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Protein

Methyl-CpG-binding domain protein 4

Gene

MBD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDNA-binding, Hydrolase
Biological processDNA damage, DNA repair

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000129071.9
HGNCiHGNC:6919 MBD4
MIMi603574 gene
neXtProtiNX_O95243

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi50740
50741 [O95243-2]
50742 [O95243-3]
TopDownProteomicsiO95243-3 [O95243-3]

PTM databases

iPTMnetiO95243
PhosphoSitePlusiO95243

Expressioni

Gene expression databases

BgeeiENSG00000129071 Expressed in 248 organ(s), highest expression level in secondary oocyte
CleanExiHS_MBD4
HS_MED1
ExpressionAtlasiO95243 baseline and differential
GenevisibleiO95243 HS

Organism-specific databases

HPAiHPA002031

Interactioni

Subunit structurei

Interacts with MLH1.2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi114444, 25 interactors
IntActiO95243, 16 interactors
MINTiO95243
STRINGi9606.ENSP00000249910

Structurei

Secondary structure

1580
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95243
SMRiO95243
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95243

Family & Domainsi

Domains and Repeats

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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR016177 DNA-bd_dom_sf
IPR011257 DNA_glycosylase
IPR017352 MBD4
IPR001739 Methyl_CpG_DNA-bd
PANTHERiPTHR15074:SF6 PTHR15074:SF6, 1 hit
PfamiView protein in Pfam
PF01429 MBD, 1 hit
PIRSFiPIRSF038005 Methyl_CpG_bd_MBD4, 1 hit
SMARTiView protein in SMART
SM00391 MBD, 1 hit
SUPFAMiSSF48150 SSF48150, 1 hit
SSF54171 SSF54171, 1 hit
PROSITEiView protein in PROSITE
PS50982 MBD, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

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

This entry has 5 described isoforms and 1 potential isoform that is computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RBI7D6RBI7_HUMAN
Methyl-CpG-binding domain protein 4
MBD4
52Annotation score:

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 dbSNP:rs2307296Ensembl.1
Natural variantiVAR_019357273A → S1 PublicationCorresponds to variant dbSNP:rs10342Ensembl.1
Natural variantiVAR_019514273A → T. Corresponds to variant dbSNP:rs10342Ensembl.1
Natural variantiVAR_019358342S → P1 PublicationCorresponds to variant dbSNP:rs2307289Ensembl.1
Natural variantiVAR_019359346E → K1 PublicationCorresponds to variant dbSNP:rs140693Ensembl.1
Natural variantiVAR_019515358I → T. Corresponds to variant dbSNP:rs2307298Ensembl.1
Natural variantiVAR_019360568D → H1 PublicationCorresponds to variant dbSNP:rs2307293EnsemblClinVar.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, 16 interactors
MINTiO95243
STRINGi9606.ENSP00000249910

PTM databases

iPTMnetiO95243
PhosphoSitePlusiO95243

Proteomic databases

EPDiO95243
MaxQBiO95243
PaxDbiO95243
PeptideAtlasiO95243
PRIDEiO95243
ProteomicsDBi50740
50741 [O95243-2]
50742 [O95243-3]
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
EuPathDBiHostDB:ENSG00000129071.9
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

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

ChiTaRSiMBD4 human
EvolutionaryTraceiO95243
GeneWikiiMBD4
GenomeRNAii8930
PROiPR:O95243
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129071 Expressed in 248 organ(s), highest expression level in secondary oocyte
CleanExiHS_MBD4
HS_MED1
ExpressionAtlasiO95243 baseline and differential
GenevisibleiO95243 HS

Family and domain databases

InterProiView protein in InterPro
IPR016177 DNA-bd_dom_sf
IPR011257 DNA_glycosylase
IPR017352 MBD4
IPR001739 Methyl_CpG_DNA-bd
PANTHERiPTHR15074:SF6 PTHR15074:SF6, 1 hit
PfamiView protein in Pfam
PF01429 MBD, 1 hit
PIRSFiPIRSF038005 Methyl_CpG_bd_MBD4, 1 hit
SMARTiView protein in SMART
SM00391 MBD, 1 hit
SUPFAMiSSF48150 SSF48150, 1 hit
SSF54171 SSF54171, 1 hit
PROSITEiView protein in PROSITE
PS50982 MBD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMBD4_HUMAN
AccessioniPrimary (citable) accession number: O95243
Secondary accession number(s): B4DZN2
, D3DNC3, D3DNC4, E9PEE4, Q2MD36, Q7Z4T3, Q96F09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 152 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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