Methyl-CpG-binding domain protein 4

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O95243 (MBD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 91. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Methyl-CpG-binding domain protein 4
EC=3.2.2.-

Alternative name(s):
Methyl-CpG-binding endonuclease 1
Methyl-CpG-binding protein MBD4
Mismatch-specific DNA N-glycosylase

Gene names

Name:	MBD4
Synonyms:	MED1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	580 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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.9
Subunit structure	Interacts with MLH1. Ref.3 Ref.10
Subcellular location	Nucleus.
Sequence similarities	Contains 1 MBD (methyl-CpG-binding) domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	depyrimidination Traceable author statement. Source: Reactome
Cellular component	nucleoplasm Traceable author statement. Source: Reactome
Molecular function	endodeoxyribonuclease activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction Ref.10. Source: IntAct satellite DNA binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FADD	Q13158	6	EBI-348011,EBI-494804

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.

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 580

580

Methyl-CpG-binding domain protein 4

PRO_0000096264

Regions

Domain

76 – 148

MBD

Sites

Active site

560

By similarity

Natural variations

Alternative sequence

395 – 400

Missing in isoform 2.

VSP_010816

Alternative sequence

539 – 540

KY → AP in isoform 3.

VSP_010817

Alternative sequence

541 – 580

Missing in isoform 3.

VSP_010818

Natural variant

C → R.
Corresponds to variant rs2307296 [ dbSNP | Ensembl ].

VAR_029306

Natural variant

273

A → S. Ref.6
Corresponds to variant rs10342 [ dbSNP | Ensembl ].

VAR_019357

Natural variant

273

A → T.
Corresponds to variant rs10342 [ dbSNP | Ensembl ].

VAR_019514

Natural variant

342

S → P. Ref.6
Corresponds to variant rs2307289 [ dbSNP | Ensembl ].

VAR_019358

Natural variant

346

E → K. Ref.6
Corresponds to variant rs140693 [ dbSNP | Ensembl ].

VAR_019359

Natural variant

358

I → T.
Corresponds to variant rs2307298 [ dbSNP | Ensembl ].

VAR_019515

Natural variant

568

D → H. Ref.6
Corresponds to variant rs2307293 [ dbSNP | Ensembl ].

VAR_019360

Secondary structure

580

Helix Strand Turn

Details...

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: BF16FB21A34B8E5F Show »	FASTA	580	66,051
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 [UniParc]. Checksum: 33809A26A2E61A26 Show »	FASTA	574	65,348
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 KDFTEDTIPR TQIERRKTSL YFSSKYNKEA 430 440 450 460 470 480 LSPPRRKAFK KWTPPRSPFN LVQETLFHDP WKLLIATIFL NRTSGKMAIP VLWKFLEKYP 490 500 510 520 530 540 SAEVARTADW RDVSELLKPL GLYDLRAKTI VKFSDEYLTK QWKYPIELHG IGKYGNDSYR 550 560 570 IFCVNEWKQV HPEDHKLNKY HDWLWENHEK LSLS « Hide
Isoform 3 [UniParc]. Checksum: 3131CE4F9A488371 Show »	FASTA	540	60,949
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 PIELHGIGAP « Hide

References

	« Hide 'large scale' referencesShow '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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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.
[9]	"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.
[10]	"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.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CH471052 Genomic DNA. Translation: EAW79251.1.
CH471052 Genomic DNA. Translation: EAW79253.1.
CH471052 Genomic DNA. Translation: EAW79254.1.
CH471052 Genomic DNA. Translation: EAW79255.1.
BC011752 mRNA. Translation: AAH11752.1.

IPI

IPI00426727.
IPI00426728.
IPI00426729.

RefSeq

NP_003916.1. NM_003925.1.

UniGene

Hs.35947.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IHO	X-ray	2.70	A	437-574	[»]

ProteinModelPortal

O95243.

SMR

O95243. Positions 79-154, 437-574.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95243. 3 interactions.

MINT

MINT-264766.

STRING

O95243.

PTM databases

PhosphoSite

O95243.

Proteomic databases

PRIDE

O95243.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000249910; ENSP00000249910; ENSG00000129071.

GeneID

8930.

KEGG

hsa:8930.

UCSC

uc003emh.1. human.
uc003emi.1. human.
uc003emj.1. human.

Organism-specific databases

CTD

8930.

GeneCards

GC03M129149.

H-InvDB

HIX0003669.

HGNC

HGNC:6919. MBD4.

HPA

HPA002031.

MIM

603574. gene.

neXtProt

NX_O95243.

PharmGKB

PA30663.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07000.

GeneTree

ENSGT00530000063687.

HOGENOM

HBG716172.

HOVERGEN

HBG052418.

InParanoid

O95243.

OMA

DFTVLSK.

PhylomeDB

O95243.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

O95243.

Bgee

O95243.

CleanEx

HS_MBD4.
HS_MED1.

Genevestigator

O95243.

GermOnline

ENSG00000129071. Homo sapiens.

Family and domain databases

InterPro

IPR016177. DNA-bd_integrase-typ.
IPR011257. DNA_glycosylase.
IPR003265. HhH-GPD_domain.
IPR017352. Me_CpG-bd_MBD4.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]

Gene3D

G3DSA:1.10.340.30. DNA_glycosylase. 1 hit.
G3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.

K10801.

Pfam

PF00730. HhH-GPD. 1 hit.
PF01429. MBD. 1 hit.
[Graphical view]

PIRSF

PIRSF038005. Methyl_CpG_bd_MBD4. 1 hit.

SMART

SM00391. MBD. 1 hit.
[Graphical view]

SUPFAM

SSF54171. DNA-binding_integrase-type. 1 hit.
SSF48150. DNA_glycsylse. 1 hit.

PROSITE

PS50982. MBD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

33578.

SOURCE

Search...

Entry information

Entry name

MBD4_HUMAN

Accession

Primary (citable) accession number: O95243
Secondary accession number(s): D3DNC3

Q96F09

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents