CPLM-012150

Genbank Nucleotide ID

G/T mismatch-specific thymine DNA glycosylase

Protein Synonyms/Alias

Thymine-DNA glycosylase; hTDG

Homo sapiens (Human)

Position	Peptide	Type	References
71	KPRTTEPKQPVEPKK	ubiquitination	[1]
94	KSAKSKEKQEKITDT	ubiquitination	[1]
97	KSKEKQEKITDTFKV	acetylation	[2]
97	KSKEKQEKITDTFKV	ubiquitination	[1]
103	EKITDTFKVKRKVDR	ubiquitination	[1]
105	ITDTFKVKRKVDRFN	ubiquitination	[1]
107	DTFKVKRKVDRFNGV	ubiquitination	[1]
201	ERTTPGSKDLSSKEF	ubiquitination	[1, 3]
206	GSKDLSSKEFREGGR	ubiquitination	[1, 4]
218	GGRILVQKLQKYQPR	ubiquitination	[1, 4]
221	ILVQKLQKYQPRIAV	ubiquitination	[1, 5, 6]
232	RIAVFNGKCIYEIFS	ubiquitination	[1, 4]
246	SKEVFGVKVKNLEFG	ubiquitination	[1]
248	EVFGVKVKNLEFGLQ	ubiquitination	[1]
258	EFGLQPHKIPDTETL	ubiquitination	[1]
285	QFPRAQDKVHYYIKL	ubiquitination	[1]
291	DKVHYYIKLKDLRDQ	ubiquitination	[1]
293	VHYYIKLKDLRDQLK	ubiquitination	[1]
300	KDLRDQLKGIERNMD	ubiquitination	[1, 4]
330	DAKKMAVKEEKYDPG	sumoylation	[7, 8, 9, 10]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[7] Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover.
Hardeland U, Steinacher R, Jiricny J, Schär P.
EMBO J. 2002 Mar 15;21(6):1456-64. [PMID: 11889051]
[8] Functionality of human thymine DNA glycosylase requires SUMO-regulated changes in protein conformation.
Steinacher R, Schär P.
Curr Biol. 2005 Apr 12;15(7):616-23. [PMID: 15823533]
[9] Crystal structure of thymine DNA glycosylase conjugated to SUMO-1.
Baba D, Maita N, Jee JG, Uchimura Y, Saitoh H, Sugasawa K, Hanaoka F, Tochio H, Hiroaki H, Shirakawa M.
Nature. 2005 Jun 16;435(7044):979-82. [PMID: 15959518]
[10] SUMO-1 regulates the conformational dynamics of thymine-DNA Glycosylase regulatory domain and competes with its DNA binding activity.
Smet-Nocca C, Wieruszeski JM, Léger H, Eilebrecht S, Benecke A.
BMC Biochem. 2011 Feb 1;12:4. [PMID: 21284855]

Functional Description

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.

CROSSLNK 330 330 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Activator; Chromatin regulator; Complete proteome; Direct protein sequencing; DNA damage; DNA repair; Glycosidase; Hydrolase; Isopeptide bond; Nucleus; Polymorphism; Reference proteome; Transcription; Transcription regulation; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0016605; C:PML body; IEA:Compara.
GO:0003684; F:damaged DNA binding; TAS:ProtInc.
GO:0030983; F:mismatched DNA binding; IDA:UniProtKB.
GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
GO:0008263; F:pyrimidine-specific mismatch base pair DNA N-glycosylase activity; IDA:UniProtKB.
GO:0001104; F:RNA polymerase II transcription cofactor activity; IEA:Compara.
GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
GO:0045008; P:depyrimidination; TAS:Reactome.
GO:0080111; P:DNA demethylation; ISS:UniProtKB.
GO:0009790; P:embryo development; ISS:UniProtKB.
GO:0006298; P:mismatch repair; IDA:UniProtKB.
GO:0035562; P:negative regulation of chromatin binding; IEA:Compara.
GO:0032091; P:negative regulation of protein binding; IEA:Compara.
GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.

IPR015637; DNA_glycosylase_G/T-mismatch.
IPR003310; Thymine-DNA_glycosylase.
IPR005122; Uracil-DNA_glycosylase-like.