Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

G/T mismatch-specific thymine DNA glycosylase

Gene

TDG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA glycosylase that plays a key role in active DNA demethylation: specifically recognizes and binds 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates their excision through base-excision repair (BER) to install an unmethylated cytosine. Cannot remove 5-hydroxymethylcytosine (5hmC). According to an alternative model, involved in DNA demethylation by mediating DNA glycolase activity toward 5-hydroxymethyluracil (5hmU) produced by deamination of 5hmC. Also involved in DNA repair by acting as a thymine-DNA glycosylase that mediates correction of G/T mispairs to G/C pairs: in the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. Its role in the repair of canonical base damage is however minor compared to its role in DNA demethylation. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine.7 Publications

Catalytic activityi

Hydrolyzes mismatched double-stranded DNA and polynucleotides, releasing free thymine.

GO - Molecular functioni

  • damaged DNA binding Source: ProtInc
  • DNA N-glycosylase activity Source: UniProtKB
  • double-stranded DNA binding Source: UniProtKB
  • mismatched DNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • pyrimidine-specific mismatch base pair DNA N-glycosylase activity Source: UniProtKB
  • RNA polymerase II transcription cofactor activity Source: Ensembl
  • structure-specific DNA binding Source: UniProtKB
  • uracil DNA N-glycosylase activity Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Glycosidase, Hydrolase

Keywords - Biological processi

DNA damage, DNA repair, Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139372-MONOMER.
BRENDAi3.2.2.29. 2681.
ReactomeiR-HSA-110328. Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
R-HSA-110329. Cleavage of the damaged pyrimidine.
R-HSA-110357. Displacement of DNA glycosylase by APEX1.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-5221030. TET1,2,3 and TDG demethylate DNA.

Names & Taxonomyi

Protein namesi
Recommended name:
G/T mismatch-specific thymine DNA glycosylase (EC:3.2.2.29)
Alternative name(s):
Thymine-DNA glycosylase
Short name:
hTDG
Gene namesi
Name:TDG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11700. TDG.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • PML body Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140N → A: Loss of DNA glycosylase activity but still able to bind DNA. 1 Publication1
Mutagenesisi145A → G: Increased DNA glycosylase activity on G/T mispairs. 1 Publication1
Mutagenesisi151H → A or Q: Increased DNA glycosylase activity on G/T mispairs. 1 Publication1
Mutagenesisi191N → A: Reduced DNA glycosylase activity on G/T and G/U mispairs. 1 Publication1
Mutagenesisi197T → A: Reduced DNA glycosylase activity on G/T mispairs. 1 Publication1
Mutagenesisi281R → A: Restores the DNA-binding ability of the sumoylated form. 1 Publication1
Mutagenesisi310E → Q: Restores the DNA-binding ability of the sumoylated form. 2 Publications1
Mutagenesisi315F → A: Restores the DNA-binding ability of the sumoylated form. 1 Publication1

Organism-specific databases

DisGeNETi6996.
OpenTargetsiENSG00000139372.
PharmGKBiPA36419.

Polymorphism and mutation databases

BioMutaiTDG.
DMDMi46397791.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001857771 – 410G/T mismatch-specific thymine DNA glycosylaseAdd BLAST410

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki330Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki330Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources

Post-translational modificationi

Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces dissociation of the product DNA.1 Publication

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ13569.
MaxQBiQ13569.
PaxDbiQ13569.
PeptideAtlasiQ13569.
PRIDEiQ13569.

PTM databases

iPTMnetiQ13569.
PhosphoSitePlusiQ13569.

Expressioni

Gene expression databases

BgeeiENSG00000139372.
CleanExiHS_TDG.
ExpressionAtlasiQ13569. baseline and differential.
GenevisibleiQ13569. HS.

Organism-specific databases

HPAiHPA052263.

Interactioni

Subunit structurei

Homodimer. Interacts with AICDA and GADD45A.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AICDAQ9GZX75EBI-348333,EBI-3834328
GADD45AP245223EBI-348333,EBI-448167

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi112855. 37 interactors.
DIPiDIP-32709N.
IntActiQ13569. 13 interactors.
MINTiMINT-1182514.
STRINGi9606.ENSP00000376611.

Structurei

Secondary structure

1410
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni111 – 113Combined sources3
Helixi116 – 119Combined sources4
Beta strandi133 – 139Combined sources7
Helixi143 – 148Combined sources6
Beta strandi150 – 152Combined sources3
Beta strandi154 – 157Combined sources4
Helixi159 – 165Combined sources7
Beta strandi168 – 171Combined sources4
Helixi175 – 180Combined sources6
Helixi181 – 185Combined sources5
Beta strandi186 – 192Combined sources7
Helixi200 – 202Combined sources3
Helixi205 – 222Combined sources18
Beta strandi225 – 231Combined sources7
Helixi232 – 243Combined sources12
Beta strandi252 – 254Combined sources3
Beta strandi265 – 269Combined sources5
Beta strandi272 – 274Combined sources3
Beta strandi277 – 279Combined sources3
Helixi282 – 304Combined sources23
Beta strandi308 – 314Combined sources7
Helixi317 – 329Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WYWX-ray2.10A112-339[»]
2D07X-ray2.10A112-339[»]
2RBAX-ray2.79A/B111-308[»]
3UFJX-ray2.97A/B111-308[»]
3UO7X-ray3.00A/B111-308[»]
3UOBX-ray3.01A/B111-308[»]
4FNCX-ray2.49A111-308[»]
4JGCX-ray2.58A111-308[»]
4XEGX-ray1.72A111-308[»]
4Z3AX-ray1.72A111-308[»]
4Z47X-ray1.45A111-308[»]
4Z7BX-ray2.02A111-308[»]
4Z7ZX-ray1.83A111-308[»]
5CYSX-ray2.45A111-308[»]
5FF8X-ray1.70A82-308[»]
5HF7X-ray1.54A82-308[»]
5JXYX-ray1.71A111-308[»]
DisProtiDP00719.
ProteinModelPortaliQ13569.
SMRiQ13569.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13569.

Family & Domainsi

Sequence similaritiesi

Belongs to the TDG/mug DNA glycosylase family.Curated

Phylogenomic databases

eggNOGiKOG4120. Eukaryota.
COG3663. LUCA.
GeneTreeiENSGT00390000000987.
HOGENOMiHOG000220820.
HOVERGENiHBG003685.
InParanoidiQ13569.
KOiK20813.
OMAiVPNGQWM.
OrthoDBiEOG091G0N58.
PhylomeDBiQ13569.
TreeFamiTF328764.

Family and domain databases

CDDicd10028. UDG_F2_MUG. 1 hit.
Gene3Di3.40.470.10. 1 hit.
InterProiIPR015637. MUG/TDG.
IPR003310. TDG.
IPR005122. Uracil-DNA_glycosylase-like.
[Graphical view]
PANTHERiPTHR12159. PTHR12159. 1 hit.
PfamiPF03167. UDG. 1 hit.
[Graphical view]
SUPFAMiSSF52141. SSF52141. 1 hit.
TIGRFAMsiTIGR00584. mug. 1 hit.

Sequencei

Sequence statusi: Complete.

Q13569-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAENAGSYS LQQAQAFYTF PFQQLMAEAP NMAVVNEQQM PEEVPAPAPA
60 70 80 90 100
QEPVQEAPKG RKRKPRTTEP KQPVEPKKPV ESKKSGKSAK SKEKQEKITD
110 120 130 140 150
TFKVKRKVDR FNGVSEAELL TKTLPDILTF NLDIVIIGIN PGLMAAYKGH
160 170 180 190 200
HYPGPGNHFW KCLFMSGLSE VQLNHMDDHT LPGKYGIGFT NMVERTTPGS
210 220 230 240 250
KDLSSKEFRE GGRILVQKLQ KYQPRIAVFN GKCIYEIFSK EVFGVKVKNL
260 270 280 290 300
EFGLQPHKIP DTETLCYVMP SSSARCAQFP RAQDKVHYYI KLKDLRDQLK
310 320 330 340 350
GIERNMDVQE VQYTFDLQLA QEDAKKMAVK EEKYDPGYEA AYGGAYGENP
360 370 380 390 400
CSSEPCGFSS NGLIESVELR GESAFSGIPN GQWMTQSFTD QIPSFSNHCG
410
TQEQEEESHA
Length:410
Mass (Da):46,053
Last modified:April 13, 2004 - v2
Checksum:i33752B26EBC789AE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti91S → P in AAC50540 (PubMed:8662714).Curated1
Sequence conflicti268V → G in AAH37557 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018892199G → S.1 PublicationCorresponds to variant rs4135113dbSNPEnsembl.1
Natural variantiVAR_059450367V → L.Corresponds to variant rs2888805dbSNPEnsembl.1
Natural variantiVAR_018893367V → M.1 PublicationCorresponds to variant rs2888805dbSNPEnsembl.1
Natural variantiVAR_050140381G → E.Corresponds to variant rs3953597dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51166 mRNA. Translation: AAC50540.1.
AF545435 Genomic DNA. Translation: AAN16399.1.
AC078819 Genomic DNA. No translation available.
BC037557 mRNA. Translation: AAH37557.1.
CCDSiCCDS9095.1.
RefSeqiNP_003202.3. NM_003211.4.
UniGeneiHs.584809.

Genome annotation databases

EnsembliENST00000392872; ENSP00000376611; ENSG00000139372.
GeneIDi6996.
KEGGihsa:6996.
UCSCiuc001tkg.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51166 mRNA. Translation: AAC50540.1.
AF545435 Genomic DNA. Translation: AAN16399.1.
AC078819 Genomic DNA. No translation available.
BC037557 mRNA. Translation: AAH37557.1.
CCDSiCCDS9095.1.
RefSeqiNP_003202.3. NM_003211.4.
UniGeneiHs.584809.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WYWX-ray2.10A112-339[»]
2D07X-ray2.10A112-339[»]
2RBAX-ray2.79A/B111-308[»]
3UFJX-ray2.97A/B111-308[»]
3UO7X-ray3.00A/B111-308[»]
3UOBX-ray3.01A/B111-308[»]
4FNCX-ray2.49A111-308[»]
4JGCX-ray2.58A111-308[»]
4XEGX-ray1.72A111-308[»]
4Z3AX-ray1.72A111-308[»]
4Z47X-ray1.45A111-308[»]
4Z7BX-ray2.02A111-308[»]
4Z7ZX-ray1.83A111-308[»]
5CYSX-ray2.45A111-308[»]
5FF8X-ray1.70A82-308[»]
5HF7X-ray1.54A82-308[»]
5JXYX-ray1.71A111-308[»]
DisProtiDP00719.
ProteinModelPortaliQ13569.
SMRiQ13569.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112855. 37 interactors.
DIPiDIP-32709N.
IntActiQ13569. 13 interactors.
MINTiMINT-1182514.
STRINGi9606.ENSP00000376611.

PTM databases

iPTMnetiQ13569.
PhosphoSitePlusiQ13569.

Polymorphism and mutation databases

BioMutaiTDG.
DMDMi46397791.

Proteomic databases

EPDiQ13569.
MaxQBiQ13569.
PaxDbiQ13569.
PeptideAtlasiQ13569.
PRIDEiQ13569.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000392872; ENSP00000376611; ENSG00000139372.
GeneIDi6996.
KEGGihsa:6996.
UCSCiuc001tkg.4. human.

Organism-specific databases

CTDi6996.
DisGeNETi6996.
GeneCardsiTDG.
H-InvDBHIX0026376.
HGNCiHGNC:11700. TDG.
HPAiHPA052263.
MIMi601423. gene.
neXtProtiNX_Q13569.
OpenTargetsiENSG00000139372.
PharmGKBiPA36419.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4120. Eukaryota.
COG3663. LUCA.
GeneTreeiENSGT00390000000987.
HOGENOMiHOG000220820.
HOVERGENiHBG003685.
InParanoidiQ13569.
KOiK20813.
OMAiVPNGQWM.
OrthoDBiEOG091G0N58.
PhylomeDBiQ13569.
TreeFamiTF328764.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139372-MONOMER.
BRENDAi3.2.2.29. 2681.
ReactomeiR-HSA-110328. Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
R-HSA-110329. Cleavage of the damaged pyrimidine.
R-HSA-110357. Displacement of DNA glycosylase by APEX1.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-5221030. TET1,2,3 and TDG demethylate DNA.

Miscellaneous databases

ChiTaRSiTDG. human.
EvolutionaryTraceiQ13569.
GeneWikiiThymine-DNA_glycosylase.
GenomeRNAii6996.
PROiQ13569.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139372.
CleanExiHS_TDG.
ExpressionAtlasiQ13569. baseline and differential.
GenevisibleiQ13569. HS.

Family and domain databases

CDDicd10028. UDG_F2_MUG. 1 hit.
Gene3Di3.40.470.10. 1 hit.
InterProiIPR015637. MUG/TDG.
IPR003310. TDG.
IPR005122. Uracil-DNA_glycosylase-like.
[Graphical view]
PANTHERiPTHR12159. PTHR12159. 1 hit.
PfamiPF03167. UDG. 1 hit.
[Graphical view]
SUPFAMiSSF52141. SSF52141. 1 hit.
TIGRFAMsiTIGR00584. mug. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTDG_HUMAN
AccessioniPrimary (citable) accession number: Q13569
Secondary accession number(s): Q8IUZ6, Q8IZM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 13, 2004
Last modified: November 30, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.