307293. Ref.6
VAR_019360

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: BF16FB21A34B8E5F

FASTA58066,051
        10         20         30         40         50         60 
MGTTGLESLS LGDRGAAPTV TSSERLVPDP PNDLRKEDVA MELERVGEDE EQMMIKRSSE 

        70         80         90        100        110        120 
CNPLLQEPIA SAQFGATAGT ECRKSVPCGW ERVVKQRLFG KTAGRFDVYF ISPQGLKFRS 

       130        140        150        160        170        180 
KSSLANYLHK NGETSLKPED FDFTVLSKRG IKSRYKDCSM AALTSHLQNQ SNNSNWNLRT 

       190        200        210        220        230        240 
RSKCKKDVFM PPSSSSELQE SRGLSNFTST HLLLKEDEGV DDVNFRKVRK PKGKVTILKG 

       250        260        270        280        290        300 
IPIKKTKKGC RKSCSGFVQS DSKRESVCNK ADAESEPVAQ KSQLDRTVCI SDAGACGETL 

       310        320        330        340        350        360 
SVTSEENSLV KKKERSLSSG SNFCSEQKTS GIINKFCSAK DSEHNEKYED TFLESEEIGT 

       370        380        390        400        410        420 
KVEVVERKEH LHTDILKRGS EMDNNCSPTR KDFTGEKIFQ EDTIPRTQIE RRKTSLYFSS 

       430        440        450        460        470        480 
KYNKEALSPP RRKAFKKWTP PRSPFNLVQE TLFHDPWKLL IATIFLNRTS GKMAIPVLWK 

       490        500        510        520        530        540 
FLEKYPSAEV ARTADWRDVS ELLKPLGLYD LRAKTIVKFS DEYLTKQWKY PIELHGIGKY 

       550        560        570        580 
GNDSYRIFCV NEWKQVHPED HKLNKYHDWL WENHEKLSLS

« Hide

Isoform 2.

Checksum: 33809A26A2E61A26
Show »

FASTA57465,348
Isoform 3.

Checksum: 3131CE4F9A488371
Show »

FASTA54060,949

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References

« Hide 'large scale' references
[1]"Identification and characterization of a family of mammalian methyl-CpG binding proteins."
Hendrich B., Bird A.
Mol. Cell. Biol. 18:6538-6547(1998) [PubMed: 9774669] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Genomic structure and chromosomal mapping of the murine and human mbd1, mbd2, mbd3, and mbd4 genes."
Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A.
Mamm. Genome 10:906-912(1999) [PubMed: 10441743] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1."
Bellacosa A., Cicchillitti L., Schepis F., Riccio A., Yeung A.T., Matsumoto Y., Golemis E.A., Genuardi M., Neri G.
Proc. Natl. Acad. Sci. U.S.A. 96:3969-3974(1999) [PubMed: 10097147] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH MLH1.
Tissue: Fetal brain.
[4]Guo J.H., Chen L., Yu L.
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Lung.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]NIEHS SNPs program
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-273; PRO-342; LYS-346 AND HIS-568.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung.
[8]"Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase."
Petronzelli F., Riccio A., Markham G.D., Seeholzer S.H., Stoerker J., Genuardi M., Yeung A.T., Matsumoto Y., Bellacosa A.
J. Biol. Chem. 275:32422-32429(2000) [PubMed: 10930409] [Abstract]
Cited for: FUNCTION.
[9]"Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: a potential link between genome surveillance and apoptosis."
Screaton R.A., Kiessling S., Sansom O.J., Millar C.B., Maddison K., Bird A., Clarke A.R., Frisch S.M.
Proc. Natl. Acad. Sci. U.S.A. 100:5211-5216(2003) [PubMed: 12702765] [Abstract]
Cited for: INTERACTION WITH FADD.
+Additional computationally mapped references.

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Web resources

NIEHS-SNPs

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Cross-references

Sequence databases

AF072250 mRNA. Translation: AAC68879.1.
AF120999, AF120997, AF120998 Genomic DNA. Translation: AAD50374.1.
AF114784 mRNA. Translation: AAD22195.1.
AF532602 mRNA. Translation: AAP97338.1.
CR450305 mRNA. Translation: CAG29301.1.
AF494057 Genomic DNA. Translation: AAM00008.1.
BC011752 mRNA. Translation: AAH11752.1.
IPIIPI00426727.
IPI00426728.
IPI00426729.
RefSeqNP_003916.1.
UniGeneHs.35947

3D structure databases

HSSPHSSP built from PDB template 1NGN based on UniProtKB Q9Z2D7.
SMRO95243. Positions 437-580.
ModBaseSearch...

Protein-protein interaction databases

IntActO95243. 2 interactions.

PTM databases

PhosphoSiteO95243.

Proteomic databases

PRIDEO95243.

Genome annotation databases

EnsemblENSG00000129071. Homo sapiens. [Contig view]
GeneID8930.
KEGGhsa:8930.
UCSCuc003emh.1. human.
uc003emi.1. human.
uc003emj.1. human.

Organism-specific databases

GeneCardsGC03M130632.
H-InvDBHIX0003669.
HGNCHGNC:6919. MBD4.
HPAHPA002031.
MIM603574. gene.
PharmGKBPA30663.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO95243.
HOVERGENO95243.
OMAO95243. YLHKNGE.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressO95243.
BgeeO95243.
CleanExHS_MBD4.
HS_MED1.
GermOnlineENSG00000129071. Homo sapiens.

Family and domain databases

InterProIPR003265. HhH-GPD_domain.
IPR017352. Methyl_CpG-bd_MBD4.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
Gene3DG3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.
PfamPF00730. HhH-GPD. 1 hit.
PF01429. MBD. 1 hit.
[Graphical view]
PIRSFPIRSF038005. Methyl_CpG_bd_MBD4. 1 hit.
SMARTSM00391. MBD. 1 hit.
[Graphical view]
PROSITEPS50982. MBD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio33578.
SOURCESearch...

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Entry information

Entry nameMBD4_HUMAN
AccessionPrimary (citable) accession number: O95243
Secondary accession number(s): Q7Z4T3, Q96F09
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1999
Last modified: July 7, 2009
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents