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 27-MAR-2024, entry version 198. 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/"; 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; 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; 65. 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; 9606-ENSP00000376611; -. DR PeptideAtlas; Q13569; -. DR ProteomicsDB; 59573; -. DR Pumba; Q13569; -. DR Antibodypedia; 30563; 451 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 AGR; HGNC:11700; -. 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; ANMVNPE; -. DR OrthoDB; 5318912at2759; -. 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 SIGNOR; Q13569; -. DR BioGRID-ORCS; 6996; 61 hits in 1118 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 209 other cell types or tissues. DR ExpressionAtlas; Q13569; baseline and differential. 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:0141016; F:G/T mismatch-specific thymine-DNA glycosylase activity; IEA:UniProtKB-EC. 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:0003676; F:nucleic acid binding; EXP:DisProt. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. 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; IBA:GO_Central. DR GO; GO:0045008; P:depyrimidination; TAS:Reactome. DR GO; GO:0080111; P:DNA demethylation; TAS:Reactome. DR GO; GO:0040029; P:epigenetic regulation of gene expression; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0045995; P:regulation of embryonic development; IEA:Ensembl. DR CDD; cd10028; UDG-F2_TDG_MUG; 1. DR DisProt; DP00719; -. DR Gene3D; 3.40.470.10; Uracil-DNA glycosylase-like domain; 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 NCBIfam; TIGR00584; mug; 1. DR PANTHER; PTHR12159; G/T AND G/U MISMATCH-SPECIFIC DNA GLYCOSYLASE; 1. DR PANTHER; PTHR12159:SF9; G_T MISMATCH-SPECIFIC THYMINE DNA GLYCOSYLASE; 1. DR Pfam; PF03167; UDG; 1. DR SUPFAM; SSF52141; Uracil-DNA glycosylase-like; 1. DR Genevisible; Q13569; HS. 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 //