dbPTM

TDG_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	TDG_HUMAN
UniProt AC	Q13569
Protein Name	G/T mismatch-specific thymine DNA glycosylase
Gene Name	TDG
Organism	Homo sapiens (Human).
Sequence Length	410
Subcellular Localization	Nucleus .
Protein 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..
Protein Sequence	MEAENAGSYSLQQAQAFYTFPFQQLMAEAPNMAVVNEQQMPEEVPAPAPAQEPVQEAPKGRKRKPRTTEPKQPVEPKKPVESKKSGKSAKSKEKQEKITDTFKVKRKVDRFNGVSEAELLTKTLPDILTFNLDIVIIGINPGLMAAYKGHHYPGPGNHFWKCLFMSGLSEVQLNHMDDHTLPGKYGIGFTNMVERTTPGSKDLSSKEFREGGRILVQKLQKYQPRIAVFNGKCIYEIFSKEVFGVKVKNLEFGLQPHKIPDTETLCYVMPSSSARCAQFPRAQDKVHYYIKLKDLRDQLKGIERNMDVQEVQYTFDLQLAQEDAKKMAVKEEKYDPGYEAAYGGAYGENPCSSEPCGFSSNGLIESVELRGESAFSGIPNGQWMTQSFTDQIPSFSNHCGTQEQEEESHA

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
59	Acetylation	EPVQEAPKGRKRKPR CCCCCCCCCCCCCCC	77.67	11864601
67	Phosphorylation	GRKRKPRTTEPKQPV CCCCCCCCCCCCCCC	44.00	22210691
68	Phosphorylation	RKRKPRTTEPKQPVE CCCCCCCCCCCCCCC	52.12	22210691
71	Ubiquitination	KPRTTEPKQPVEPKK CCCCCCCCCCCCCCC	62.09	-
82	Phosphorylation	EPKKPVESKKSGKSA CCCCCCCCCCCCCCC	45.69	-
83	Acetylation	PKKPVESKKSGKSAK CCCCCCCCCCCCCCC	37.14	11864601
84	Acetylation	KKPVESKKSGKSAKS CCCCCCCCCCCCCCC	73.96	11864601
85	Phosphorylation	KPVESKKSGKSAKSK CCCCCCCCCCCCCCH	56.01	-
87	Acetylation	VESKKSGKSAKSKEK CCCCCCCCCCCCHHH	55.09	60417
92	Acetylation	SGKSAKSKEKQEKIT CCCCCCCHHHHHHHC	69.12	7374205
94	Ubiquitination	KSAKSKEKQEKITDT CCCCCHHHHHHHCHH	68.44	-
94	Acetylation	KSAKSKEKQEKITDT CCCCCHHHHHHHCHH	68.44	7374215
97	Acetylation	KSKEKQEKITDTFKV CCHHHHHHHCHHHHH	48.70	20167786
97	Ubiquitination	KSKEKQEKITDTFKV CCHHHHHHHCHHHHH	48.70	-
103	Ubiquitination	EKITDTFKVKRKVDR HHHCHHHHHHHHHHC	49.27	-
103	Sumoylation	EKITDTFKVKRKVDR HHHCHHHHHHHHHHC	49.27	28112733
105	Ubiquitination	ITDTFKVKRKVDRFN HCHHHHHHHHHHCCC	47.28	-
107	Ubiquitination	DTFKVKRKVDRFNGV HHHHHHHHHHCCCCC	42.65	-
185	Phosphorylation	DHTLPGKYGIGFTNM CCCCCCCCEEECCCC	21.64	-
201	Ubiquitination	ERTTPGSKDLSSKEF EECCCCCCCCCCHHH	69.47	21890473
206	Ubiquitination	GSKDLSSKEFREGGR CCCCCCCHHHHHHHH	58.45	-
218	Ubiquitination	GGRILVQKLQKYQPR HHHHHHHHHHHCCCE	45.46	-
221	Ubiquitination	ILVQKLQKYQPRIAV HHHHHHHHCCCEEEE	57.18	21890473
232	Ubiquitination	RIAVFNGKCIYEIFS EEEEECCEEHHHHCC	20.68	-
239	Phosphorylation	KCIYEIFSKEVFGVK EEHHHHCCHHHCCEE	33.30	24719451
246	Ubiquitination	SKEVFGVKVKNLEFG CHHHCCEEEEEECCC	48.12	-
248	Sumoylation	EVFGVKVKNLEFGLQ HHCCEEEEEECCCCC	50.53	28112733
248	Ubiquitination	EVFGVKVKNLEFGLQ HHCCEEEEEECCCCC	50.53	-
248	Sumoylation	EVFGVKVKNLEFGLQ HHCCEEEEEECCCCC	50.53	-
258	Ubiquitination	EFGLQPHKIPDTETL CCCCCCCCCCCCCCE	63.72	-
285	Ubiquitination	QFPRAQDKVHYYIKL CCCCCHHCEEEEEEH	20.87	-
291	Ubiquitination	DKVHYYIKLKDLRDQ HCEEEEEEHHHHHHH	33.10	-
293	Ubiquitination	VHYYIKLKDLRDQLK EEEEEEHHHHHHHHH	50.11	-
300	Ubiquitination	KDLRDQLKGIERNMD HHHHHHHHHHHHCCC	52.81	-
330	Sumoylation	DAKKMAVKEEKYDPG HHHHHHHHHHHCCCC	51.09	28112733
330	Sumoylation	DAKKMAVKEEKYDPG HHHHHHHHHHHCCCC	51.09	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
-	K	Ubiquitination	E3 ubiquitin ligase	DTL	Q9NZJ0	PMID:24962565

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
330	K	Sumoylation		11889051
Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces dissociation of the product DNA.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
185	Phosphorylation	176 (9)	M ⇒ V	rs140436257	Glucagon levels in response to oral glucose tolerance test (fasting)	29093273

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ESR1_HUMAN	ESR1	physical	12874288
GCR_HUMAN	NR3C1	physical	12874288
RARA_HUMAN	RARA	physical	12874288
RXRA_HUMAN	RXRA	physical	12874288
THA_HUMAN	THRA	physical	12874288
ANDR_HUMAN	AR	physical	12874288
VDR_HUMAN	VDR	physical	12874288
PRGR_HUMAN	PGR	physical	12874288
P53_HUMAN	TP53	physical	10961991
P73_HUMAN	TP73	physical	10961991
SUMO1_HUMAN	SUMO1	physical	10961991
SUMO1_HUMAN	SUMO1	physical	11889051
SUMO3_HUMAN	SUMO3	physical	11889051
SUMO1_HUMAN	SUMO1	physical	21284855
SUMO1_HUMAN	SUMO1	physical	16763556
PML_HUMAN	PML	physical	17060459
RNF4_HUMAN	RNF4	physical	20696907
PCNA_HUMAN	PCNA	physical	24962565
DTL_HUMAN	DTL	physical	24962565
ITF2_HUMAN	TCF4	physical	24532795
CBP_HUMAN	CREBBP	physical	24532795
RARA_HUMAN	RARA	physical	24394593
CBP_HUMAN	CREBBP	physical	24394593
XPC_HUMAN	XPC	physical	12505994
CBP_HUMAN	CREBBP	physical	11864601
KDM6B_HUMAN	KDM6B	physical	26544625
FANCA_HUMAN	FANCA	physical	28215707

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of TDG_HUMAN

Related Literatures of Post-Translational Modification

Sumoylation
Reference	PubMed
"Modification of the human thymine-DNA glycosylase by ubiquitin-likeproteins facilitates enzymatic turnover."; Hardeland U., Steinacher R., Jiricny J., Schaer P.; EMBO J. 21:1456-1464(2002). Cited for: SUMOYLATION AT LYS-330.	11889051 [Abstract]

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