MUTYH_HUMAN
ID MUTYH_HUMAN Reviewed; 546 AA.
AC Q9UIF7; D3DPZ4; Q15830; Q9UBP2; Q9UBS7; Q9UIF4; Q9UIF5; Q9UIF6;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Adenine DNA glycosylase;
DE EC=3.2.2.31 {ECO:0000269|PubMed:20418187};
DE AltName: Full=MutY homolog;
DE Short=hMYH;
GN Name=MUTYH; Synonyms=MYH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA-3).
RX PubMed=8682794; DOI=10.1128/jb.178.13.3885-3892.1996;
RA Slupska M.M., Baikalov C., Luther W.M., Chiang J.H., Wei Y.F., Miller J.H.;
RT "Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY
RT gene whose function is required for the repair of oxidative DNA damage.";
RL J. Bacteriol. 178:3885-3892(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1; ALPHA-2; ALPHA-3; BETA-1;
RP GAMMA-2 AND GAMMA-3), AND FUNCTION.
RX PubMed=10684930; DOI=10.1093/nar/28.6.1355;
RA Ohtsubo T., Nishioka K., Imaiso Y., Iwai S., Shimokawa H., Oda H.,
RA Fujikawa T., Nakabeppu Y.;
RT "Identification of human MutY homolog (hMYH) as a repair enzyme for 2-
RT hydroxyadenine in DNA and detection of multiple forms of hMYH located in
RT nuclei and mitochondria.";
RL Nucleic Acids Res. 28:1355-1364(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-22; HIS-335; GLU-500;
RP MET-526 AND GLN-531.
RG NIEHS SNPs program;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-3).
RC TISSUE=Kidney;
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 [8]
RP STRUCTURE BY NMR OF 356-497.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the NUDIX domain from human A/G-specific adenine DNA
RT glycosylase alpha-3 splice isoform.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [9]
RP VARIANTS FAP2 CYS-176 AND ASP-393.
RX PubMed=11818965; DOI=10.1038/ng828;
RA Al-Tassan N., Chmiel N.H., Maynard J., Fleming N., Livingston A.L.,
RA Williams G.T., Hodges A.K., Davies D.R., David S.S., Sampson J.R.,
RA Cheadle J.P.;
RT "Inherited variants of MYH associated with somatic G:C-->T:A mutations in
RT colorectal tumors.";
RL Nat. Genet. 30:227-232(2002).
RN [10]
RP VARIANTS FAP2 ARG-128; CYS-176 AND ASP-393.
RX PubMed=12853198; DOI=10.1016/s0140-6736(03)13805-6;
RA Sampson J.R., Dolwani S., Jones S., Eccles D., Ellis A., Evans D.G.,
RA Frayling I., Jordan S., Maher E.R., Mak T., Maynard J., Pigatto F.,
RA Shaw J., Cheadle J.P.;
RT "Autosomal recessive colorectal adenomatous polyposis due to inherited
RT mutations of MYH.";
RL Lancet 362:39-41(2003).
RN [11]
RP VARIANTS FAP2 CYS-176 AND ASP-393, AND VARIANTS MET-22; HIS-335 AND
RP PHE-512.
RX PubMed=12606733; DOI=10.1056/nejmoa025283;
RA Sieber O.M., Lipton L., Crabtree M., Heinimann K., Fidalgo P.,
RA Phillips R.K.S., Bisgaard M.-L., Orntoft T.F., Aaltonen L.A., Hodgson S.V.,
RA Thomas H.J.W., Tomlinson I.P.M.;
RT "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line
RT mutations in MYH.";
RL N. Engl. J. Med. 348:791-799(2003).
RN [12]
RP VARIANTS FAP2 HIS-125; HIS-179 AND TRP-238.
RX PubMed=15366000; DOI=10.1002/humu.9282;
RA Isidro G., Laranjeira F., Pires A., Leite J., Regateiro F.,
RA Castro e Sousa F., Soares J., Castro C., Giria J., Brito M.J., Medeira A.,
RA Teixeira R., Morna H., Gaspar I., Marinho C., Jorge R., Brehm A.,
RA Ramos J.S., Boavida M.G.;
RT "Germline MUTYH (MYH) mutations in Portuguese individuals with multiple
RT colorectal adenomas.";
RL Hum. Mutat. 24:353-354(2004).
RN [13]
RP VARIANTS GASC SER-402 AND ARG-411.
RX PubMed=15273732; DOI=10.1038/sj.onc.1207574;
RA Kim C.J., Cho Y.G., Park C.H., Kim S.Y., Nam S.W., Lee S.H., Yoo N.J.,
RA Lee J.Y., Park W.S.;
RT "Genetic alterations of the MYH gene in gastric cancer.";
RL Oncogene 23:6820-6822(2004).
RN [14]
RP VARIANTS FAP2 CYS-176; HIS-242; TRP-271; PRO-385; ASP-393; CYS-423 AND
RP GLU-477 DEL, AND VARIANTS MET-22 AND HIS-335.
RX PubMed=16134147; DOI=10.1002/humu.9370;
RA Aceto G., Curia M.C., Veschi S., De Lellis L., Mammarella S., Catalano T.,
RA Stuppia L., Palka G., Valanzano R., Tonelli F., Casale V., Stigliano V.,
RA Cetta F., Battista P., Mariani-Costantini R., Cama A.;
RT "Mutations of APC and MYH in unrelated Italian patients with adenomatous
RT polyposis coli.";
RL Hum. Mutat. 26:394-394(2005).
RN [15]
RP VARIANTS FAP2 CYS-176; SER-177; VAL-280; LEU-292; PRO-385 AND ASP-393, AND
RP VARIANTS MET-22; HIS-335 AND PHE-512.
RX PubMed=16941501; DOI=10.1002/humu.9460;
RG PAFNORD Group;
RA Lejeune S., Guillemot F., Triboulet J.P., Cattan S., Mouton C., Porchet N.,
RA Manouvrier S., Buisine M.P.;
RT "Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in
RT patients with multiple polyposis.";
RL Hum. Mutat. 27:1064-1064(2006).
RN [16]
RP VARIANTS FAP2 ILE-TRP-148 INS; CYS-176; GLN-182; VAL-220; HIS-242 AND
RP ASP-393, AND VARIANTS MET-22 AND HIS-335.
RX PubMed=16287072; DOI=10.1002/ijc.21470;
RA Russell A.M., Zhang J., Luz J., Hutter P., Chappuis P.O., Berthod C.R.,
RA Maillet P., Mueller H., Heinimann K.;
RT "Prevalence of MYH germline mutations in Swiss APC mutation-negative
RT polyposis patients.";
RL Int. J. Cancer 118:1937-1940(2006).
RN [17]
RP VARIANTS FAP2 LEU-154; CYS-176; HIS-179; HIS-242; TRP-271; LEU-292;
RP CYS-306; ASP-393; LEU-402; CYS-423; GLU-477 DEL AND PHE-490.
RX PubMed=16557584; DOI=10.1002/ijc.21905;
RA Aretz S., Uhlhaas S., Goergens H., Siberg K., Vogel M., Pagenstecher C.,
RA Mangold E., Caspari R., Propping P., Friedl W.;
RT "MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations
RT present with an attenuated or atypical phenotype.";
RL Int. J. Cancer 119:807-814(2006).
RN [18]
RP VARIANTS FAP2 CYS-176; CYS-179; TRP-182 AND ASP-393.
RX PubMed=18091433; DOI=10.1097/gim.0b013e31815bf940;
RA Cattaneo F., Molatore S., Mihalatos M., Apessos A., Venesio T., Bione S.,
RA Grignani P., Nasioulas G., Ranzani G.N.;
RT "Heterogeneous molecular mechanisms underlie attenuated familial
RT adenomatous polyposis.";
RL Genet. Med. 9:836-841(2007).
RN [19]
RP VARIANTS FAP2 GLU-213; SER-235 AND MET-474.
RX PubMed=18515411; DOI=10.1136/gut.2007.145748;
RA Dallosso A.R., Dolwani S., Jones N., Jones S., Colley J., Maynard J.,
RA Idziaszczyk S., Humphreys V., Arnold J., Donaldson A., Eccles D., Ellis A.,
RA Evans D.G., Frayling I.M., Hes F.J., Houlston R.S., Maher E.R., Nielsen M.,
RA Parry S., Tyler E., Moskvina V., Cheadle J.P., Sampson J.R.;
RT "Inherited predisposition to colorectal adenomas caused by multiple rare
RT alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3.";
RL Gut 57:1252-1255(2008).
RN [20]
RP CHARACTERIZATION OF VARIANTS FAP2 ILE-TRP-148 INS; CYS-176; TRP-182;
RP ASP-393 AND GLU-477 DEL, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20418187; DOI=10.1016/j.dnarep.2010.03.008;
RA D'Agostino V.G., Minoprio A., Torreri P., Marinoni I., Bossa C.,
RA Petrucci T.C., Albertini A.M., Ranzani G.N., Bignami M., Mazzei F.;
RT "Functional analysis of MUTYH mutated proteins associated with familial
RT adenomatous polyposis.";
RL DNA Repair 9:700-707(2010).
RN [21]
RP VARIANTS FAP2 ILE-TRP-148 INS; TRP-182 AND GLU-477 DEL, AND
RP CHARACTERIZATION OF VARIANTS FAP2 ILE-TRP-148 INS; CYS-176; TRP-182;
RP ASP-393 AND GLU-477 DEL.
RX PubMed=19953527; DOI=10.1002/humu.21158;
RA Molatore S., Russo M.T., D'Agostino V.G., Barone F., Matsumoto Y.,
RA Albertini A.M., Minoprio A., Degan P., Mazzei F., Bignami M., Ranzani G.N.;
RT "MUTYH mutations associated with familial adenomatous polyposis: functional
RT characterization by a mammalian cell-based assay.";
RL Hum. Mutat. 31:159-166(2010).
RN [22]
RP CHARACTERIZATION OF VARIANTS FAP2 CYS-176; HIS-179; VAL-220; VAL-280;
RP CYS-306; PRO-385; ASP-393; LEU-402 AND GLU-477 DEL, CHARACTERIZATION OF
RP VARIANTS GLU-72; VAL-370 AND PHE-512, FUNCTION, AND MUTAGENESIS OF ASP-233.
RX PubMed=20848659; DOI=10.1002/humu.21363;
RA Goto M., Shinmura K., Nakabeppu Y., Tao H., Yamada H., Tsuneyoshi T.,
RA Sugimura H.;
RT "Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant
RT proteins found in patients with colorectal polyposis and cancer.";
RL Hum. Mutat. 31:E1861-E1874(2010).
RN [23]
RP CHARACTERIZATION OF VARIANTS FAP2 LEU-18; HIS-125; ARG-128; LEU-154;
RP CYS-176; CYS-179; HIS-179; GLN-182; GLU-186; VAL-220; TRP-238; HIS-242;
RP TRP-271; GLU-283; LEU-292; CYS-306; THR-377; PRO-385; ASP-393; LEU-402;
RP MET-417; CYS-423; ASP-470; THR-470; GLU-477 DEL; THR-486 AND PHE-490,
RP CHARACTERIZATION OF VARIANTS GASC SER-402 AND ARG-411, CHARACTERIZATION OF
RP VARIANTS MET-22; ASP-25; ARG-100; ASN-102; VAL-224; MET-231; CYS-242;
RP PHE-243; TRP-287; HIS-335; ARG-335; GLN-434; PRO-434; GLU-500; PHE-512;
RP LEU-513; MET-526 AND GLN-531, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25820570; DOI=10.1002/humu.22794;
RA Komine K., Shimodaira H., Takao M., Soeda H., Zhang X., Takahashi M.,
RA Ishioka C.;
RT "Functional complementation assay for 47 MUTYH variants in a MutY-disrupted
RT Escherichia coli strain.";
RL Hum. Mutat. 36:704-711(2015).
RN [24]
RP CHARACTERIZATION OF VARIANT FAP2 SER-235, CHARACTERIZATION OF VARIANT
RP ASN-102; GLY-121; MET-231; GLY-244; ASN-319; HIS-520 AND ALA-536, AND
RP FUNCTION.
RX PubMed=26694661; DOI=10.1002/humu.22949;
RA Shinmura K., Kato H., Goto M., Yamada H., Tao H., Nakamura S., Sugimura H.;
RT "Functional evaluation of nine missense-type variants of the human DNA
RT glycosylase enzyme MUTYH in the Japanese population.";
RL Hum. Mutat. 37:350-353(2016).
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:10684930, ECO:0000269|PubMed:20418187,
CC ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570,
CC ECO:0000269|PubMed:26694661}.
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:20418187};
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 -!- INTERACTION:
CC Q9UIF7-3; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-10321956, EBI-741181;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25820570}.
CC Mitochondrion {ECO:0000250|UniProtKB:Q99P21}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=Alpha-1;
CC IsoId=Q9UIF7-1; Sequence=Displayed;
CC Name=Alpha-2;
CC IsoId=Q9UIF7-2; Sequence=VSP_010549;
CC Name=Alpha-3;
CC IsoId=Q9UIF7-3; Sequence=VSP_010550;
CC Name=Beta-1;
CC IsoId=Q9UIF7-4; Sequence=VSP_010548;
CC Name=Gamma-2;
CC IsoId=Q9UIF7-5; Sequence=VSP_010548, VSP_010549;
CC Name=Gamma-3;
CC IsoId=Q9UIF7-6; Sequence=VSP_010548, VSP_010550;
CC -!- DISEASE: Familial adenomatous polyposis 2 (FAP2) [MIM:608456]: A
CC condition characterized by the development of multiple colorectal
CC adenomatous polyps, benign neoplasms derived from glandular epithelium.
CC Some affected individuals may develop colorectal carcinoma.
CC {ECO:0000269|PubMed:11818965, ECO:0000269|PubMed:12606733,
CC ECO:0000269|PubMed:12853198, ECO:0000269|PubMed:15366000,
CC ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072,
CC ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:16941501,
CC ECO:0000269|PubMed:18091433, ECO:0000269|PubMed:18515411,
CC ECO:0000269|PubMed:19953527, ECO:0000269|PubMed:20418187,
CC ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570,
CC ECO:0000269|PubMed:26694661}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which
CC starts in the stomach, can spread to the esophagus or the small
CC intestine, and can extend through the stomach wall to nearby lymph
CC nodes and organs. It also can metastasize to other parts of the body.
CC The term gastric cancer or gastric carcinoma refers to adenocarcinoma
CC of the stomach that accounts for most of all gastric malignant tumors.
CC Two main histologic types are recognized, diffuse type and intestinal
CC type carcinomas. Diffuse tumors are poorly differentiated infiltrating
CC lesions, resulting in thickening of the stomach. In contrast,
CC intestinal tumors are usually exophytic, often ulcerating, and
CC associated with intestinal metaplasia of the stomach, most often
CC observed in sporadic disease. {ECO:0000269|PubMed:15273732,
CC ECO:0000269|PubMed:25820570}. Note=The gene represented in this entry
CC may be involved in disease pathogenesis. Somatic mutations contribute
CC to the development of a sub-set of sporadic gastric cancers in carriers
CC of Helicobacter pylori (PubMed:15273732).
CC {ECO:0000269|PubMed:15273732}.
CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA89339.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA89339.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAA89345.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA89345.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/41464/mutyh-(muty-homolog-(e-coli))";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mutyh/";
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DR EMBL; U63329; AAC50618.1; -; Genomic_DNA.
DR EMBL; AB032920; BAA89336.1; -; mRNA.
DR EMBL; AB032921; BAA89337.1; -; mRNA.
DR EMBL; AB032922; BAA89338.1; -; mRNA.
DR EMBL; AB032923; BAA89339.1; ALT_SEQ; mRNA.
DR EMBL; AB032924; BAA89340.1; -; mRNA.
DR EMBL; AB032925; BAA89341.1; -; mRNA.
DR EMBL; AB032926; BAA89342.1; -; mRNA.
DR EMBL; AB032927; BAA89343.1; -; mRNA.
DR EMBL; AB032928; BAA89344.1; -; mRNA.
DR EMBL; AB032929; BAA89345.1; ALT_SEQ; mRNA.
DR EMBL; HQ205466; ADP90937.1; -; Genomic_DNA.
DR EMBL; HQ205468; ADP90947.1; -; Genomic_DNA.
DR EMBL; HQ205469; ADP90952.1; -; Genomic_DNA.
DR EMBL; HQ205470; ADP90957.1; -; Genomic_DNA.
DR EMBL; HQ205472; ADP90967.1; -; Genomic_DNA.
DR EMBL; HQ205473; ADP90972.1; -; Genomic_DNA.
DR EMBL; HQ205474; ADP90977.1; -; Genomic_DNA.
DR EMBL; HQ205475; ADP90982.1; -; Genomic_DNA.
DR EMBL; HQ205476; ADP90987.1; -; Genomic_DNA.
DR EMBL; HQ205477; ADP90992.1; -; Genomic_DNA.
DR EMBL; HQ205479; ADP91002.1; -; Genomic_DNA.
DR EMBL; HQ205480; ADP91007.1; -; Genomic_DNA.
DR EMBL; HQ205481; ADP91012.1; -; Genomic_DNA.
DR EMBL; HQ205482; ADP91017.1; -; Genomic_DNA.
DR EMBL; HQ205483; ADP91022.1; -; Genomic_DNA.
DR EMBL; HQ205484; ADP91027.1; -; Genomic_DNA.
DR EMBL; HQ205485; ADP91032.1; -; Genomic_DNA.
DR EMBL; HQ205486; ADP91037.1; -; Genomic_DNA.
DR EMBL; HQ205487; ADP91042.1; -; Genomic_DNA.
DR EMBL; HQ205488; ADP91047.1; -; Genomic_DNA.
DR EMBL; HQ205489; ADP91052.1; -; Genomic_DNA.
DR EMBL; HQ205490; ADP91057.1; -; Genomic_DNA.
DR EMBL; HQ205491; ADP91062.1; -; Genomic_DNA.
DR EMBL; HQ205492; ADP91067.1; -; Genomic_DNA.
DR EMBL; HQ205493; ADP91072.1; -; Genomic_DNA.
DR EMBL; HQ205494; ADP91077.1; -; Genomic_DNA.
DR EMBL; HQ205495; ADP91082.1; -; Genomic_DNA.
DR EMBL; HQ205496; ADP91087.1; -; Genomic_DNA.
DR EMBL; HQ205497; ADP91092.1; -; Genomic_DNA.
DR EMBL; HQ205498; ADP91097.1; -; Genomic_DNA.
DR EMBL; HQ205499; ADP91102.1; -; Genomic_DNA.
DR EMBL; HQ205500; ADP91107.1; -; Genomic_DNA.
DR EMBL; HQ205501; ADP91112.1; -; Genomic_DNA.
DR EMBL; HQ205502; ADP91117.1; -; Genomic_DNA.
DR EMBL; HQ205503; ADP91122.1; -; Genomic_DNA.
DR EMBL; HQ205505; ADP91132.1; -; Genomic_DNA.
DR EMBL; AF527839; AAM78555.1; -; Genomic_DNA.
DR EMBL; AL359540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06993.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06996.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06997.1; -; Genomic_DNA.
DR EMBL; BC003178; AAH03178.1; -; mRNA.
DR CCDS; CCDS41320.1; -. [Q9UIF7-6]
DR CCDS; CCDS41321.1; -. [Q9UIF7-5]
DR CCDS; CCDS41322.1; -. [Q9UIF7-6]
DR CCDS; CCDS520.1; -. [Q9UIF7-1]
DR CCDS; CCDS72776.1; -. [Q9UIF7-4]
DR CCDS; CCDS72777.1; -. [Q9UIF7-2]
DR RefSeq; NP_001041636.1; NM_001048171.1. [Q9UIF7-6]
DR RefSeq; NP_001041637.1; NM_001048172.1. [Q9UIF7-5]
DR RefSeq; NP_001041638.1; NM_001048173.1. [Q9UIF7-6]
DR RefSeq; NP_001041639.1; NM_001048174.1. [Q9UIF7-6]
DR RefSeq; NP_001121897.1; NM_001128425.1.
DR RefSeq; NP_001280119.1; NM_001293190.1. [Q9UIF7-2]
DR RefSeq; NP_001280120.1; NM_001293191.1. [Q9UIF7-4]
DR RefSeq; NP_001280121.1; NM_001293192.1.
DR RefSeq; NP_001280124.1; NM_001293195.1. [Q9UIF7-6]
DR RefSeq; NP_001280125.1; NM_001293196.1.
DR RefSeq; NP_036354.1; NM_012222.2. [Q9UIF7-1]
DR RefSeq; XP_011539806.1; XM_011541504.2. [Q9UIF7-4]
DR RefSeq; XP_016856823.1; XM_017001334.1. [Q9UIF7-5]
DR RefSeq; XP_016856824.1; XM_017001335.1.
DR PDB; 1X51; NMR; -; A=356-497.
DR PDB; 3N5N; X-ray; 2.30 A; X/Y=76-362.
DR PDBsum; 1X51; -.
DR PDBsum; 3N5N; -.
DR AlphaFoldDB; Q9UIF7; -.
DR SMR; Q9UIF7; -.
DR BioGRID; 110681; 27.
DR DIP; DIP-41972N; -.
DR IntAct; Q9UIF7; 16.
DR MINT; Q9UIF7; -.
DR STRING; 9606.ENSP00000361170; -.
DR iPTMnet; Q9UIF7; -.
DR PhosphoSitePlus; Q9UIF7; -.
DR BioMuta; MUTYH; -.
DR DMDM; 48428272; -.
DR EPD; Q9UIF7; -.
DR jPOST; Q9UIF7; -.
DR MassIVE; Q9UIF7; -.
DR MaxQB; Q9UIF7; -.
DR PaxDb; Q9UIF7; -.
DR PeptideAtlas; Q9UIF7; -.
DR PRIDE; Q9UIF7; -.
DR ProteomicsDB; 84500; -. [Q9UIF7-1]
DR ProteomicsDB; 84501; -. [Q9UIF7-2]
DR ProteomicsDB; 84502; -. [Q9UIF7-3]
DR ProteomicsDB; 84503; -. [Q9UIF7-4]
DR ProteomicsDB; 84504; -. [Q9UIF7-5]
DR ProteomicsDB; 84505; -. [Q9UIF7-6]
DR Antibodypedia; 1869; 335 antibodies from 41 providers.
DR CPTC; Q9UIF7; 1 antibody.
DR DNASU; 4595; -.
DR Ensembl; ENST00000354383.10; ENSP00000346354.6; ENSG00000132781.20. [Q9UIF7-5]
DR Ensembl; ENST00000355498.6; ENSP00000347685.2; ENSG00000132781.20. [Q9UIF7-6]
DR Ensembl; ENST00000372098.7; ENSP00000361170.3; ENSG00000132781.20. [Q9UIF7-1]
DR Ensembl; ENST00000372104.5; ENSP00000361176.1; ENSG00000132781.20. [Q9UIF7-6]
DR Ensembl; ENST00000372110.7; ENSP00000361182.3; ENSG00000132781.20. [Q9UIF7-2]
DR Ensembl; ENST00000372115.7; ENSP00000361187.3; ENSG00000132781.20. [Q9UIF7-3]
DR Ensembl; ENST00000448481.5; ENSP00000409718.1; ENSG00000132781.20. [Q9UIF7-4]
DR Ensembl; ENST00000456914.7; ENSP00000407590.2; ENSG00000132781.20. [Q9UIF7-6]
DR Ensembl; ENST00000672818.3; ENSP00000500891.1; ENSG00000132781.20. [Q9UIF7-1]
DR GeneID; 4595; -.
DR KEGG; hsa:4595; -.
DR MANE-Select; ENST00000456914.7; ENSP00000407590.2; NM_001048174.2; NP_001041639.1. [Q9UIF7-6]
DR UCSC; uc001cnf.4; human. [Q9UIF7-1]
DR CTD; 4595; -.
DR DisGeNET; 4595; -.
DR GeneCards; MUTYH; -.
DR GeneReviews; MUTYH; -.
DR HGNC; HGNC:7527; MUTYH.
DR HPA; ENSG00000132781; Low tissue specificity.
DR MalaCards; MUTYH; -.
DR MIM; 604933; gene.
DR MIM; 608456; phenotype.
DR MIM; 613659; phenotype.
DR neXtProt; NX_Q9UIF7; -.
DR OpenTargets; ENSG00000132781; -.
DR Orphanet; 247798; MUTYH-related attenuated familial adenomatous polyposis.
DR PharmGKB; PA31328; -.
DR VEuPathDB; HostDB:ENSG00000132781; -.
DR eggNOG; KOG2457; Eukaryota.
DR GeneTree; ENSGT00510000047220; -.
DR HOGENOM; CLU_012862_0_0_1; -.
DR InParanoid; Q9UIF7; -.
DR OMA; THIRLKM; -.
DR OrthoDB; 616758at2759; -.
DR PhylomeDB; Q9UIF7; -.
DR TreeFam; TF328549; -.
DR PathwayCommons; Q9UIF7; -.
DR Reactome; R-HSA-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-HSA-110331; Cleavage of the damaged purine.
DR Reactome; R-HSA-110357; Displacement of DNA glycosylase by APEX1.
DR Reactome; R-HSA-9608287; Defective MUTYH substrate binding. [Q9UIF7-3]
DR Reactome; R-HSA-9608290; Defective MUTYH substrate processing.
DR SignaLink; Q9UIF7; -.
DR SIGNOR; Q9UIF7; -.
DR BioGRID-ORCS; 4595; 17 hits in 1080 CRISPR screens.
DR EvolutionaryTrace; Q9UIF7; -.
DR GeneWiki; MUTYH; -.
DR GenomeRNAi; 4595; -.
DR Pharos; Q9UIF7; Tbio.
DR PRO; PR:Q9UIF7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UIF7; protein.
DR Bgee; ENSG00000132781; Expressed in cerebellar hemisphere and 93 other tissues.
DR ExpressionAtlas; Q9UIF7; baseline and differential.
DR Genevisible; Q9UIF7; HS.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032407; F:MutSalpha complex binding; IDA:HGNC-UCL.
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; IMP:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0045007; P:depurination; TAS:Reactome.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0006298; P:mismatch repair; IBA:GO_Central.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IEA:Ensembl.
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; 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; Alternative splicing; Disease variant; DNA damage;
KW DNA repair; Glycosidase; Hydrolase; Iron; Iron-sulfur; Metal-binding;
KW Mitochondrion; Nucleus; Reference proteome; Tumor suppressor.
FT CHAIN 1..546
FT /note="Adenine DNA glycosylase"
FT /id="PRO_0000102239"
FT DOMAIN 364..495
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 19..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 404..426
FT /note="Nudix box"
FT ACT_SITE 131
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT BINDING 287
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 294
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 303
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT SITE 233
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform Beta-1, isoform Gamma-2 and
FT isoform Gamma-3)"
FT /evidence="ECO:0000303|PubMed:10684930"
FT /id="VSP_010548"
FT VAR_SEQ 53..63
FT /note="Missing (in isoform Alpha-3 and isoform Gamma-3)"
FT /evidence="ECO:0000303|PubMed:10684930,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010550"
FT VAR_SEQ 53..62
FT /note="Missing (in isoform Alpha-2 and isoform Gamma-2)"
FT /evidence="ECO:0000303|PubMed:10684930"
FT /id="VSP_010549"
FT VARIANT 18
FT /note="P -> L (in FAP2; also found in multiple polyposis,
FT colorectal and lung cancer cases; unknown pathological
FT significance; decreased function in DNA repair;
FT dbSNP:rs79777494)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077640"
FT VARIANT 22
FT /note="V -> M (does not affect function in DNA repair;
FT dbSNP:rs3219484)"
FT /evidence="ECO:0000269|PubMed:12606733,
FT ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:25820570,
FT ECO:0000269|Ref.4"
FT /id="VAR_018872"
FT VARIANT 25
FT /note="G -> D (does not affect function in DNA repair;
FT dbSNP:rs75321043)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077641"
FT VARIANT 72
FT /note="V -> E (likely benign variant; does not affect DNA
FT glycosylase activity)"
FT /evidence="ECO:0000269|PubMed:20848659"
FT /id="VAR_077642"
FT VARIANT 100
FT /note="W -> R (found in sporadic hepatocellular carcinoma;
FT unknown pathological significance; loss of function in DNA
FT repair; dbSNP:rs1140507)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077643"
FT VARIANT 102
FT /note="D -> N (found in multiple polyposis and sporadic
FT colorectal cancer cases; unknown pathological significance;
FT does not affect DNA glycosylase activity; does not affect
FT function in DNA repair; dbSNP:rs587780746)"
FT /evidence="ECO:0000269|PubMed:25820570,
FT ECO:0000269|PubMed:26694661"
FT /id="VAR_077644"
FT VARIANT 121
FT /note="D -> G (likely benign variant; does not affect DNA
FT glycosylase activity; does not affect function in DNA
FT repair)"
FT /evidence="ECO:0000269|PubMed:26694661"
FT /id="VAR_077645"
FT VARIANT 125
FT /note="Y -> H (in FAP2; decreased function in DNA repair)"
FT /evidence="ECO:0000269|PubMed:15366000,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026045"
FT VARIANT 128
FT /note="W -> R (in FAP2; loss of function in DNA repair;
FT dbSNP:rs730881832)"
FT /evidence="ECO:0000269|PubMed:12853198,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026046"
FT VARIANT 148
FT /note="G -> GIW (in FAP2; reduced DNA glycosylase activity;
FT decreased DNA binding; loss of function in DNA repair)"
FT /evidence="ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:19953527, ECO:0000269|PubMed:20418187"
FT /id="VAR_064938"
FT VARIANT 154
FT /note="P -> L (in FAP2; decreased function in DNA repair;
FT dbSNP:rs777184451)"
FT /evidence="ECO:0000269|PubMed:16557584,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_077646"
FT VARIANT 176
FT /note="Y -> C (in FAP2; loss of DNA glycosylase activity;
FT decreased DNA binding; loss of function in DNA repair;
FT dbSNP:rs34612342)"
FT /evidence="ECO:0000269|PubMed:11818965,
FT ECO:0000269|PubMed:12606733, ECO:0000269|PubMed:12853198,
FT ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:16941501,
FT ECO:0000269|PubMed:18091433, ECO:0000269|PubMed:19953527,
FT ECO:0000269|PubMed:20418187, ECO:0000269|PubMed:20848659,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_018873"
FT VARIANT 177
FT /note="Y -> S (in FAP2)"
FT /evidence="ECO:0000269|PubMed:16941501"
FT /id="VAR_077647"
FT VARIANT 179
FT /note="R -> C (in FAP2; also found in multiple polyposis
FT and colorectal cancer cases; loss of function in DNA
FT repair; dbSNP:rs747993448)"
FT /evidence="ECO:0000269|PubMed:18091433,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_064939"
FT VARIANT 179
FT /note="R -> H (in FAP2; loss of DNA glycosylase activity;
FT loss of function in DNA repair; dbSNP:rs143353451)"
FT /evidence="ECO:0000269|PubMed:15366000,
FT ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:20848659,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026047"
FT VARIANT 182
FT /note="R -> Q (in FAP2; loss of function in DNA repair;
FT dbSNP:rs533899702)"
FT /evidence="ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_077648"
FT VARIANT 182
FT /note="R -> W (in FAP2; loss of DNA glycosylase activity;
FT loss of DNA binding; loss of function in DNA repair;
FT dbSNP:rs750592289)"
FT /evidence="ECO:0000269|PubMed:18091433,
FT ECO:0000269|PubMed:19953527, ECO:0000269|PubMed:20418187"
FT /id="VAR_064940"
FT VARIANT 186
FT /note="G -> E (in FAP2; decreased function in DNA repair;
FT dbSNP:rs754155145)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077649"
FT VARIANT 213
FT /note="G -> E (in FAP2; dbSNP:rs768553551)"
FT /evidence="ECO:0000269|PubMed:18515411"
FT /id="VAR_077650"
FT VARIANT 220
FT /note="I -> V (in FAP2; also found in multiple polyposis
FT case; unknown pathological significance; reduced DNA
FT glycosylase activity; no effect on function in DNA repair;
FT dbSNP:rs200872702)"
FT /evidence="ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570"
FT /id="VAR_077651"
FT VARIANT 224
FT /note="A -> V (decreased function in DNA repair;
FT dbSNP:rs11545695)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077652"
FT VARIANT 231
FT /note="V -> M (probable disease-associated variant found in
FT a case of familial colorectal cancer; no significant effect
FT on DNA glycosylase activity; slightly decreased function in
FT DNA repair; dbSNP:rs200165598)"
FT /evidence="ECO:0000269|PubMed:25820570,
FT ECO:0000269|PubMed:26694661"
FT /id="VAR_077653"
FT VARIANT 235
FT /note="N -> S (in FAP2; loss of DNA glycosylase activity;
FT loss of function in DNA repair; dbSNP:rs1057517765)"
FT /evidence="ECO:0000269|PubMed:18515411,
FT ECO:0000269|PubMed:26694661"
FT /id="VAR_077654"
FT VARIANT 238
FT /note="R -> W (in FAP2; also found in a case of sporadic
FT colorectal cancer; unknown pathological significance;
FT decreased function in DNA repair; dbSNP:rs34126013)"
FT /evidence="ECO:0000269|PubMed:15366000,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026048"
FT VARIANT 242
FT /note="R -> C (probable disease-associated variant found in
FT multiple polyposis cases; decreased function in DNA repair;
FT dbSNP:rs200495564)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077655"
FT VARIANT 242
FT /note="R -> H (in FAP2; loss of function in DNA repair;
FT dbSNP:rs140342925)"
FT /evidence="ECO:0000269|PubMed:16134147,
FT ECO:0000269|PubMed:16287072, ECO:0000269|PubMed:16557584,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_077656"
FT VARIANT 243
FT /note="V -> F (does not affect function;
FT dbSNP:rs587780749)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077657"
FT VARIANT 244
FT /note="R -> G (reduced DNA glycosylase activity; decreased
FT function in DNA repair; dbSNP:rs587782885)"
FT /evidence="ECO:0000269|PubMed:26694661"
FT /id="VAR_077658"
FT VARIANT 271
FT /note="R -> W (in FAP2; loss of function in DNA repair;
FT dbSNP:rs769237459)"
FT /evidence="ECO:0000269|PubMed:16134147,
FT ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:25820570"
FT /id="VAR_077659"
FT VARIANT 280
FT /note="M -> V (in FAP2; reduced DNA glycosylase activity;
FT dbSNP:rs876659676)"
FT /evidence="ECO:0000269|PubMed:16941501,
FT ECO:0000269|PubMed:20848659"
FT /id="VAR_077660"
FT VARIANT 283
FT /note="G -> E (in FAP2; also found in a patient with
FT multiple polyps; unknown pathological significance; does
FT not affect function in DNA repair; dbSNP:rs730881833)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077661"
FT VARIANT 287
FT /note="C -> W (found in a case of sporadic lung cancer;
FT unknown pathological significance; loss of function in DNA
FT repair)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077662"
FT VARIANT 292
FT /note="P -> L (in FAP2; also found in multiple polyposis
FT cases; loss of function in DNA repair; dbSNP:rs374950566)"
FT /evidence="ECO:0000269|PubMed:16557584,
FT ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:25820570"
FT /id="VAR_077663"
FT VARIANT 306
FT /note="R -> C (in FAP2; also found in multiple polyposis
FT cases; unknown pathological significance; does not affect
FT DNA glycosylase activity; slightly decreased function in
FT DNA repair; dbSNP:rs138089183)"
FT /evidence="ECO:0000269|PubMed:16557584,
FT ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570"
FT /id="VAR_077664"
FT VARIANT 319
FT /note="S -> N (does not affect DNA glycosylase activity;
FT does not affect function in DNA repair; dbSNP:rs587781810)"
FT /evidence="ECO:0000269|PubMed:26694661"
FT /id="VAR_077665"
FT VARIANT 335
FT /note="Q -> H (does not affect function in DNA repair;
FT dbSNP:rs3219489)"
FT /evidence="ECO:0000269|PubMed:12606733,
FT ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:25820570,
FT ECO:0000269|Ref.4"
FT /id="VAR_018874"
FT VARIANT 335
FT /note="Q -> R (found in a family with non-polyposis
FT colorectal cancer-like syndrome; unknown pathological
FT significance; does not affect function in DNA repair;
FT dbSNP:rs199742231)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077666"
FT VARIANT 370
FT /note="A -> V (does not affect DNA glycosylase activity;
FT dbSNP:rs35352891)"
FT /evidence="ECO:0000269|PubMed:20848659"
FT /id="VAR_048262"
FT VARIANT 377
FT /note="P -> T (in FAP2; decreased function in DNA repair)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077667"
FT VARIANT 385
FT /note="L -> P (in FAP2; also found in multiple polyposis
FT cases; loss of DNA glycosylase activity; loss of function
FT in DNA repair; dbSNP:rs1060501335)"
FT /evidence="ECO:0000269|PubMed:16134147,
FT ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:20848659,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_077668"
FT VARIANT 393
FT /note="G -> D (in FAP2; reduced DNA glycosylase activity;
FT decreased DNA binding; decreased function in DNA repair;
FT dbSNP:rs36053993)"
FT /evidence="ECO:0000269|PubMed:11818965,
FT ECO:0000269|PubMed:12606733, ECO:0000269|PubMed:12853198,
FT ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072,
FT ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:16941501,
FT ECO:0000269|PubMed:18091433, ECO:0000269|PubMed:19953527,
FT ECO:0000269|PubMed:20418187, ECO:0000269|PubMed:20848659,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_018875"
FT VARIANT 402
FT /note="P -> L (in FAP2; also found in multiple polyposis
FT and colorectal cancer cases; loss of DNA glycosylase
FT activity; loss of function in DNA repair;
FT dbSNP:rs529008617)"
FT /evidence="ECO:0000269|PubMed:16557584,
FT ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570"
FT /id="VAR_077669"
FT VARIANT 402
FT /note="P -> S (in GASC; sporadic; decreased function in DNA
FT repair; dbSNP:rs121908382)"
FT /evidence="ECO:0000269|PubMed:15273732,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026049"
FT VARIANT 411
FT /note="Q -> R (in GASC; sporadic; unknown pathological
FT significance; does not affect function in DNA repair;
FT dbSNP:rs121908383)"
FT /evidence="ECO:0000269|PubMed:15273732,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026050"
FT VARIANT 417
FT /note="L -> M (in FAP2; also found in patient with multiple
FT polyps and in a family with non-polyposis colorectal
FT cancer-like syndrome; unknown pathological significance;
FT does not affect function in DNA repair; dbSNP:rs144079536)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077670"
FT VARIANT 423
FT /note="R -> C (in FAP2; unknown pathological significance;
FT does not affect function in DNA repair; dbSNP:rs150792276)"
FT /evidence="ECO:0000269|PubMed:16134147,
FT ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:25820570"
FT /id="VAR_077671"
FT VARIANT 434
FT /note="R -> P (found in sporadic colorectal cancer cases;
FT unknown pathological significance; decreased function in
FT DNA repair)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077672"
FT VARIANT 434
FT /note="R -> Q (does not affect function in DNA repair;
FT dbSNP:rs587782120)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077673"
FT VARIANT 470
FT /note="A -> D (in FAP2; loss of function in DNA repair;
FT dbSNP:rs200844166)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077674"
FT VARIANT 470
FT /note="A -> T (found in patient with multiple polyposis;
FT unknown pathological significance; does not affect function
FT in DNA repair; dbSNP:rs192816572)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077675"
FT VARIANT 474
FT /note="T -> M (in FAP2; unknown pathological significance;
FT dbSNP:rs767747402)"
FT /evidence="ECO:0000269|PubMed:18515411"
FT /id="VAR_077676"
FT VARIANT 477
FT /note="Missing (in FAP2; also found in a case of sporadic
FT colorectal cancer; loss of DNA glycosylase activity; loss
FT of DNA binding; loss of function in DNA repair)"
FT /evidence="ECO:0000269|PubMed:16134147,
FT ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:19953527,
FT ECO:0000269|PubMed:20418187, ECO:0000269|PubMed:20848659,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_064941"
FT VARIANT 486
FT /note="A -> T (in FAP2; decreased function in DNA repair;
FT dbSNP:rs587782263)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077677"
FT VARIANT 490
FT /note="V -> F (in FAP2; found also in sporadic colorectal
FT cancer cases; unknown pathological significance; decreased
FT function in DNA repair; dbSNP:rs587782228)"
FT /evidence="ECO:0000269|PubMed:16557584,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_077678"
FT VARIANT 500
FT /note="G -> E (decreased function in DNA repair;
FT dbSNP:rs3219494)"
FT /evidence="ECO:0000269|PubMed:25820570, ECO:0000269|Ref.4"
FT /id="VAR_018876"
FT VARIANT 512
FT /note="S -> F (does not affect DNA glycosylase activity;
FT does not affect function in DNA repair; dbSNP:rs140118273)"
FT /evidence="ECO:0000269|PubMed:12606733,
FT ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:20848659,
FT ECO:0000269|PubMed:25820570"
FT /id="VAR_026051"
FT VARIANT 513
FT /note="P -> L (does not affect function in DNA repair;
FT dbSNP:rs587778542)"
FT /evidence="ECO:0000269|PubMed:25820570"
FT /id="VAR_077679"
FT VARIANT 520
FT /note="R -> H (does not affect DNA glycosylase activity;
FT does not affect function in DNA repair; dbSNP:rs374655042)"
FT /evidence="ECO:0000269|PubMed:26694661"
FT /id="VAR_077680"
FT VARIANT 526
FT /note="L -> M (does not affect function in DNA repair;
FT dbSNP:rs3219496)"
FT /evidence="ECO:0000269|PubMed:25820570, ECO:0000269|Ref.4"
FT /id="VAR_018877"
FT VARIANT 531
FT /note="R -> Q (does not affect function in DNA repair;
FT dbSNP:rs3219497)"
FT /evidence="ECO:0000269|PubMed:25820570, ECO:0000269|Ref.4"
FT /id="VAR_018878"
FT VARIANT 536
FT /note="T -> A (does not affect DNA glycosylase activity;
FT does not affect function in DNA repair; dbSNP:rs151196169)"
FT /evidence="ECO:0000269|PubMed:26694661"
FT /id="VAR_077681"
FT MUTAGEN 233
FT /note="D->N: Loss of DNA glycosylase activity."
FT /evidence="ECO:0000269|PubMed:20848659"
FT HELIX 87..104
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 109..116
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 120..135
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 139..152
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 156..160
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 164..171
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 177..193
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 202..208
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 234..243
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 253..266
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 272..285
FT /evidence="ECO:0007829|PDB:3N5N"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 304..316
FT /evidence="ECO:0007829|PDB:3N5N"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:3N5N"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:1X51"
FT STRAND 366..377
FT /evidence="ECO:0007829|PDB:1X51"
FT STRAND 379..388
FT /evidence="ECO:0007829|PDB:1X51"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:1X51"
FT HELIX 410..424
FT /evidence="ECO:0007829|PDB:1X51"
FT STRAND 447..456
FT /evidence="ECO:0007829|PDB:1X51"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:1X51"
FT HELIX 475..480
FT /evidence="ECO:0007829|PDB:1X51"
FT HELIX 485..495
FT /evidence="ECO:0007829|PDB:1X51"
SQ SEQUENCE 546 AA; 60069 MW; 6C79BDB34345DD10 CRC64;
MTPLVSRLSR LWAIMRKPRA AVGSGHRKQA ASQEGRQKHA KNNSQAKPSA CDGMIAECPG
APAGLARQPE EVVLQASVSS YHLFRDVAEV TAFRGSLLSW YDQEKRDLPW RRRAEDEMDL
DRRAYAVWVS EVMLQQTQVA TVINYYTGWM QKWPTLQDLA SASLEEVNQL WAGLGYYSRG
RRLQEGARKV VEELGGHMPR TAETLQQLLP GVGRYTAGAI ASIAFGQATG VVDGNVARVL
CRVRAIGADP SSTLVSQQLW GLAQQLVDPA RPGDFNQAAM ELGATVCTPQ RPLCSQCPVE
SLCRARQRVE QEQLLASGSL SGSPDVEECA PNTGQCHLCL PPSEPWDQTL GVVNFPRKAS
RKPPREESSA TCVLEQPGAL GAQILLVQRP NSGLLAGLWE FPSVTWEPSE QLQRKALLQE
LQRWAGPLPA THLRHLGEVV HTFSHIKLTY QVYGLALEGQ TPVTTVPPGA RWLTQEEFHT
AAVSTAMKKV FRVYQGQQPG TCMGSKRSQV SSPCSRKKPR MGQQVLDNFF RSHISTDAHS
LNSAAQ
