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Protein

G/T mismatch-specific thymine DNA glycosylase

Gene

Tdg

Organism
Mus musculus (Mouse)
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 (PubMed:21817016). 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 (PubMed:21722948). 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.3 Publications

Catalytic activityi

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

GO - Molecular functioni

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

GO - Biological processi

  • base-excision repair Source: UniProtKB
  • base-excision repair, AP site formation Source: GO_Central
  • chromatin modification Source: UniProtKB-KW
  • DNA demethylation Source: UniProtKB
  • embryo development Source: UniProtKB
  • mismatch repair Source: UniProtKB
  • negative regulation of chromatin binding Source: MGI
  • negative regulation of protein binding Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of gene expression, epigenetic Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
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

ReactomeiR-MMU-110329. Cleavage of the damaged pyrimidine.
R-MMU-110357. Displacement of DNA glycosylase by APEX1.
R-MMU-3108214. SUMOylation of DNA damage response and repair proteins.
R-MMU-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):
C-JUN leucine zipper interactive protein JZA-3
Thymine-DNA glycosylase
Gene namesi
Name:Tdg
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:108247. Tdg.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality between embryonic day (E) 10.5 and E12.5. Embryos display specific patterning defects of the developing heart; vasculogenesis defects of dorsal aortae, carotid arteries and branchial arteries. Global defects of angiogenesis are also oberved. Defects are due to epigenetic aberrations affecting the expression of developmental genes, coincident with imbalanced histone modification and CpG methylation at promoters of affected genes.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi151N → A: Loss of DNA glycosylase activity. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001857781 – 421G/T mismatch-specific thymine DNA glycosylaseAdd BLAST421

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki341Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki341Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity

Post-translational modificationi

Sumoylation on Lys-341 by either SUMO1 or SUMO2 induces dissociation of the product DNA.By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiP56581.
PeptideAtlasiP56581.
PRIDEiP56581.

PTM databases

iPTMnetiP56581.
PhosphoSitePlusiP56581.

Expressioni

Gene expression databases

BgeeiENSMUSG00000034674.
CleanExiMM_TDG.
ExpressionAtlasiP56581. baseline and differential.
GenevisibleiP56581. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with AICDA and GADD45A (By similarity).By similarity

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • protein kinase C binding Source: MGI
  • SUMO binding Source: MGI

Protein-protein interaction databases

BioGridi204088. 4 interactors.
DIPiDIP-216N.
IntActiP56581. 1 interactor.
STRINGi10090.ENSMUSP00000121000.

Structurei

3D structure databases

ProteinModelPortaliP56581.
SMRiP56581.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TDG/mug DNA glycosylase family.Curated

Phylogenomic databases

eggNOGiKOG4120. Eukaryota.
COG3663. LUCA.
GeneTreeiENSGT00390000000987.
HOGENOMiHOG000220820.
HOVERGENiHBG003685.
InParanoidiP56581.
KOiK20813.
OMAiVPNGQWM.
OrthoDBiEOG091G0N58.
PhylomeDBiP56581.
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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P56581-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDAEAARSYS LEQVQALYSF PFQQMMAEVP NMAVTTGQQV PAVAPNMATV
60 70 80 90 100
TEQQVPEDAP VQEPAPEAPK RRKRKPRAAE PQEPVEPKKP ATSKKSGKST
110 120 130 140 150
KSKEKQEKIT DAFKVKRKVD RFNGVSEAEL LTKTLPDILT FNLDIVIIGI
160 170 180 190 200
NPGLMAAYKG HHYPGPGNHF WKCLFMSGLS EVQLNHMDDH TLPGKYGIGF
210 220 230 240 250
TNMVERTTPG SKDLSSKEFR EGGRILVQKL QKYQPRIAVF NGKCIYEIFS
260 270 280 290 300
KEVFGVKVKN LEFGLQPHKI PDTETLCYVM PSSSARCAQF PRAQDKVHYY
310 320 330 340 350
IKLKDLRDQL KGIERNADVQ EVQYTFDLQL AQEDAKKMAV KEEKYDPGYE
360 370 380 390 400
AAYGGAYGEN PCNGEPCGIA SNGLTAHSAE PRGEAAPSDV PNGQWMAQSF
410 420
AEQIPSFNNC GTREQEEESH A
Length:421
Mass (Da):46,879
Last modified:May 1, 2013 - v2
Checksum:iA91BB0A5911933BC
GO
Isoform 2 (identifier: P56581-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.

Show »
Length:397
Mass (Da):44,117
Checksum:i51205551C2046AB5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57E → A in AAC31900 (PubMed:9694815).Curated1
Sequence conflicti57E → A in BAC40994 (PubMed:16141072).Curated1
Sequence conflicti57E → A in BAE41355 (PubMed:16141072).Curated1
Sequence conflicti57E → A in EDL04997 (Ref. 4) Curated1
Sequence conflicti57E → A in AAH10315 (PubMed:15489334).Curated1
Sequence conflicti216S → I in AAH85470 (PubMed:15489334).Curated1
Sequence conflicti232K → E in BAC35566 (PubMed:16141072).Curated1
Sequence conflicti317A → T in AAC31900 (PubMed:9694815).Curated1
Sequence conflicti317A → T in BAC40994 (PubMed:16141072).Curated1
Sequence conflicti317A → T in BAE41355 (PubMed:16141072).Curated1
Sequence conflicti317A → T in EDL04997 (Ref. 4) Curated1
Sequence conflicti317A → T in AAH10315 (PubMed:15489334).Curated1
Sequence conflicti386 – 388APS → TPG in AAC31900 (PubMed:9694815).Curated3
Sequence conflicti386 – 388APS → TPG in BAC40994 (PubMed:16141072).Curated3
Sequence conflicti386 – 388APS → TPG in BAE41355 (PubMed:16141072).Curated3
Sequence conflicti386 – 388APS → TPG in EDL04997 (Ref. 4) Curated3
Sequence conflicti386 – 388APS → TPG in AAH10315 (PubMed:15489334).Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0464911 – 24Missing in isoform 2. 2 PublicationsAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF069519 mRNA. Translation: AAC31900.1.
AK053870 mRNA. Translation: BAC35566.1.
AK089915 mRNA. Translation: BAC40994.1.
AK164090 mRNA. Translation: BAE37621.1.
AK164643 mRNA. Translation: BAE37857.1.
AK169768 mRNA. Translation: BAE41355.1.
AC152980 Genomic DNA. No translation available.
CH466540 Genomic DNA. Translation: EDL04997.1.
BC010315 mRNA. Translation: AAH10315.2.
BC085470 mRNA. Translation: AAH85470.1.
BC085471 mRNA. Translation: AAH85471.1.
CCDSiCCDS24070.1. [P56581-1]
CCDS36013.1. [P56581-2]
PIRiA46132.
RefSeqiNP_035691.2. NM_011561.2. [P56581-2]
NP_766140.2. NM_172552.3. [P56581-1]
UniGeneiMm.284252.
Mm.347607.

Genome annotation databases

EnsembliENSMUST00000092266; ENSMUSP00000089917; ENSMUSG00000034674. [P56581-2]
ENSMUST00000151390; ENSMUSP00000121000; ENSMUSG00000034674. [P56581-1]
GeneIDi21665.
KEGGimmu:21665.
UCSCiuc007gjr.2. mouse. [P56581-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF069519 mRNA. Translation: AAC31900.1.
AK053870 mRNA. Translation: BAC35566.1.
AK089915 mRNA. Translation: BAC40994.1.
AK164090 mRNA. Translation: BAE37621.1.
AK164643 mRNA. Translation: BAE37857.1.
AK169768 mRNA. Translation: BAE41355.1.
AC152980 Genomic DNA. No translation available.
CH466540 Genomic DNA. Translation: EDL04997.1.
BC010315 mRNA. Translation: AAH10315.2.
BC085470 mRNA. Translation: AAH85470.1.
BC085471 mRNA. Translation: AAH85471.1.
CCDSiCCDS24070.1. [P56581-1]
CCDS36013.1. [P56581-2]
PIRiA46132.
RefSeqiNP_035691.2. NM_011561.2. [P56581-2]
NP_766140.2. NM_172552.3. [P56581-1]
UniGeneiMm.284252.
Mm.347607.

3D structure databases

ProteinModelPortaliP56581.
SMRiP56581.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204088. 4 interactors.
DIPiDIP-216N.
IntActiP56581. 1 interactor.
STRINGi10090.ENSMUSP00000121000.

PTM databases

iPTMnetiP56581.
PhosphoSitePlusiP56581.

Proteomic databases

PaxDbiP56581.
PeptideAtlasiP56581.
PRIDEiP56581.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000092266; ENSMUSP00000089917; ENSMUSG00000034674. [P56581-2]
ENSMUST00000151390; ENSMUSP00000121000; ENSMUSG00000034674. [P56581-1]
GeneIDi21665.
KEGGimmu:21665.
UCSCiuc007gjr.2. mouse. [P56581-1]

Organism-specific databases

CTDi6996.
MGIiMGI:108247. Tdg.

Phylogenomic databases

eggNOGiKOG4120. Eukaryota.
COG3663. LUCA.
GeneTreeiENSGT00390000000987.
HOGENOMiHOG000220820.
HOVERGENiHBG003685.
InParanoidiP56581.
KOiK20813.
OMAiVPNGQWM.
OrthoDBiEOG091G0N58.
PhylomeDBiP56581.
TreeFamiTF328764.

Enzyme and pathway databases

ReactomeiR-MMU-110329. Cleavage of the damaged pyrimidine.
R-MMU-110357. Displacement of DNA glycosylase by APEX1.
R-MMU-3108214. SUMOylation of DNA damage response and repair proteins.
R-MMU-5221030. TET1,2,3 and TDG demethylate DNA.

Miscellaneous databases

PROiP56581.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034674.
CleanExiMM_TDG.
ExpressionAtlasiP56581. baseline and differential.
GenevisibleiP56581. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P56581
Secondary accession number(s): Q3TPW4
, Q542A9, Q5U3M4, Q5U3M5, Q6PJW4, Q8BPK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 1, 2013
Last modified: November 30, 2016
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.