MUTYH_MOUSE
ID MUTYH_MOUSE Reviewed; 515 AA.
AC Q99P21; A2AGE3;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Adenine DNA glycosylase;
DE EC=3.2.2.31 {ECO:0000269|PubMed:11160897};
DE AltName: Full=MutY homolog;
DE Short=mMYH;
GN Name=Mutyh; Synonyms=Myh;
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 [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11160897; DOI=10.1093/nar/29.3.743;
RA Yang H., Clendenin W.M., Wong D., Demple B., Slupska M.M., Chiang J.-H.,
RA Miller J.H.;
RT "Enhanced activity of adenine-DNA glycosylase (Myh) by
RT apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair
RT of an A/GO mismatch.";
RL Nucleic Acids Res. 29:743-752(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14742662; DOI=10.1093/nar/gkh214;
RA Ichinoe A., Behmanesh M., Tominaga Y., Ushijima Y., Hirano S., Sakai Y.,
RA Tsuchimoto D., Sakumi K., Wake N., Nakabeppu Y.;
RT "Identification and characterization of two forms of mouse MUTYH proteins
RT encoded by alternatively spliced transcripts.";
RL Nucleic Acids Res. 32:477-487(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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).
CC -!- FUNCTION: Involved in oxidative DNA damage repair. Initiates repair of
CC A*oxoG to C*G by removing the inappropriately paired adenine base from
CC the DNA backbone. Possesses both adenine and 2-OH-A DNA glycosylase
CC activities. {ECO:0000269|PubMed:11160897, ECO:0000269|PubMed:14742662}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes free adenine bases from 7,8-dihydro-8-
CC oxoguanine:adenine mismatched double-stranded DNA, leaving an
CC apurinic site.; EC=3.2.2.31; Evidence={ECO:0000269|PubMed:11160897};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a
CC role in catalysis, but is probably involved in the proper positioning
CC of the enzyme along the DNA strand. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14742662}.
CC Mitochondrion {ECO:0000269|PubMed:14742662}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, liver, intestine, brain
CC and thymus. {ECO:0000269|PubMed:14742662}.
CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000305}.
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DR EMBL; AY007717; AAG16632.1; -; mRNA.
DR EMBL; AB117938; BAC98380.1; -; mRNA.
DR EMBL; AL683847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057942; AAH57942.1; -; mRNA.
DR CCDS; CCDS18518.1; -.
DR RefSeq; NP_001153053.1; NM_001159581.1.
DR RefSeq; NP_573513.2; NM_133250.2.
DR PDB; 7EF8; X-ray; 2.45 A; A=35-487.
DR PDB; 7EF9; X-ray; 1.97 A; A=45-487.
DR PDB; 7EFA; X-ray; 2.70 A; B=331-515.
DR PDBsum; 7EF8; -.
DR PDBsum; 7EF9; -.
DR PDBsum; 7EFA; -.
DR AlphaFoldDB; Q99P21; -.
DR SMR; Q99P21; -.
DR BioGRID; 214159; 3.
DR STRING; 10090.ENSMUSP00000099760; -.
DR PhosphoSitePlus; Q99P21; -.
DR EPD; Q99P21; -.
DR jPOST; Q99P21; -.
DR MaxQB; Q99P21; -.
DR PaxDb; Q99P21; -.
DR PRIDE; Q99P21; -.
DR ProteomicsDB; 252617; -.
DR Ensembl; ENSMUST00000102699; ENSMUSP00000099760; ENSMUSG00000028687.
DR GeneID; 70603; -.
DR KEGG; mmu:70603; -.
DR UCSC; uc008uhm.2; mouse.
DR CTD; 4595; -.
DR MGI; MGI:1917853; Mutyh.
DR VEuPathDB; HostDB:ENSMUSG00000028687; -.
DR eggNOG; KOG2457; Eukaryota.
DR GeneTree; ENSGT00510000047220; -.
DR HOGENOM; CLU_012862_0_0_1; -.
DR InParanoid; Q99P21; -.
DR OMA; THIRLKM; -.
DR OrthoDB; 616758at2759; -.
DR PhylomeDB; Q99P21; -.
DR TreeFam; TF328549; -.
DR Reactome; R-MMU-110331; Cleavage of the damaged purine.
DR Reactome; R-MMU-110357; Displacement of DNA glycosylase by APEX1.
DR BioGRID-ORCS; 70603; 3 hits in 109 CRISPR screens.
DR ChiTaRS; Mutyh; mouse.
DR PRO; PR:Q99P21; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q99P21; protein.
DR Bgee; ENSMUSG00000028687; Expressed in embryonic post-anal tail and 132 other tissues.
DR ExpressionAtlas; Q99P21; baseline and differential.
DR Genevisible; Q99P21; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0034039; F:8-oxo-7,8-dihydroguanine DNA N-glycosylase activity; IBA:GO_Central.
DR GO; GO:0035485; F:adenine/guanine mispair binding; IBA:GO_Central.
DR GO; GO:0019104; F:DNA N-glycosylase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032407; F:MutSalpha complex binding; ISO:MGI.
DR GO; GO:0032357; F:oxidized purine DNA binding; IBA:GO_Central.
DR GO; GO:0000701; F:purine-specific mismatch base pair DNA N-glycosylase activity; ISS:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; TAS:MGI.
DR GO; GO:0006298; P:mismatch repair; IBA:GO_Central.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IMP:CACAO.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR CDD; cd03431; DNA_Glycosylase_C; 1.
DR CDD; cd00056; ENDO3c; 1.
DR Gene3D; 1.10.1670.10; -; 1.
DR InterPro; IPR011257; DNA_glycosylase.
DR InterPro; IPR004036; Endonuclease-III-like_CS2.
DR InterPro; IPR003651; Endonuclease3_FeS-loop_motif.
DR InterPro; IPR004035; Endouclease-III_FeS-bd_BS.
DR InterPro; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR000445; HhH_motif.
DR InterPro; IPR044298; MIG/MutY.
DR InterPro; IPR029119; MutY_C.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR PANTHER; PTHR42944; PTHR42944; 1.
DR Pfam; PF10576; EndIII_4Fe-2S; 1.
DR Pfam; PF00633; HHH; 1.
DR Pfam; PF00730; HhH-GPD; 1.
DR Pfam; PF14815; NUDIX_4; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SMART; SM00525; FES; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS00764; ENDONUCLEASE_III_1; 1.
DR PROSITE; PS01155; ENDONUCLEASE_III_2; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; DNA damage; DNA repair; Glycosidase; Hydrolase; Iron;
KW Iron-sulfur; Metal-binding; Mitochondrion; Nucleus; Reference proteome.
FT CHAIN 1..515
FT /note="Adenine DNA glycosylase"
FT /id="PRO_0000102240"
FT DOMAIN 335..466
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 468..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 376..398
FT /note="Nudix box"
FT COMPBIAS 1..26
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 476..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 105
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT BINDING 261
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 268
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 271
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 277
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT SITE 207
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT CONFLICT 5
FT /note="Q -> R (in Ref. 4; AAH57942)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="Q -> E (in Ref. 1; AAG16632 and 4; AAH57942)"
FT /evidence="ECO:0000305"
FT CONFLICT 312..313
FT /note="TS -> PP (in Ref. 1; AAG16632 and 4; AAH57942)"
FT /evidence="ECO:0000305"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 61..78
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 94..108
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 113..126
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 130..134
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:7EF9"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:7EF8"
FT HELIX 152..167
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 176..182
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 188..199
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 208..217
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 227..240
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 246..259
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:7EF8"
FT HELIX 319..325
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 336..347
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 355..360
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:7EF9"
FT TURN 366..369
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 387..397
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 402..404
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 406..414
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 416..428
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 441..444
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 446..450
FT /evidence="ECO:0007829|PDB:7EF9"
FT STRAND 452..454
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 456..468
FT /evidence="ECO:0007829|PDB:7EF9"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:7EFA"
SQ SEQUENCE 515 AA; 57723 MW; 10DC39CC3A01AE5B CRC64;
MKKLQASVRS HKKQPANHKR RRTRALSSSQ AKPSSLDGLA KQKREELLQA SVSPYHLFSD
VADVTAFRSN LLSWYDQEKR DLPWRNLAKE EANSDRRAYA VWVSEVMLQQ TQVATVIDYY
TRWMQKWPKL QDLASASLEE VNQLWSGLGY YSRGRRLQEG ARKVVEELGG HMPRTAETLQ
QLLPGVGRYT AGAIASIAFD QVTGVVDGNV LRVLCRVRAI GADPTSTLVS HHLWNLAQQL
VDPARPGDFN QAAMELGATV CTPQRPLCSH CPVQSLCRAY QRVQRGQLSA LPGRPDIEEC
ALNTRQCQLC LTSSSPWDPS MGVANFPRKA SRRPPREEYS ATCVVEQPGA IGGPLVLLVQ
RPDSGLLAGL WEFPSVTLEP SEQHQHKALL QELQRWCGPL PAIRLQHLGE VIHIFSHIKL
TYQVYSLALD QAPASTAPPG ARWLTWEEFC NAAVSTAMKK VFRMYEDHRQ GTRKGSKRSQ
VCPPSSRKKP SLGQQVLDTF FQRHIPTDKP NSTTQ
