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Protein

G/T mismatch-specific thymine DNA glycosylase

Gene

TDG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Hydrolase
Biological processDNA damage, DNA repair, Transcription, Transcription regulation

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000139372.14
HGNCiHGNC:11700 TDG
MIMi601423 gene
neXtProtiNX_Q13569

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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-linki103Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki248Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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
ProteomicsDBi59573

PTM databases

iPTMnetiQ13569
PhosphoSitePlusiQ13569

Expressioni

Gene expression databases

BgeeiENSG00000139372 Expressed in 233 organ(s), highest expression level in forebrain
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112855, 40 interactors
DIPiDIP-32709N
ELMiQ13569
IntActiQ13569, 14 interactors
MINTiQ13569
STRINGi9606.ENSP00000376611

Structurei

Secondary structure

1410
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00719
ProteinModelPortaliQ13569
SMRiQ13569
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13569

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

CDDicd10028 UDG_F2_MUG, 1 hit
Gene3Di3.40.470.10, 1 hit
InterProiView protein in InterPro
IPR015637 MUG/TDG
IPR003310 TDG
IPR005122 Uracil-DNA_glycosylase-like
IPR036895 Uracil-DNA_glycosylase-like_sf
PANTHERiPTHR12159 PTHR12159, 1 hit
PfamiView protein in Pfam
PF03167 UDG, 1 hit
SUPFAMiSSF52141 SSF52141, 1 hit
TIGRFAMsiTIGR00584 mug, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4E127B4E127_HUMAN
G/T mismatch-specific thymine DNA g...
TDG
267Annotation score:
G8JL98G8JL98_HUMAN
G/T mismatch-specific thymine DNA g...
TDG
406Annotation score:
F5H0I7F5H0I7_HUMAN
G/T mismatch-specific thymine DNA g...
TDG
257Annotation score:
H0YH18H0YH18_HUMAN
G/T mismatch-specific thymine DNA g...
TDG
111Annotation score:
F5H539F5H539_HUMAN
G/T mismatch-specific thymine DNA g...
TDG
138Annotation score:

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 → S1 PublicationCorresponds to variant dbSNP:rs4135113Ensembl.1
Natural variantiVAR_059450367V → L. Corresponds to variant dbSNP:rs2888805Ensembl.1
Natural variantiVAR_018893367V → M1 PublicationCorresponds to variant dbSNP:rs2888805Ensembl.1
Natural variantiVAR_050140381G → E. Corresponds to variant dbSNP:rs3953597Ensembl.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

Similar proteinsi

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[»]
5T2WX-ray2.20A82-308[»]
DisProtiDP00719
ProteinModelPortaliQ13569
SMRiQ13569
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112855, 40 interactors
DIPiDIP-32709N
ELMiQ13569
IntActiQ13569, 14 interactors
MINTiQ13569
STRINGi9606.ENSP00000376611

PTM databases

iPTMnetiQ13569
PhosphoSitePlusiQ13569

Polymorphism and mutation databases

BioMutaiTDG
DMDMi46397791

Proteomic databases

EPDiQ13569
MaxQBiQ13569
PaxDbiQ13569
PeptideAtlasiQ13569
PRIDEiQ13569
ProteomicsDBi59573

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6996
DisGeNETi6996
EuPathDBiHostDB:ENSG00000139372.14
GeneCardsiTDG
H-InvDBiHIX0026376
HGNCiHGNC:11700 TDG
HPAiHPA052263
MIMi601423 gene
neXtProtiNX_Q13569
OpenTargetsiENSG00000139372
PharmGKBiPA36419
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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
PROiPR:Q13569
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139372 Expressed in 233 organ(s), highest expression level in forebrain
CleanExiHS_TDG
ExpressionAtlasiQ13569 baseline and differential
GenevisibleiQ13569 HS

Family and domain databases

CDDicd10028 UDG_F2_MUG, 1 hit
Gene3Di3.40.470.10, 1 hit
InterProiView protein in InterPro
IPR015637 MUG/TDG
IPR003310 TDG
IPR005122 Uracil-DNA_glycosylase-like
IPR036895 Uracil-DNA_glycosylase-like_sf
PANTHERiPTHR12159 PTHR12159, 1 hit
PfamiView protein in Pfam
PF03167 UDG, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 13, 2004
Last modified: November 7, 2018
This is version 168 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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