TDG_HUMAN
ID TDG_HUMAN Reviewed; 410 AA.
AC Q13569; Q8IUZ6; Q8IZM3;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=G/T mismatch-specific thymine DNA glycosylase;
DE EC=3.2.2.29;
DE AltName: Full=Thymine-DNA glycosylase;
DE Short=hTDG;
GN Name=TDG;
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 [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=8662714; DOI=10.1074/jbc.271.22.12767;
RA Neddermann P., Gallinari P., Lettieri T., Schmid D., Truong O., Hsuan J.J.,
RA Wiebauer K., Jiricny J.;
RT "Cloning and expression of human G/T mismatch-specific thymine-DNA
RT glycosylase.";
RL J. Biol. Chem. 271:12767-12774(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-199 AND MET-367.
RG NIEHS SNPs program;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP FUNCTION.
RX PubMed=8127859; DOI=10.1073/pnas.91.5.1642;
RA Neddermann P., Jiricny J.;
RT "Efficient removal of uracil from G.U mispairs by the mismatch-specific
RT thymine DNA glycosylase from HeLa cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:1642-1646(1994).
RN [6]
RP FUNCTION.
RX PubMed=8407958; DOI=10.1016/s0021-9258(19)36913-3;
RA Neddermann P., Jiricny J.;
RT "The purification of a mismatch-specific thymine-DNA glycosylase from HeLa
RT cells.";
RL J. Biol. Chem. 268:21218-21224(1993).
RN [7]
RP SUMOYLATION AT LYS-330.
RX PubMed=11889051; DOI=10.1093/emboj/21.6.1456;
RA Hardeland U., Steinacher R., Jiricny J., Schaer P.;
RT "Modification of the human thymine-DNA glycosylase by ubiquitin-like
RT proteins facilitates enzymatic turnover.";
RL EMBO J. 21:1456-1464(2002).
RN [8]
RP INTERACTION WITH AICDA AND GADD45A.
RX PubMed=21722948; DOI=10.1016/j.cell.2011.06.020;
RA Cortellino S., Xu J., Sannai M., Moore R., Caretti E., Cigliano A.,
RA Le Coz M., Devarajan K., Wessels A., Soprano D., Abramowitz L.K.,
RA Bartolomei M.S., Rambow F., Bassi M.R., Bruno T., Fanciulli M., Renner C.,
RA Klein-Szanto A.J., Matsumoto Y., Kobi D., Davidson I., Alberti C.,
RA Larue L., Bellacosa A.;
RT "Thymine DNA glycosylase is essential for active DNA demethylation by
RT linked deamination-base excision repair.";
RL Cell 146:67-79(2011).
RN [9]
RP FUNCTION.
RX PubMed=21862836; DOI=10.1074/jbc.c111.284620;
RA Maiti A., Drohat A.C.;
RT "Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-
RT carboxylcytosine: potential implications for active demethylation of CpG
RT sites.";
RL J. Biol. Chem. 286:35334-35338(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-330, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [12]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-330, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-330, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-103; LYS-248 AND LYS-330, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 112-339 CONJUGATED TO SUMO1, AND
RP MUTAGENESIS OF ARG-281; GLU-310 AND PHE-315.
RX PubMed=15959518; DOI=10.1038/nature03634;
RA Baba D., Maita N., Jee J.-G., Uchimura Y., Saitoh H., Sugasawa K.,
RA Hanaoka F., Tochio H., Hiroaki H., Shirakawa M.;
RT "Crystal structure of thymine DNA glycosylase conjugated to SUMO-1.";
RL Nature 435:979-982(2005).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 112-339 CONJUGATED TO SUMO2, AND
RP MUTAGENESIS OF GLU-310.
RX PubMed=16626738; DOI=10.1016/j.jmb.2006.03.036;
RA Baba D., Maita N., Jee J.-G., Uchimura Y., Saitoh H., Sugasawa K.,
RA Hanaoka F., Tochio H., Hiroaki H., Shirakawa M.;
RT "Crystal structure of SUMO-3-modified thymine-DNA glycosylase.";
RL J. Mol. Biol. 359:137-147(2006).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 111-308 IN COMPLEX WITH DNA, AND
RP SUBUNIT.
RX PubMed=18587051; DOI=10.1073/pnas.0711061105;
RA Maiti A., Morgan M.T., Pozharski E., Drohat A.C.;
RT "Crystal structure of human thymine DNA glycosylase bound to DNA elucidates
RT sequence-specific mismatch recognition.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:8890-8895(2008).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 111-308 IN COMPLEX WITH DNA,
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF ASN-140.
RX PubMed=22327402; DOI=10.1038/nchembio.914;
RA Zhang L., Lu X., Lu J., Liang H., Dai Q., Xu G.L., Luo C., Jiang H., He C.;
RT "Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-
RT modified DNA.";
RL Nat. Chem. Biol. 8:328-330(2012).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 111-308 IN COMPLEX WITH DNA, AND
RP FUNCTION.
RX PubMed=22962365; DOI=10.1093/nar/gks845;
RA Hashimoto H., Hong S., Bhagwat A.S., Zhang X., Cheng X.;
RT "Excision of 5-hydroxymethyluracil and 5-carboxylcytosine by the thymine
RT DNA glycosylase domain: its structural basis and implications for active
RT DNA demethylation.";
RL Nucleic Acids Res. 40:10203-10214(2012).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.97 ANGSTROMS) OF 111-308 IN COMPLEX WITH DNA,
RP FUNCTION, AND MUTAGENESIS OF ALA-145; HIS-151; ASN-191 AND THR-197.
RX PubMed=22573813; DOI=10.1073/pnas.1201010109;
RA Maiti A., Noon M.S., MacKerell A.D. Jr., Pozharski E., Drohat A.C.;
RT "Lesion processing by a repair enzyme is severely curtailed by residues
RT needed to prevent aberrant activity on undamaged DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:8091-8096(2012).
CC -!- FUNCTION: DNA glycosylase that plays a key role in active DNA
CC demethylation: specifically recognizes and binds 5-formylcytosine (5fC)
CC and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates
CC their excision through base-excision repair (BER) to install an
CC unmethylated cytosine. Cannot remove 5-hydroxymethylcytosine (5hmC).
CC According to an alternative model, involved in DNA demethylation by
CC mediating DNA glycolase activity toward 5-hydroxymethyluracil (5hmU)
CC produced by deamination of 5hmC. Also involved in DNA repair by acting
CC as a thymine-DNA glycosylase that mediates correction of G/T mispairs
CC to G/C pairs: in the DNA of higher eukaryotes, hydrolytic deamination
CC of 5-methylcytosine to thymine leads to the formation of G/T
CC mismatches. Its role in the repair of canonical base damage is however
CC minor compared to its role in DNA demethylation. It is capable of
CC hydrolyzing the carbon-nitrogen bond between the sugar-phosphate
CC backbone of the DNA and a mispaired thymine. In addition to the G/T, it
CC can remove thymine also from C/T and T/T mispairs in the order G/T >>
CC C/T > T/T. It has no detectable activity on apyrimidinic sites and does
CC not catalyze the removal of thymine from A/T pairs or from single-
CC stranded DNA. It can also remove uracil and 5-bromouracil from mispairs
CC with guanine. {ECO:0000269|PubMed:21862836,
CC ECO:0000269|PubMed:22327402, ECO:0000269|PubMed:22573813,
CC ECO:0000269|PubMed:22962365, ECO:0000269|PubMed:8127859,
CC ECO:0000269|PubMed:8407958, ECO:0000269|PubMed:8662714}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes mismatched double-stranded DNA and polynucleotides,
CC releasing free thymine.; EC=3.2.2.29;
CC -!- SUBUNIT: Homodimer. Interacts with AICDA and GADD45A.
CC {ECO:0000269|PubMed:18587051, ECO:0000269|PubMed:21722948,
CC ECO:0000269|PubMed:22327402, ECO:0000269|PubMed:22573813,
CC ECO:0000269|PubMed:22962365}.
CC -!- INTERACTION:
CC Q13569; Q9GZX7: AICDA; NbExp=5; IntAct=EBI-348333, EBI-3834328;
CC Q13569; Q92870-2: APBB2; NbExp=3; IntAct=EBI-348333, EBI-21535880;
CC Q13569; P24522: GADD45A; NbExp=3; IntAct=EBI-348333, EBI-448167;
CC Q13569; P28799: GRN; NbExp=3; IntAct=EBI-348333, EBI-747754;
CC Q13569; P04792: HSPB1; NbExp=3; IntAct=EBI-348333, EBI-352682;
CC Q13569; O60333-2: KIF1B; NbExp=3; IntAct=EBI-348333, EBI-10975473;
CC Q13569; Q15788: NCOA1; NbExp=8; IntAct=EBI-348333, EBI-455189;
CC Q13569; Q15788-2: NCOA1; NbExp=2; IntAct=EBI-348333, EBI-5327712;
CC Q13569; P07196: NEFL; NbExp=3; IntAct=EBI-348333, EBI-475646;
CC Q13569; D3DTS7: PMP22; NbExp=3; IntAct=EBI-348333, EBI-25882629;
CC Q13569; P60891: PRPS1; NbExp=3; IntAct=EBI-348333, EBI-749195;
CC Q13569; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-348333, EBI-396669;
CC Q13569; P37840: SNCA; NbExp=3; IntAct=EBI-348333, EBI-985879;
CC Q13569; P63165: SUMO1; NbExp=3; IntAct=EBI-348333, EBI-80140;
CC Q13569; P61956: SUMO2; NbExp=2; IntAct=EBI-348333, EBI-473220;
CC Q13569; P02766: TTR; NbExp=3; IntAct=EBI-348333, EBI-711909;
CC Q13569; O76024: WFS1; NbExp=3; IntAct=EBI-348333, EBI-720609;
CC Q13569; O88846: Rnf4; Xeno; NbExp=2; IntAct=EBI-348333, EBI-7258907;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8662714}.
CC -!- PTM: Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces
CC dissociation of the product DNA. {ECO:0000269|PubMed:11889051}.
CC -!- SIMILARITY: Belongs to the uracil-DNA glycosylase (UDG) superfamily.
CC TDG/mug family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tdg/";
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DR EMBL; U51166; AAC50540.1; -; mRNA.
DR EMBL; AF545435; AAN16399.1; -; Genomic_DNA.
DR EMBL; AC078819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037557; AAH37557.1; -; mRNA.
DR CCDS; CCDS9095.1; -.
DR RefSeq; NP_003202.3; NM_003211.4.
DR PDB; 1WYW; X-ray; 2.10 A; A=112-339.
DR PDB; 2D07; X-ray; 2.10 A; A=112-339.
DR PDB; 2RBA; X-ray; 2.79 A; A/B=111-308.
DR PDB; 3UFJ; X-ray; 2.97 A; A/B=111-308.
DR PDB; 3UO7; X-ray; 3.00 A; A/B=111-308.
DR PDB; 3UOB; X-ray; 3.01 A; A/B=111-308.
DR PDB; 4FNC; X-ray; 2.49 A; A=111-308.
DR PDB; 4JGC; X-ray; 2.58 A; A=111-308.
DR PDB; 4XEG; X-ray; 1.72 A; A=111-308.
DR PDB; 4Z3A; X-ray; 1.72 A; A=111-308.
DR PDB; 4Z47; X-ray; 1.45 A; A=111-308.
DR PDB; 4Z7B; X-ray; 2.02 A; A=111-308.
DR PDB; 4Z7Z; X-ray; 1.83 A; A=111-308.
DR PDB; 5CYS; X-ray; 2.45 A; A=111-308.
DR PDB; 5FF8; X-ray; 1.70 A; A=82-308.
DR PDB; 5HF7; X-ray; 1.54 A; A=82-308.
DR PDB; 5JXY; X-ray; 1.71 A; A=111-308.
DR PDB; 5T2W; X-ray; 2.20 A; A=82-308.
DR PDB; 6U15; X-ray; 2.40 A; A=82-308.
DR PDB; 6U16; X-ray; 1.60 A; A=82-308.
DR PDB; 6U17; X-ray; 1.55 A; A=82-308.
DR PDBsum; 1WYW; -.
DR PDBsum; 2D07; -.
DR PDBsum; 2RBA; -.
DR PDBsum; 3UFJ; -.
DR PDBsum; 3UO7; -.
DR PDBsum; 3UOB; -.
DR PDBsum; 4FNC; -.
DR PDBsum; 4JGC; -.
DR PDBsum; 4XEG; -.
DR PDBsum; 4Z3A; -.
DR PDBsum; 4Z47; -.
DR PDBsum; 4Z7B; -.
DR PDBsum; 4Z7Z; -.
DR PDBsum; 5CYS; -.
DR PDBsum; 5FF8; -.
DR PDBsum; 5HF7; -.
DR PDBsum; 5JXY; -.
DR PDBsum; 5T2W; -.
DR PDBsum; 6U15; -.
DR PDBsum; 6U16; -.
DR PDBsum; 6U17; -.
DR AlphaFoldDB; Q13569; -.
DR SMR; Q13569; -.
DR BioGRID; 112855; 51.
DR DIP; DIP-32709N; -.
DR ELM; Q13569; -.
DR IntAct; Q13569; 29.
DR MINT; Q13569; -.
DR STRING; 9606.ENSP00000376611; -.
DR iPTMnet; Q13569; -.
DR PhosphoSitePlus; Q13569; -.
DR BioMuta; TDG; -.
DR DMDM; 46397791; -.
DR EPD; Q13569; -.
DR MassIVE; Q13569; -.
DR MaxQB; Q13569; -.
DR PaxDb; Q13569; -.
DR PeptideAtlas; Q13569; -.
DR PRIDE; Q13569; -.
DR ProteomicsDB; 59573; -.
DR Antibodypedia; 30563; 418 antibodies from 31 providers.
DR DNASU; 6996; -.
DR Ensembl; ENST00000392872.8; ENSP00000376611.3; ENSG00000139372.15.
DR GeneID; 6996; -.
DR KEGG; hsa:6996; -.
DR MANE-Select; ENST00000392872.8; ENSP00000376611.3; NM_003211.6; NP_003202.3.
DR UCSC; uc001tkg.4; human.
DR CTD; 6996; -.
DR DisGeNET; 6996; -.
DR GeneCards; TDG; -.
DR HGNC; HGNC:11700; TDG.
DR HPA; ENSG00000139372; Low tissue specificity.
DR MIM; 601423; gene.
DR neXtProt; NX_Q13569; -.
DR OpenTargets; ENSG00000139372; -.
DR PharmGKB; PA36419; -.
DR VEuPathDB; HostDB:ENSG00000139372; -.
DR eggNOG; KOG4120; Eukaryota.
DR GeneTree; ENSGT00390000000987; -.
DR HOGENOM; CLU_045775_1_0_1; -.
DR InParanoid; Q13569; -.
DR OMA; YCEGSSF; -.
DR OrthoDB; 1209629at2759; -.
DR PhylomeDB; Q13569; -.
DR TreeFam; TF328764; -.
DR BRENDA; 3.2.2.29; 2681.
DR PathwayCommons; Q13569; -.
DR Reactome; R-HSA-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
DR Reactome; R-HSA-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-HSA-110357; Displacement of DNA glycosylase by APEX1.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-5221030; TET1,2,3 and TDG demethylate DNA.
DR SignaLink; Q13569; -.
DR BioGRID-ORCS; 6996; 43 hits in 1042 CRISPR screens.
DR ChiTaRS; TDG; human.
DR EvolutionaryTrace; Q13569; -.
DR GeneWiki; Thymine-DNA_glycosylase; -.
DR GenomeRNAi; 6996; -.
DR Pharos; Q13569; Tbio.
DR PRO; PR:Q13569; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q13569; protein.
DR Bgee; ENSG00000139372; Expressed in buccal mucosa cell and 207 other tissues.
DR ExpressionAtlas; Q13569; baseline and differential.
DR Genevisible; Q13569; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0016605; C:PML body; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:CAFA.
DR GO; GO:0031404; F:chloride ion binding; IDA:CAFA.
DR GO; GO:0003684; F:damaged DNA binding; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0019104; F:DNA N-glycosylase activity; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0043739; F:G/U mismatch-specific uracil-DNA glycosylase activity; IMP:CAFA.
DR GO; GO:0000287; F:magnesium ion binding; IDA:CAFA.
DR GO; GO:0030983; F:mismatched DNA binding; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl.
DR GO; GO:0043621; F:protein self-association; IDA:CAFA.
DR GO; GO:0008263; F:pyrimidine-specific mismatch base pair DNA N-glycosylase activity; IDA:UniProtKB.
DR GO; GO:0031402; F:sodium ion binding; IDA:CAFA.
DR GO; GO:0032183; F:SUMO binding; IPI:CAFA.
DR GO; GO:0003712; F:transcription coregulator activity; IEA:Ensembl.
DR GO; GO:0004844; F:uracil DNA N-glycosylase activity; IDA:CAFA.
DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB.
DR GO; GO:0006285; P:base-excision repair, AP site formation; IDA:CAFA.
DR GO; GO:0045008; P:depyrimidination; TAS:Reactome.
DR GO; GO:0080111; P:DNA demethylation; ISS:UniProtKB.
DR GO; GO:0006298; P:mismatch repair; IDA:UniProtKB.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0035511; P:oxidative DNA demethylation; TAS:Reactome.
DR GO; GO:1902544; P:regulation of DNA N-glycosylase activity; IMP:CAFA.
DR GO; GO:0045995; P:regulation of embryonic development; ISS:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISS:UniProtKB.
DR CDD; cd10028; UDG-F2_TDG_MUG; 1.
DR DisProt; DP00719; -.
DR Gene3D; 3.40.470.10; -; 1.
DR InterPro; IPR015637; MUG/TDG.
DR InterPro; IPR003310; TDG-like_euk.
DR InterPro; IPR005122; Uracil-DNA_glycosylase-like.
DR InterPro; IPR036895; Uracil-DNA_glycosylase-like_sf.
DR PANTHER; PTHR12159; PTHR12159; 1.
DR Pfam; PF03167; UDG; 1.
DR SUPFAM; SSF52141; SSF52141; 1.
DR TIGRFAMs; TIGR00584; mug; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Chromatin regulator; Direct protein sequencing;
KW DNA damage; DNA repair; Hydrolase; Isopeptide bond; Nucleus;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..410
FT /note="G/T mismatch-specific thymine DNA glycosylase"
FT /id="PRO_0000185777"
FT REGION 37..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 103
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 248
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 330
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 330
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT VARIANT 199
FT /note="G -> S (in dbSNP:rs4135113)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_018892"
FT VARIANT 367
FT /note="V -> L (in dbSNP:rs2888805)"
FT /id="VAR_059450"
FT VARIANT 367
FT /note="V -> M (in dbSNP:rs2888805)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_018893"
FT VARIANT 381
FT /note="G -> E (in dbSNP:rs3953597)"
FT /id="VAR_050140"
FT MUTAGEN 140
FT /note="N->A: Loss of DNA glycosylase activity but still
FT able to bind DNA."
FT /evidence="ECO:0000269|PubMed:22327402"
FT MUTAGEN 145
FT /note="A->G: Increased DNA glycosylase activity on G/T
FT mispairs."
FT /evidence="ECO:0000269|PubMed:22573813"
FT MUTAGEN 151
FT /note="H->A,Q: Increased DNA glycosylase activity on G/T
FT mispairs."
FT /evidence="ECO:0000269|PubMed:22573813"
FT MUTAGEN 191
FT /note="N->A: Reduced DNA glycosylase activity on G/T and
FT G/U mispairs."
FT /evidence="ECO:0000269|PubMed:22573813"
FT MUTAGEN 197
FT /note="T->A: Reduced DNA glycosylase activity on G/T
FT mispairs."
FT /evidence="ECO:0000269|PubMed:22573813"
FT MUTAGEN 281
FT /note="R->A: Restores the DNA-binding ability of the
FT sumoylated form."
FT /evidence="ECO:0000269|PubMed:15959518"
FT MUTAGEN 310
FT /note="E->Q: Restores the DNA-binding ability of the
FT sumoylated form."
FT /evidence="ECO:0000269|PubMed:15959518,
FT ECO:0000269|PubMed:16626738"
FT MUTAGEN 315
FT /note="F->A: Restores the DNA-binding ability of the
FT sumoylated form."
FT /evidence="ECO:0000269|PubMed:15959518"
FT CONFLICT 91
FT /note="S -> P (in Ref. 1; AAC50540)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="V -> G (in Ref. 4; AAH37557)"
FT /evidence="ECO:0000305"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:5CYS"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:4Z47"
FT HELIX 143..148
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:5HF7"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:4Z47"
FT HELIX 175..180
FT /evidence="ECO:0007829|PDB:4Z47"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:4Z47"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:4Z47"
FT HELIX 205..222
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:4Z47"
FT HELIX 232..243
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 265..269
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:2RBA"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2D07"
FT HELIX 282..304
FT /evidence="ECO:0007829|PDB:4Z47"
FT STRAND 308..314
FT /evidence="ECO:0007829|PDB:1WYW"
FT HELIX 317..329
FT /evidence="ECO:0007829|PDB:1WYW"
SQ SEQUENCE 410 AA; 46053 MW; 33752B26EBC789AE CRC64;
MEAENAGSYS LQQAQAFYTF PFQQLMAEAP NMAVVNEQQM PEEVPAPAPA QEPVQEAPKG
RKRKPRTTEP KQPVEPKKPV ESKKSGKSAK SKEKQEKITD TFKVKRKVDR FNGVSEAELL
TKTLPDILTF NLDIVIIGIN PGLMAAYKGH HYPGPGNHFW KCLFMSGLSE VQLNHMDDHT
LPGKYGIGFT NMVERTTPGS KDLSSKEFRE GGRILVQKLQ KYQPRIAVFN GKCIYEIFSK
EVFGVKVKNL EFGLQPHKIP DTETLCYVMP SSSARCAQFP RAQDKVHYYI KLKDLRDQLK
GIERNMDVQE VQYTFDLQLA QEDAKKMAVK EEKYDPGYEA AYGGAYGENP CSSEPCGFSS
NGLIESVELR GESAFSGIPN GQWMTQSFTD QIPSFSNHCG TQEQEEESHA
