ID MBD4_HUMAN Reviewed; 580 AA. AC O95243; Q7Z4T3; Q96F09; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 07-JUL-2009, entry version 70. DE RecName: Full=Methyl-CpG-binding domain protein 4; DE EC=3.2.2.-; DE AltName: Full=Methyl-CpG-binding protein MBD4; DE AltName: Full=Methyl-CpG-binding endonuclease 1; DE AltName: Full=Mismatch-specific DNA N-glycosylase; GN Name=MBD4; Synonyms=MED1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=98449942; PubMed=9774669; RA Hendrich B., Bird A.; RT "Identification and characterization of a family of mammalian methyl- RT CpG binding proteins."; RL Mol. Cell. Biol. 18:6538-6547(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=99373255; PubMed=10441743; DOI=10.1007/s003359901112; RA Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A.; RT "Genomic structure and chromosomal mapping of the murine and human RT mbd1, mbd2, mbd3, and mbd4 genes."; RL Mamm. Genome 10:906-912(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH RP MLH1. RC TISSUE=Fetal brain; RX MEDLINE=99199294; PubMed=10097147; DOI=10.1073/pnas.96.7.3969; RA Bellacosa A., Cicchillitti L., Schepis F., Riccio A., Yeung A.T., RA Matsumoto Y., Golemis E.A., Genuardi M., Neri G.; RT "MED1, a novel human methyl-CpG-binding endonuclease, interacts with RT DNA mismatch repair protein MLH1."; RL Proc. Natl. Acad. Sci. U.S.A. 96:3969-3974(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Lung; RA Guo J.H., Chen L., Yu L.; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-273; PRO-342; RP LYS-346 AND HIS-568. RG NIEHS SNPs program; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION. RX MEDLINE=20490664; PubMed=10930409; DOI=10.1074/jbc.M004535200; RA Petronzelli F., Riccio A., Markham G.D., Seeholzer S.H., Stoerker J., RA Genuardi M., Yeung A.T., Matsumoto Y., Bellacosa A.; RT "Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a RT mismatch-specific DNA N-glycosylase."; RL J. Biol. Chem. 275:32422-32429(2000). RN [9] RP INTERACTION WITH FADD. RX MEDLINE=22608636; PubMed=12702765; DOI=10.1073/pnas.0431215100; RA Screaton R.A., Kiessling S., Sansom O.J., Millar C.B., Maddison K., RA Bird A., Clarke A.R., Frisch S.M.; RT "Fas-associated death domain protein interacts with methyl-CpG binding RT domain protein 4: a potential link between genome surveillance and RT apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:5211-5216(2003). CC -!- FUNCTION: Mismatch-specific DNA N-glycosylase involved in DNA CC repair. Has thymine glycosylase activity and is specific for G:T CC mismatches within methylated and unmethylated CpG sites. Can also CC remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase CC activity. Was first identified as methyl-CpG-binding protein. CC -!- SUBUNIT: Interacts with MLH1. CC -!- INTERACTION: CC P67870:CSNK2B; NbExp=1; IntAct=EBI-348011, EBI-348169; CC Q13158:FADD; NbExp=5; IntAct=EBI-348011, EBI-494804; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O95243-1; Sequence=Displayed; CC Name=2; CC IsoId=O95243-2; Sequence=VSP_010816; CC Note=No experimental confirmation available; CC Name=3; CC IsoId=O95243-3; Sequence=VSP_010817, VSP_010818; CC Note=No experimental confirmation available; CC -!- SIMILARITY: Contains 1 MBD (methyl-CpG-binding) domain. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mbd4/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF072250; AAC68879.1; -; mRNA. DR EMBL; AF120999; AAD50374.1; -; Genomic_DNA. DR EMBL; AF120997; AAD50374.1; JOINED; Genomic_DNA. DR EMBL; AF120998; AAD50374.1; JOINED; Genomic_DNA. DR EMBL; AF114784; AAD22195.1; -; mRNA. DR EMBL; AF532602; AAP97338.1; -; mRNA. DR EMBL; CR450305; CAG29301.1; -; mRNA. DR EMBL; AF494057; AAM00008.1; -; Genomic_DNA. DR EMBL; BC011752; AAH11752.1; -; mRNA. DR IPI; IPI00426727; -. DR IPI; IPI00426728; -. DR IPI; IPI00426729; -. DR RefSeq; NP_003916.1; -. DR UniGene; Hs.35947; -. DR HSSP; Q9Z2D7; 1NGN. DR SMR; O95243; 437-580. DR IntAct; O95243; 2. DR PhosphoSite; O95243; -. DR PRIDE; O95243; -. DR Ensembl; ENSG00000129071; Homo sapiens. DR GeneID; 8930; -. DR KEGG; hsa:8930; -. DR UCSC; uc003emh.1; human. DR UCSC; uc003emi.1; human. DR UCSC; uc003emj.1; human. DR GeneCards; GC03M130632; -. DR H-InvDB; HIX0003669; -. DR HGNC; HGNC:6919; MBD4. DR HPA; HPA002031; -. DR MIM; 603574; gene. DR PharmGKB; PA30663; -. DR HOGENOM; O95243; -. DR HOVERGEN; O95243; -. DR OMA; O95243; YLHKNGE. DR Reactome; REACT_216; DNA Repair. DR NextBio; 33578; -. DR ArrayExpress; O95243; -. DR Bgee; O95243; -. DR CleanEx; HS_MBD4; -. DR CleanEx; HS_MED1; -. DR GermOnline; ENSG00000129071; Homo sapiens. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0004520; F:endodeoxyribonuclease activity; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0003696; F:satellite DNA binding; TAS:ProtInc. DR GO; GO:0045008; P:depyrimidination; EXP:Reactome. DR InterPro; IPR003265; HhH-GPD_domain. DR InterPro; IPR017352; Methyl_CpG-bd_MBD4. DR InterPro; IPR001739; Methyl_CpG_DNA-bd. DR Gene3D; G3DSA:3.30.890.10; Methyl_CpG_DNA-bd; 1. DR Pfam; PF00730; HhH-GPD; 1. DR Pfam; PF01429; MBD; 1. DR PIRSF; PIRSF038005; Methyl_CpG_bd_MBD4; 1. DR SMART; SM00391; MBD; 1. DR PROSITE; PS50982; MBD; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; DNA damage; DNA repair; KW DNA-binding; Hydrolase; Nucleus; Polymorphism. FT CHAIN 1 580 Methyl-CpG-binding domain protein 4. FT /FTId=PRO_0000096264. FT DOMAIN 76 148 MBD. FT ACT_SITE 560 560 By similarity. FT VAR_SEQ 395 400 Missing (in isoform 2). FT /FTId=VSP_010816. FT VAR_SEQ 539 540 KY -> AP (in isoform 3). FT /FTId=VSP_010817. FT VAR_SEQ 541 580 Missing (in isoform 3). FT /FTId=VSP_010818. FT VARIANT 61 61 C -> R (in dbSNP:rs2307296). FT /FTId=VAR_029306. FT VARIANT 273 273 A -> S (in dbSNP:rs10342). FT /FTId=VAR_019357. FT VARIANT 273 273 A -> T (in dbSNP:rs10342). FT /FTId=VAR_019514. FT VARIANT 342 342 S -> P (in dbSNP:rs2307289). FT /FTId=VAR_019358. FT VARIANT 346 346 E -> K (in dbSNP:rs140693). FT /FTId=VAR_019359. FT VARIANT 358 358 I -> T (in dbSNP:rs2307298). FT /FTId=VAR_019515. FT VARIANT 568 568 D -> H (in dbSNP:rs2307293). FT /FTId=VAR_019360. SQ SEQUENCE 580 AA; 66051 MW; BF16FB21A34B8E5F CRC64; MGTTGLESLS LGDRGAAPTV TSSERLVPDP PNDLRKEDVA MELERVGEDE EQMMIKRSSE CNPLLQEPIA SAQFGATAGT ECRKSVPCGW ERVVKQRLFG KTAGRFDVYF ISPQGLKFRS KSSLANYLHK NGETSLKPED FDFTVLSKRG IKSRYKDCSM AALTSHLQNQ SNNSNWNLRT RSKCKKDVFM PPSSSSELQE SRGLSNFTST HLLLKEDEGV DDVNFRKVRK PKGKVTILKG IPIKKTKKGC RKSCSGFVQS DSKRESVCNK ADAESEPVAQ KSQLDRTVCI SDAGACGETL SVTSEENSLV KKKERSLSSG SNFCSEQKTS GIINKFCSAK DSEHNEKYED TFLESEEIGT KVEVVERKEH LHTDILKRGS EMDNNCSPTR KDFTGEKIFQ EDTIPRTQIE RRKTSLYFSS KYNKEALSPP RRKAFKKWTP PRSPFNLVQE TLFHDPWKLL IATIFLNRTS GKMAIPVLWK FLEKYPSAEV ARTADWRDVS ELLKPLGLYD LRAKTIVKFS DEYLTKQWKY PIELHGIGKY GNDSYRIFCV NEWKQVHPED HKLNKYHDWL WENHEKLSLS //