MBD4_MOUSE
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 25-MAY-2022, entry version 151.
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.
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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; Q9Z2D7; -.
DR PeptideAtlas; Q9Z2D7; -.
DR PRIDE; Q9Z2D7; -.
DR ProteomicsDB; 295802; -.
DR DNASU; 17193; -.
DR GeneID; 17193; -.
DR KEGG; mmu:17193; -.
DR UCSC; uc009dje.2; mouse.
DR CTD; 8930; -.
DR MGI; MGI:1333850; Mbd4.
DR eggNOG; KOG4161; Eukaryota.
DR InParanoid; Q9Z2D7; -.
DR OrthoDB; 1574293at2759; -.
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 114 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:cellular response to DNA damage stimulus; 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 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; PTHR15074; 2.
DR Pfam; PF01429; MBD; 1.
DR PIRSF; PIRSF038005; Methyl_CpG_bd_MBD4; 1.
DR SMART; SM00391; MBD; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
DR SUPFAM; SSF54171; SSF54171; 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
