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Protein

Methyl-CpG-binding domain protein 4

Gene

MBD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei560By similarity1

GO - Molecular functioni

  • DNA N-glycosylase activity Source: Reactome
  • endodeoxyribonuclease activity Source: ProtInc
  • pyrimidine-specific mismatch base pair DNA N-glycosylase activity Source: MGI
  • satellite DNA binding Source: ProtInc

GO - Biological processi

  • depyrimidination Source: Reactome
  • DNA repair Source: ProtInc
  • response to estradiol Source: Ensembl
  • response to radiation Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129071-MONOMER.
ReactomeiR-HSA-110328. Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
R-HSA-110329. Cleavage of the damaged pyrimidine.
R-HSA-110357. Displacement of DNA glycosylase by APEX1.

Names & Taxonomyi

Protein namesi
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 namesi
Name:MBD4
Synonyms:MED1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6919. MBD4.

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi8930.
OpenTargetsiENSG00000129071.
PharmGKBiPA30663.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000962641 – 580Methyl-CpG-binding domain protein 4Add BLAST580

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei318PhosphoserineCombined sources1
Modified residuei428PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95243.
MaxQBiO95243.
PaxDbiO95243.
PeptideAtlasiO95243.
PRIDEiO95243.
TopDownProteomicsiO95243-3. [O95243-3]

PTM databases

iPTMnetiO95243.
PhosphoSitePlusiO95243.

Expressioni

Gene expression databases

BgeeiENSG00000129071.
CleanExiHS_MBD4.
HS_MED1.
ExpressionAtlasiO95243. baseline and differential.
GenevisibleiO95243. HS.

Organism-specific databases

HPAiHPA002031.

Interactioni

Subunit structurei

Interacts with MLH1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FADDQ131586EBI-348011,EBI-494804

Protein-protein interaction databases

BioGridi114444. 25 interactors.
IntActiO95243. 15 interactors.
MINTiMINT-264766.
STRINGi9606.ENSP00000249910.

Structurei

Secondary structure

1580
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi91 – 96Combined sources6
Turni101 – 104Combined sources4
Beta strandi106 – 111Combined sources6
Helixi121 – 130Combined sources10
Helixi138 – 140Combined sources3
Helixi449 – 452Combined sources4
Helixi456 – 465Combined sources10
Turni466 – 468Combined sources3
Helixi471 – 484Combined sources14
Helixi488 – 491Combined sources4
Helixi496 – 503Combined sources8
Helixi504 – 506Combined sources3
Helixi509 – 525Combined sources17
Helixi531 – 533Combined sources3
Helixi539 – 548Combined sources10
Helixi553 – 555Combined sources3
Helixi561 – 577Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MOENMR-A80-148[»]
3IHOX-ray2.70A437-574[»]
4DK9X-ray2.76A426-580[»]
4E9EX-ray1.90A427-580[»]
4E9FX-ray1.79A427-580[»]
4E9GX-ray2.35A427-580[»]
4E9HX-ray3.00A427-580[»]
4EA4X-ray2.00A427-574[»]
4EA5X-ray2.14A427-580[»]
4LG7X-ray2.50A83-149[»]
4OFAX-ray1.55A426-580[»]
4OFEX-ray2.15A426-580[»]
4OFHX-ray2.22A426-580[»]
5CHZX-ray1.83A426-580[»]
ProteinModelPortaliO95243.
SMRiO95243.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95243.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 148MBDPROSITE-ProRule annotationAdd BLAST73

Sequence similaritiesi

Contains 1 MBD (methyl-CpG-binding) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4161. Eukaryota.
ENOG4111HPQ. LUCA.
GeneTreeiENSGT00530000063687.
HOGENOMiHOG000113489.
HOVERGENiHBG052418.
InParanoidiO95243.
KOiK10801.
OMAiTADWRDV.
OrthoDBiEOG091G05HO.
PhylomeDBiO95243.
TreeFamiTF329176.

Family and domain databases

Gene3Di1.10.340.30. 1 hit.
3.30.890.10. 1 hit.
InterProiIPR016177. DNA-bd_dom.
IPR011257. DNA_glycosylase.
IPR017352. MBD4.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamiPF01429. MBD. 1 hit.
[Graphical view]
PIRSFiPIRSF038005. Methyl_CpG_bd_MBD4. 1 hit.
SMARTiSM00391. MBD. 1 hit.
[Graphical view]
SUPFAMiSSF48150. SSF48150. 1 hit.
SSF54171. SSF54171. 1 hit.
PROSITEiPS50982. MBD. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95243-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGTTGLESLS LGDRGAAPTV TSSERLVPDP PNDLRKEDVA MELERVGEDE
60 70 80 90 100
EQMMIKRSSE CNPLLQEPIA SAQFGATAGT ECRKSVPCGW ERVVKQRLFG
110 120 130 140 150
KTAGRFDVYF ISPQGLKFRS KSSLANYLHK NGETSLKPED FDFTVLSKRG
160 170 180 190 200
IKSRYKDCSM AALTSHLQNQ SNNSNWNLRT RSKCKKDVFM PPSSSSELQE
210 220 230 240 250
SRGLSNFTST HLLLKEDEGV DDVNFRKVRK PKGKVTILKG IPIKKTKKGC
260 270 280 290 300
RKSCSGFVQS DSKRESVCNK ADAESEPVAQ KSQLDRTVCI SDAGACGETL
310 320 330 340 350
SVTSEENSLV KKKERSLSSG SNFCSEQKTS GIINKFCSAK DSEHNEKYED
360 370 380 390 400
TFLESEEIGT KVEVVERKEH LHTDILKRGS EMDNNCSPTR KDFTGEKIFQ
410 420 430 440 450
EDTIPRTQIE RRKTSLYFSS KYNKEALSPP RRKAFKKWTP PRSPFNLVQE
460 470 480 490 500
TLFHDPWKLL IATIFLNRTS GKMAIPVLWK FLEKYPSAEV ARTADWRDVS
510 520 530 540 550
ELLKPLGLYD LRAKTIVKFS DEYLTKQWKY PIELHGIGKY GNDSYRIFCV
560 570 580
NEWKQVHPED HKLNKYHDWL WENHEKLSLS
Length:580
Mass (Da):66,051
Last modified:May 1, 1999 - v1
Checksum:iBF16FB21A34B8E5F
GO
Isoform 2 (identifier: O95243-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     395-400: Missing.

Show »
Length:574
Mass (Da):65,348
Checksum:i33809A26A2E61A26
GO
Isoform 3 (identifier: O95243-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     539-540: KY → AP
     541-580: Missing.

Note: No experimental confirmation available.
Show »
Length:540
Mass (Da):60,949
Checksum:i3131CE4F9A488371
GO
Isoform 5 (identifier: O95243-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     557-580: HPEDHKLNKYHDWLWENHEKLSLS → RLTPIHNSAHLVSEAK

Note: No experimental confirmation available.
Show »
Length:572
Mass (Da):64,768
Checksum:i8550E8B5D9372097
GO
Isoform 4 (identifier: O95243-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-401: RKSVPCGWER...DFTGEKIFQE → Q

Note: Possesses uracil DNA glycosylase but not thymine DNA glycosylase activity.
Show »
Length:262
Mass (Da):30,316
Checksum:i578F5642D59D353D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51E → G in BAG64144 (PubMed:14702039).Curated1
Sequence conflicti359G → R in BAG64144 (PubMed:14702039).Curated1
Sequence conflicti387S → L in BAG64144 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02930661C → R.Corresponds to variant rs2307296dbSNPEnsembl.1
Natural variantiVAR_019357273A → S.1 PublicationCorresponds to variant rs10342dbSNPEnsembl.1
Natural variantiVAR_019514273A → T.Corresponds to variant rs10342dbSNPEnsembl.1
Natural variantiVAR_019358342S → P.1 PublicationCorresponds to variant rs2307289dbSNPEnsembl.1
Natural variantiVAR_019359346E → K.1 PublicationCorresponds to variant rs140693dbSNPEnsembl.1
Natural variantiVAR_019515358I → T.Corresponds to variant rs2307298dbSNPEnsembl.1
Natural variantiVAR_019360568D → H.1 PublicationCorresponds to variant rs2307293dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05484583 – 401RKSVP…KIFQE → Q in isoform 4. 1 PublicationAdd BLAST319
Alternative sequenceiVSP_010816395 – 400Missing in isoform 2. 2 Publications6
Alternative sequenceiVSP_010817539 – 540KY → AP in isoform 3. 1 Publication2
Alternative sequenceiVSP_010818541 – 580Missing in isoform 3. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_054846557 – 580HPEDH…KLSLS → RLTPIHNSAHLVSEAK in isoform 5. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072250 mRNA. Translation: AAC68879.1.
AF120999, AF120997, AF120998 Genomic DNA. Translation: AAD50374.1.
AF114784 mRNA. Translation: AAD22195.1.
AM180876 mRNA. Translation: CAJ55826.1.
AF532602 mRNA. Translation: AAP97338.1.
AK303013 mRNA. Translation: BAG64144.1.
CR450305 mRNA. Translation: CAG29301.1.
AF494057 Genomic DNA. Translation: AAM00008.1.
AL449212 Genomic DNA. No translation available.
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.
CCDSiCCDS3058.1. [O95243-1]
CCDS63766.1. [O95243-5]
CCDS63767.1. [O95243-3]
CCDS63768.1. [O95243-2]
CCDS63769.1. [O95243-6]
RefSeqiNP_001263199.1. NM_001276270.1. [O95243-2]
NP_001263200.1. NM_001276271.1. [O95243-5]
NP_001263201.1. NM_001276272.1. [O95243-3]
NP_001263202.1. NM_001276273.1. [O95243-6]
NP_003916.1. NM_003925.2. [O95243-1]
UniGeneiHs.35947.

Genome annotation databases

EnsembliENST00000249910; ENSP00000249910; ENSG00000129071. [O95243-1]
ENST00000393278; ENSP00000376959; ENSG00000129071. [O95243-6]
ENST00000429544; ENSP00000394080; ENSG00000129071. [O95243-2]
ENST00000503197; ENSP00000424873; ENSG00000129071. [O95243-3]
ENST00000507208; ENSP00000422327; ENSG00000129071. [O95243-5]
GeneIDi8930.
KEGGihsa:8930.
UCSCiuc003emh.3. human. [O95243-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072250 mRNA. Translation: AAC68879.1.
AF120999, AF120997, AF120998 Genomic DNA. Translation: AAD50374.1.
AF114784 mRNA. Translation: AAD22195.1.
AM180876 mRNA. Translation: CAJ55826.1.
AF532602 mRNA. Translation: AAP97338.1.
AK303013 mRNA. Translation: BAG64144.1.
CR450305 mRNA. Translation: CAG29301.1.
AF494057 Genomic DNA. Translation: AAM00008.1.
AL449212 Genomic DNA. No translation available.
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.
CCDSiCCDS3058.1. [O95243-1]
CCDS63766.1. [O95243-5]
CCDS63767.1. [O95243-3]
CCDS63768.1. [O95243-2]
CCDS63769.1. [O95243-6]
RefSeqiNP_001263199.1. NM_001276270.1. [O95243-2]
NP_001263200.1. NM_001276271.1. [O95243-5]
NP_001263201.1. NM_001276272.1. [O95243-3]
NP_001263202.1. NM_001276273.1. [O95243-6]
NP_003916.1. NM_003925.2. [O95243-1]
UniGeneiHs.35947.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MOENMR-A80-148[»]
3IHOX-ray2.70A437-574[»]
4DK9X-ray2.76A426-580[»]
4E9EX-ray1.90A427-580[»]
4E9FX-ray1.79A427-580[»]
4E9GX-ray2.35A427-580[»]
4E9HX-ray3.00A427-580[»]
4EA4X-ray2.00A427-574[»]
4EA5X-ray2.14A427-580[»]
4LG7X-ray2.50A83-149[»]
4OFAX-ray1.55A426-580[»]
4OFEX-ray2.15A426-580[»]
4OFHX-ray2.22A426-580[»]
5CHZX-ray1.83A426-580[»]
ProteinModelPortaliO95243.
SMRiO95243.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114444. 25 interactors.
IntActiO95243. 15 interactors.
MINTiMINT-264766.
STRINGi9606.ENSP00000249910.

PTM databases

iPTMnetiO95243.
PhosphoSitePlusiO95243.

Proteomic databases

EPDiO95243.
MaxQBiO95243.
PaxDbiO95243.
PeptideAtlasiO95243.
PRIDEiO95243.
TopDownProteomicsiO95243-3. [O95243-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000249910; ENSP00000249910; ENSG00000129071. [O95243-1]
ENST00000393278; ENSP00000376959; ENSG00000129071. [O95243-6]
ENST00000429544; ENSP00000394080; ENSG00000129071. [O95243-2]
ENST00000503197; ENSP00000424873; ENSG00000129071. [O95243-3]
ENST00000507208; ENSP00000422327; ENSG00000129071. [O95243-5]
GeneIDi8930.
KEGGihsa:8930.
UCSCiuc003emh.3. human. [O95243-1]

Organism-specific databases

CTDi8930.
DisGeNETi8930.
GeneCardsiMBD4.
HGNCiHGNC:6919. MBD4.
HPAiHPA002031.
MIMi603574. gene.
neXtProtiNX_O95243.
OpenTargetsiENSG00000129071.
PharmGKBiPA30663.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4161. Eukaryota.
ENOG4111HPQ. LUCA.
GeneTreeiENSGT00530000063687.
HOGENOMiHOG000113489.
HOVERGENiHBG052418.
InParanoidiO95243.
KOiK10801.
OMAiTADWRDV.
OrthoDBiEOG091G05HO.
PhylomeDBiO95243.
TreeFamiTF329176.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129071-MONOMER.
ReactomeiR-HSA-110328. Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
R-HSA-110329. Cleavage of the damaged pyrimidine.
R-HSA-110357. Displacement of DNA glycosylase by APEX1.

Miscellaneous databases

EvolutionaryTraceiO95243.
GeneWikiiMBD4.
GenomeRNAii8930.
PROiO95243.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129071.
CleanExiHS_MBD4.
HS_MED1.
ExpressionAtlasiO95243. baseline and differential.
GenevisibleiO95243. HS.

Family and domain databases

Gene3Di1.10.340.30. 1 hit.
3.30.890.10. 1 hit.
InterProiIPR016177. DNA-bd_dom.
IPR011257. DNA_glycosylase.
IPR017352. MBD4.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamiPF01429. MBD. 1 hit.
[Graphical view]
PIRSFiPIRSF038005. Methyl_CpG_bd_MBD4. 1 hit.
SMARTiSM00391. MBD. 1 hit.
[Graphical view]
SUPFAMiSSF48150. SSF48150. 1 hit.
SSF54171. SSF54171. 1 hit.
PROSITEiPS50982. MBD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMBD4_HUMAN
AccessioniPrimary (citable) accession number: O95243
Secondary accession number(s): B4DZN2
, D3DNC3, D3DNC4, E9PEE4, Q2MD36, Q7Z4T3, Q96F09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.