TDG_MOUSE
ID TDG_MOUSE Reviewed; 421 AA.
AC P56581; Q3TPW4; Q542A9; Q5U3M4; Q5U3M5; Q6PJW4; Q8BPK0;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=G/T mismatch-specific thymine DNA glycosylase;
DE EC=3.2.2.29;
DE AltName: Full=C-JUN leucine zipper interactive protein JZA-3;
DE AltName: Full=Thymine-DNA glycosylase;
GN Name=Tdg;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=9694815; DOI=10.1074/jbc.273.33.20728;
RA Um S., Harbers M., Benecke A., Pierrat B., Losson R., Chambon P.;
RT "Retinoic acid receptors interact physically and functionally with the T:G
RT mismatch-specific thymine-DNA glycosylase.";
RL J. Biol. Chem. 273:20728-20736(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Eye, Spinal cord, Stomach, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 249-397.
RC STRAIN=CD-1; TISSUE=Embryo;
RX PubMed=1631061; DOI=10.1073/pnas.89.13.5789;
RA Chevray P.M., Nathans D.;
RT "Protein interaction cloning in yeast: identification of mammalian proteins
RT that react with the leucine zipper of Jun.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5789-5793(1992).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASN-151.
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 [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASN-151.
RX PubMed=21278727; DOI=10.1038/nature09672;
RA Cortazar D., Kunz C., Selfridge J., Lettieri T., Saito Y., MacDougall E.,
RA Wirz A., Schuermann D., Jacobs A.L., Siegrist F., Steinacher R.,
RA Jiricny J., Bird A., Schar P.;
RT "Embryonic lethal phenotype reveals a function of TDG in maintaining
RT epigenetic stability.";
RL Nature 470:419-423(2011).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF ASN-151.
RX PubMed=21817016; DOI=10.1126/science.1210944;
RA He Y.F., Li B.Z., Li Z., Liu P., Wang Y., Tang Q., Ding J., Jia Y.,
RA Chen Z., Li L., Sun Y., Li X., Dai Q., Song C.X., Zhang K., He C., Xu G.L.;
RT "Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in
RT mammalian DNA.";
RL Science 333:1303-1307(2011).
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 (PubMed:21817016). Cannot remove 5-
CC hydroxymethylcytosine (5hmC). According to an alternative model,
CC involved in DNA demethylation by mediating DNA glycolase activity
CC toward 5-hydroxymethyluracil (5hmU) produced by deamination of 5hmC
CC (PubMed:21722948). Also involved in DNA repair by acting as a thymine-
CC DNA glycosylase that mediates correction of G/T mispairs to G/C pairs:
CC in the DNA of higher eukaryotes, hydrolytic deamination of 5-
CC methylcytosine to thymine leads to the formation of G/T mismatches. Its
CC role in the repair of canonical base damage is however minor compared
CC to its role in DNA demethylation. It is capable of hydrolyzing the
CC carbon-nitrogen bond between the sugar-phosphate backbone of the DNA
CC and a mispaired thymine. In addition to the G/T, it can remove thymine
CC also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no
CC detectable activity on apyrimidinic sites and does not catalyze the
CC removal of thymine from A/T pairs or from single-stranded DNA. It can
CC also remove uracil and 5-bromouracil from mispairs with guanine.
CC {ECO:0000269|PubMed:21278727, ECO:0000269|PubMed:21722948,
CC ECO:0000269|PubMed:21817016}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P56581; Q15788: NCOA1; Xeno; NbExp=4; IntAct=EBI-4320525, EBI-455189;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56581-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56581-2; Sequence=VSP_046491;
CC -!- PTM: Sumoylation on Lys-341 by either SUMO1 or SUMO2 induces
CC dissociation of the product DNA. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality between 10.5 and 12.5 dpc.
CC Embryos display specific patterning defects of the developing heart;
CC vasculogenesis defects of dorsal aortae, carotid arteries and branchial
CC arteries. Global defects of angiogenesis are also observed. Defects are
CC due to epigenetic aberrations affecting the expression of developmental
CC genes, coincident with imbalanced histone modification and CpG
CC methylation at promoters of affected genes.
CC {ECO:0000269|PubMed:21278727, ECO:0000269|PubMed:21722948}.
CC -!- SIMILARITY: Belongs to the uracil-DNA glycosylase (UDG) superfamily.
CC TDG/mug family. {ECO:0000305}.
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DR EMBL; AF069519; AAC31900.1; -; mRNA.
DR EMBL; AK053870; BAC35566.1; -; mRNA.
DR EMBL; AK089915; BAC40994.1; -; mRNA.
DR EMBL; AK164090; BAE37621.1; -; mRNA.
DR EMBL; AK164643; BAE37857.1; -; mRNA.
DR EMBL; AK169768; BAE41355.1; -; mRNA.
DR EMBL; AC152980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466540; EDL04997.1; -; Genomic_DNA.
DR EMBL; BC010315; AAH10315.2; -; mRNA.
DR EMBL; BC085470; AAH85470.1; -; mRNA.
DR EMBL; BC085471; AAH85471.1; -; mRNA.
DR CCDS; CCDS24070.1; -. [P56581-1]
DR CCDS; CCDS36013.1; -. [P56581-2]
DR PIR; A46132; A46132.
DR RefSeq; NP_035691.2; NM_011561.2. [P56581-2]
DR RefSeq; NP_766140.2; NM_172552.3. [P56581-1]
DR AlphaFoldDB; P56581; -.
DR SMR; P56581; -.
DR BioGRID; 204088; 6.
DR DIP; DIP-216N; -.
DR IntAct; P56581; 2.
DR STRING; 10090.ENSMUSP00000121000; -.
DR iPTMnet; P56581; -.
DR PhosphoSitePlus; P56581; -.
DR EPD; P56581; -.
DR PaxDb; P56581; -.
DR PeptideAtlas; P56581; -.
DR PRIDE; P56581; -.
DR ProteomicsDB; 263026; -. [P56581-1]
DR ProteomicsDB; 263027; -. [P56581-2]
DR Antibodypedia; 30563; 418 antibodies from 31 providers.
DR DNASU; 21665; -.
DR Ensembl; ENSMUST00000092266; ENSMUSP00000089917; ENSMUSG00000034674. [P56581-2]
DR Ensembl; ENSMUST00000151390; ENSMUSP00000121000; ENSMUSG00000034674. [P56581-1]
DR GeneID; 21665; -.
DR KEGG; mmu:21665; -.
DR UCSC; uc007gjr.2; mouse. [P56581-1]
DR CTD; 6996; -.
DR MGI; MGI:108247; Tdg.
DR VEuPathDB; HostDB:ENSMUSG00000034674; -.
DR eggNOG; KOG4120; Eukaryota.
DR GeneTree; ENSGT00390000000987; -.
DR HOGENOM; CLU_045775_1_0_1; -.
DR InParanoid; P56581; -.
DR OMA; YCEGSSF; -.
DR OrthoDB; 1209629at2759; -.
DR PhylomeDB; P56581; -.
DR TreeFam; TF328764; -.
DR Reactome; R-MMU-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-MMU-110357; Displacement of DNA glycosylase by APEX1.
DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-MMU-5221030; TET1,2,3 and TDG demethylate DNA.
DR BioGRID-ORCS; 21665; 4 hits in 112 CRISPR screens.
DR ChiTaRS; Tdg; mouse.
DR PRO; PR:P56581; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P56581; protein.
DR Bgee; ENSMUSG00000034674; Expressed in ganglionic eminence and 131 other tissues.
DR ExpressionAtlas; P56581; baseline and differential.
DR Genevisible; P56581; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016605; C:PML body; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0031404; F:chloride ion binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA: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; ISS:UniProtKB.
DR GO; GO:0043739; F:G/U mismatch-specific uracil-DNA glycosylase activity; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0030983; F:mismatched DNA binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IPI:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0008263; F:pyrimidine-specific mismatch base pair DNA N-glycosylase activity; ISO:MGI.
DR GO; GO:0031402; F:sodium ion binding; ISO:MGI.
DR GO; GO:0032183; F:SUMO binding; IPI:MGI.
DR GO; GO:0003712; F:transcription coregulator activity; IGI:MGI.
DR GO; GO:0004844; F:uracil DNA N-glycosylase activity; ISO:MGI.
DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB.
DR GO; GO:0006285; P:base-excision repair, AP site formation; ISO:MGI.
DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB.
DR GO; GO:0006298; P:mismatch repair; ISS:UniProtKB.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IDA:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:1902544; P:regulation of DNA N-glycosylase activity; ISO:MGI.
DR GO; GO:0045995; P:regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB.
DR CDD; cd10028; UDG-F2_TDG_MUG; 1.
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 Activator; Alternative splicing; Chromatin regulator; DNA damage;
KW DNA repair; Hydrolase; Isopeptide bond; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..421
FT /note="G/T mismatch-specific thymine DNA glycosylase"
FT /id="PRO_0000185778"
FT REGION 45..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..108
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 114
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13569"
FT CROSSLNK 259
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13569"
FT CROSSLNK 341
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 341
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q13569"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:9694815"
FT /id="VSP_046491"
FT MUTAGEN 151
FT /note="N->A: Loss of DNA glycosylase activity."
FT /evidence="ECO:0000269|PubMed:21278727,
FT ECO:0000269|PubMed:21722948, ECO:0000269|PubMed:21817016"
FT CONFLICT 57
FT /note="E -> A (in Ref. 1; AAC31900, 2; BAC40994/BAE41355,
FT 4; EDL04997 and 5; AAH10315)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="S -> I (in Ref. 5; AAH85470)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="K -> E (in Ref. 2; BAC35566)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="A -> T (in Ref. 1; AAC31900, 2; BAC40994/BAE41355,
FT 4; EDL04997 and 5; AAH10315)"
FT /evidence="ECO:0000305"
FT CONFLICT 386..388
FT /note="APS -> TPG (in Ref. 1; AAC31900, 2; BAC40994/
FT BAE41355, 4; EDL04997 and 5; AAH10315)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 46879 MW; A91BB0A5911933BC CRC64;
MDAEAARSYS LEQVQALYSF PFQQMMAEVP NMAVTTGQQV PAVAPNMATV TEQQVPEDAP
VQEPAPEAPK RRKRKPRAAE PQEPVEPKKP ATSKKSGKST KSKEKQEKIT DAFKVKRKVD
RFNGVSEAEL LTKTLPDILT FNLDIVIIGI NPGLMAAYKG HHYPGPGNHF WKCLFMSGLS
EVQLNHMDDH TLPGKYGIGF TNMVERTTPG SKDLSSKEFR EGGRILVQKL QKYQPRIAVF
NGKCIYEIFS KEVFGVKVKN LEFGLQPHKI PDTETLCYVM PSSSARCAQF PRAQDKVHYY
IKLKDLRDQL KGIERNADVQ EVQYTFDLQL AQEDAKKMAV KEEKYDPGYE AAYGGAYGEN
PCNGEPCGIA SNGLTAHSAE PRGEAAPSDV PNGQWMAQSF AEQIPSFNNC GTREQEEESH
A
