ID MBD4_MOUSE Reviewed; 554 AA. AC Q9Z2D7; Q792D2; Q8R3R3; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 08-NOV-2023, entry version 156. 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=Mismatch-specific DNA N-glycosylase; GN Name=Mbd4; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=9774669; DOI=10.1128/mcb.18.11.6538; RA Hendrich B., Bird A.; RT "Identification and characterization of a family of mammalian methyl-CpG RT binding proteins."; RL Mol. Cell. Biol. 18:6538-6547(1998). RN [2] RP NUCLEOTIDE SEQUENCE. RC STRAIN=129; RX 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 mbd1, RT mbd2, mbd3, and mbd4 genes."; RL Mamm. Genome 10:906-912(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 411-554. RX PubMed=12456671; DOI=10.1074/jbc.m210884200; RA Wu P., Qiu C., Sohail A., Zhang X., Bhagwat A.S., Cheng X.; RT "Mismatch repair in methylated DNA. Structure and activity of the mismatch- RT specific thymine glycosylase domain of methyl-CpG-binding protein MBD4."; RL J. Biol. Chem. 278:5285-5291(2003). CC -!- FUNCTION: Mismatch-specific DNA N-glycosylase involved in DNA repair. CC Has thymine glycosylase activity and is specific for G:T mismatches CC within methylated and unmethylated CpG sites. Can also remove uracil or CC 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first CC identified as methyl-CpG-binding protein. {ECO:0000269|PubMed:9774669}. CC -!- SUBUNIT: Interacts with MLH1. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9774669}. CC Note=Nuclear, in discrete foci. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF072249; AAC68878.1; -; mRNA. DR EMBL; AF120996; AAD56595.1; -; Genomic_DNA. DR EMBL; BC024812; AAH24812.1; -; mRNA. DR CCDS; CCDS39603.1; -. DR RefSeq; NP_034904.2; NM_010774.2. DR PDB; 1NGN; X-ray; 2.10 A; A=400-554. DR PDB; 3VXV; X-ray; 2.00 A; A=69-136. DR PDB; 3VXX; X-ray; 2.20 A; A=69-136. DR PDB; 3VYB; X-ray; 2.40 A; A=69-136. DR PDB; 3VYQ; X-ray; 2.52 A; A/D=63-136. DR PDB; 4EVV; X-ray; 2.39 A; A=411-554. DR PDB; 4EW0; X-ray; 2.39 A; A=411-554. DR PDB; 4EW4; X-ray; 2.79 A; A=411-554. DR PDBsum; 1NGN; -. DR PDBsum; 3VXV; -. DR PDBsum; 3VXX; -. DR PDBsum; 3VYB; -. DR PDBsum; 3VYQ; -. DR PDBsum; 4EVV; -. DR PDBsum; 4EW0; -. DR PDBsum; 4EW4; -. DR AlphaFoldDB; Q9Z2D7; -. DR SMR; Q9Z2D7; -. DR BioGRID; 201333; 2. DR STRING; 10090.ENSMUSP00000032469; -. DR iPTMnet; Q9Z2D7; -. DR PhosphoSitePlus; Q9Z2D7; -. DR MaxQB; Q9Z2D7; -. DR PaxDb; 10090-ENSMUSP00000032469; -. DR PeptideAtlas; Q9Z2D7; -. DR ProteomicsDB; 295802; -. DR DNASU; 17193; -. DR GeneID; 17193; -. DR KEGG; mmu:17193; -. DR UCSC; uc009dje.2; mouse. DR AGR; MGI:1333850; -. DR CTD; 8930; -. DR MGI; MGI:1333850; Mbd4. DR eggNOG; KOG4161; Eukaryota. DR InParanoid; Q9Z2D7; -. DR OrthoDB; 1451962at2759; -. DR PhylomeDB; Q9Z2D7; -. DR TreeFam; TF329176; -. DR Reactome; R-MMU-110329; Cleavage of the damaged pyrimidine. DR Reactome; R-MMU-110357; Displacement of DNA glycosylase by APEX1. DR BioGRID-ORCS; 17193; 1 hit in 120 CRISPR screens. DR ChiTaRS; Mbd4; mouse. DR EvolutionaryTrace; Q9Z2D7; -. DR PRO; PR:Q9Z2D7; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q9Z2D7; Protein. DR GO; GO:0000785; C:chromatin; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0016607; C:nuclear speck; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0008263; F:pyrimidine-specific mismatch base pair DNA N-glycosylase activity; ISO:MGI. DR GO; GO:0006974; P:DNA damage response; IMP:MGI. DR GO; GO:0006306; P:DNA methylation; TAS:MGI. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:MGI. DR GO; GO:0009314; P:response to radiation; IMP:MGI. DR CDD; cd01396; MeCP2_MBD; 1. DR IDEAL; IID50108; -. DR InterPro; IPR016177; DNA-bd_dom_sf. DR InterPro; IPR011257; DNA_glycosylase. DR InterPro; IPR017352; MBD4. DR InterPro; IPR045138; MeCP2/MBD4. DR InterPro; IPR001739; Methyl_CpG_DNA-bd. DR PANTHER; PTHR15074:SF7; METHYL-CPG-BINDING DOMAIN PROTEIN 4; 1. DR PANTHER; PTHR15074; METHYL-CPG-BINDING PROTEIN; 1. DR Pfam; PF01429; MBD; 1. DR PIRSF; PIRSF038005; Methyl_CpG_bd_MBD4; 1. DR SMART; SM00391; MBD; 1. DR SUPFAM; SSF54171; DNA-binding domain; 1. DR SUPFAM; SSF48150; DNA-glycosylase; 1. DR PROSITE; PS50982; MBD; 1. PE 1: Evidence at protein level; KW 3D-structure; DNA damage; DNA repair; DNA-binding; Hydrolase; Nucleus; KW Phosphoprotein; Reference proteome. FT CHAIN 1..554 FT /note="Methyl-CpG-binding domain protein 4" FT /id="PRO_0000096265" FT DOMAIN 63..135 FT /note="MBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 154..195 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 209..252 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 176..195 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 534 FT /evidence="ECO:0000250" FT MOD_RES 296 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O95243" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O95243" FT CONFLICT 129 FT /note="N -> D (in Ref. 3; AAH24812)" FT /evidence="ECO:0000305" FT STRAND 78..83 FT /evidence="ECO:0007829|PDB:3VXV" FT TURN 88..91 FT /evidence="ECO:0007829|PDB:3VXV" FT STRAND 93..98 FT /evidence="ECO:0007829|PDB:3VXV" FT STRAND 104..107 FT /evidence="ECO:0007829|PDB:3VYQ" FT HELIX 108..118 FT /evidence="ECO:0007829|PDB:3VXV" FT HELIX 125..127 FT /evidence="ECO:0007829|PDB:3VXV" FT HELIX 423..426 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 430..440 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 445..458 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 462..467 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 470..476 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 478..480 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 483..499 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 505..507 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 513..522 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 527..529 FT /evidence="ECO:0007829|PDB:1NGN" FT HELIX 535..551 FT /evidence="ECO:0007829|PDB:1NGN" SQ SEQUENCE 554 AA; 62578 MW; 792D37CB180291F5 CRC64; MESPNLGDNR VRGESLVPDP PWDRCKEDIA VGLGGVGEDG KDLVISSERS SLLQEPTAST LSSTTATEGH KPVPCGWERV VKQRLSGKTA GKFDVYFISP QGLKFRSKRS LANYLLKNGE TFLKPEDFNF TVLPKGSINP GYKHQSLAAL TSLQPNETDV SKQNLKTRSK WKTDVLPLPS GTSESPESSG LSNSNSACLL LREHRDIQDV DSEKRRKSKR KVTVLKGTAS QKTKQKCRKS LLESTQRNRK RASVVQKVGA DRELVPQESQ LNRTLCPADA CARETVGLAG EEKSPSPGLD LCFIQVTSGT TNKFHSTEAA GEANREQTFL ESEEIRSKGD RKGEAHLHTG VLQDGSEMPS CSQAKKHFTS ETFQEDSIPR TQVEKRKTSL YFSSKYNKEA LSPPRRKSFK KWTPPRSPFN LVQEILFHDP WKLLIATIFL NRTSGKMAIP VLWEFLEKYP SAEVARAADW RDVSELLKPL GLYDLRAKTI IKFSDEYLTK QWRYPIELHG IGKYGNDSYR IFCVNEWKQV HPEDHKLNKY HDWLWENHEK LSLS //