TYDP2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TYDP2_HUMAN
• UniProt AC: O95551
• Protein Name: Tyrosyl-DNA phosphodiesterase 2
• Gene Name: TDP2
• Organism: Homo sapiens (Human).
• Sequence Length: 362
• Subcellular Localization: Nucleus. Nucleus, PML body. Nucleus, nucleolus. Cytoplasm. Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein.; Cytoplasm . (Microbial infection) In case of infection by picornavirus, relocali
• Protein Description: DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation.; (Microbial infection) Also acts as a 5'-tyrosyl-RNA phosphodiesterase following picornavirus infection: its activity is hijacked by picornavirus and acts by specifically cleaving the protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection, without impairing the integrity of viral RNA..
• Protein Sequence: MELGSCLEGGREAAEEEGEPEVKKRRLLCVEFASVASCDAAVAQCFLAENDWEMERALNSYFEPPVEESALERRPETISEPKTYVDLTNEETTDSTTSKISPSEDTQQENGSMFSLITWNIDGLDLNNLSERARGVCSYLALYSPDVIFLQEVIPPYYSYLKKRSSNYEIITGHEEGYFTAIMLKKSRVKLKSQEIIPFPSTKMMRNLLCVHVNVSGNELCLMTSHLESTRGHAAERMNQLKMVLKKMQEAPESATVIFAGDTNLRDREVTRCGGLPNNIVDVWEFLGKPKHCQYTWDTQMNSNLGITAACKLRFDRIFFRAAAEEGHIIPRSLDLLGLEKLDCGRFPSDHWGLLCNLDIIL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MELGSCLE -------CCCHHCCC	9.65	22223895
23	Ubiquitination	EEGEPEVKKRRLLCV HCCCCHHCHHEEEEH	38.61	21906983
23	Sumoylation	EEGEPEVKKRRLLCV HCCCCHHCHHEEEEH	38.61	28112733
24	Ubiquitination	EGEPEVKKRRLLCVE CCCCHHCHHEEEEHH	48.18	-
53 (in isoform 2)	Ubiquitination	-	33.75	-
54 (in isoform 2)	Ubiquitination	-	3.53	-
60	Phosphorylation	EMERALNSYFEPPVE HHHHHHHHHCCCCCC	31.86	28796482
61	Phosphorylation	MERALNSYFEPPVEE HHHHHHHHCCCCCCH	15.76	28796482
69	Phosphorylation	FEPPVEESALERRPE CCCCCCHHHHHHCCC	25.34	28555341
82	Ubiquitination	PETISEPKTYVDLTN CCCCCCCCCEEECCC	48.73	21890473
82 (in isoform 1)	Ubiquitination	-	48.73	21890473
82	Sumoylation	PETISEPKTYVDLTN CCCCCCCCCEEECCC	48.73	28112733
83	Phosphorylation	ETISEPKTYVDLTNE CCCCCCCCEEECCCC	39.22	28796482
84	Phosphorylation	TISEPKTYVDLTNEE CCCCCCCEEECCCCC	9.70	28796482
88	Phosphorylation	PKTYVDLTNEETTDS CCCEEECCCCCCCCC	35.80	28450419
92	Phosphorylation	VDLTNEETTDSTTSK EECCCCCCCCCCCCC	29.71	25159151
93	Phosphorylation	DLTNEETTDSTTSKI ECCCCCCCCCCCCCC	31.09	28450419
95	Phosphorylation	TNEETTDSTTSKISP CCCCCCCCCCCCCCC	31.34	25159151
96	Phosphorylation	NEETTDSTTSKISPS CCCCCCCCCCCCCCC	37.59	25262027
97	Phosphorylation	EETTDSTTSKISPSE CCCCCCCCCCCCCCC	31.79	25262027
98	Phosphorylation	ETTDSTTSKISPSED CCCCCCCCCCCCCCC	28.25	25627689
112 (in isoform 2)	Ubiquitination	-	28.39	21890473
114 (in isoform 2)	Phosphorylation	-	6.02	27642862
125 (in isoform 3)	Ubiquitination	-	53.53	21890473
125 (in isoform 2)	Phosphorylation	-	53.53	27642862
139	Phosphorylation	RARGVCSYLALYSPD HHHHHHHHHHHHCCC	7.29	22817900
157	Phosphorylation	LQEVIPPYYSYLKKR EEECCHHHHHHHHHH	10.33	22817900
158	Phosphorylation	QEVIPPYYSYLKKRS EECCHHHHHHHHHHC	9.16	22817900
160	Phosphorylation	VIPPYYSYLKKRSSN CCHHHHHHHHHHCCC	13.35	22817900
190	Ubiquitination	MLKKSRVKLKSQEII EEECCCCCCCCCCCC	49.43	-
192	Sumoylation	KKSRVKLKSQEIIPF ECCCCCCCCCCCCCC	44.36	-
192	Ubiquitination	KKSRVKLKSQEIIPF ECCCCCCCCCCCCCC	44.36	21906983
192	Sumoylation	KKSRVKLKSQEIIPF ECCCCCCCCCCCCCC	44.36	-
203	Sumoylation	IIPFPSTKMMRNLLC CCCCCCCHHHHCEEE	34.73	-
203	Sumoylation	IIPFPSTKMMRNLLC CCCCCCCHHHHCEEE	34.73	-
203 (in isoform 1)	Ubiquitination	-	34.73	21890473
203	Ubiquitination	IIPFPSTKMMRNLLC CCCCCCCHHHHCEEE	34.73	21890473
203	Acetylation	IIPFPSTKMMRNLLC CCCCCCCHHHHCEEE	34.73	25953088
220 (in isoform 2)	Ubiquitination	-	2.93	-
222 (in isoform 2)	Ubiquitination	-	7.02	-
233 (in isoform 2)	Ubiquitination	-	20.62	21890473
242	Ubiquitination	AERMNQLKMVLKKMQ HHHHHHHHHHHHHHH	19.73	-
242	Acetylation	AERMNQLKMVLKKMQ HHHHHHHHHHHHHHH	19.73	25953088
247	Ubiquitination	QLKMVLKKMQEAPES HHHHHHHHHHHCCCC	41.47	21906983
254	Phosphorylation	KMQEAPESATVIFAG HHHHCCCCCEEEEEC	28.34	-
272 (in isoform 2)	Ubiquitination	-	23.43	-
277 (in isoform 2)	Ubiquitination	-	34.79	-
289	Ubiquitination	DVWEFLGKPKHCQYT HHHHHHCCCCCCEEE	53.71	-
291	Ubiquitination	WEFLGKPKHCQYTWD HHHHCCCCCCEEEEC	61.57	-
319 (in isoform 2)	Ubiquitination	-	3.36	-
321 (in isoform 2)	Ubiquitination	-	16.74	-
341	Ubiquitination	LDLLGLEKLDCGRFP CCCCCCCCCCCCCCC	55.45	2063986
371 (in isoform 2)	Ubiquitination	-		-

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
60	S	Phosphorylation	Kinase	MAPK6	Q16659	GPS
88	T	Phosphorylation	Kinase	ALK4	P36896	PSP
88	T	Phosphorylation	Kinase	ACVR1B	Q61271	GPS
92	T	Phosphorylation	Kinase	ALK4	P36896	PSP
92	T	Phosphorylation	Kinase	ACVR1B	Q61271	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of TYDP2_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of TYDP2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ETS1_HUMAN	ETS1	physical	12743594
PARK7_HUMAN	PARK7	physical	19023331

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.

Related Literatures of Post-Translational Modification

Acetylation

"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
PubMed: 19413330

Phosphorylation

"Ttrap is an essential modulator of Smad3-dependent Nodal signalingduring zebrafish gastrulation and left-right axis determination.";
Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D.,Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D.,Huylebroeck D.;
Development 134:4381-4393(2007).
Cited for: INTERACTION WITH ACVR1B AND SMAD3, PHOSPHORYLATION AT THR-88 ANDTHR-92, AND MUTAGENESIS OF THR-88 AND THR-92.
PubMed: 18039968