UniProt Accession

 TYDP2_HUMAN; O95551; B4DKL8; B4DQ95; Q2TBE2; Q5JYM0; Q7Z6U5; Q9NUK5; Q9NYY9 

Genbank Protein ID

 AJ269473; AF201687; AF223469; AK002168; AK296623; AK298699; AY613922; AL031775; AL031775; BC017553; BC110375 

Genbank Nucleotide ID

 CAB92966.1; AAG35600.1; AAF64144.1; BAA92119.1; BAG59230.1; BAG60857.1; AAT09764.1; CAA21141.1; CAD92510.1; AAH17553.1; AAI10376.1 

Protein Name

 Tyrosyl-DNA phosphodiesterase 2 

Protein Synonyms/Alias

 Tyr-DNA phosphodiesterase 2; hTDP2; 5'-tyrosyl-DNA phosphodiesterase; 5'-Tyr-DNA phosphodiesterase; ETS1-associated protein 2; ETS1-associated protein II; EAPII; TRAF and TNF receptor-associated protein; Tyrosyl-RNA phosphodiesterase; VPg unlinkase 

Gene Name

 TDP2 

Gene Synonyms/Alias

 EAP2; TTRAP; AD-022 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
23	EEGEPEVKKRRLLCV	ubiquitination	[1, 2, 3, 4, 5, 6]
24	EGEPEVKKRRLLCVE	ubiquitination	[4]
82	PETISEPKTYVDLTN	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
190	MLKKSRVKLKSQEII	ubiquitination	[4]
192	KKSRVKLKSQEIIPF	ubiquitination	[1, 2, 3, 4, 5, 6, 9]
203	IIPFPSTKMMRNLLC	ubiquitination	[1, 2, 3, 4, 5, 6, 8]
242	AERMNQLKMVLKKMQ	ubiquitination	[4]
247	QLKMVLKKMQEAPES	ubiquitination	[1, 4, 5, 6]
289	DVWEFLGKPKHCQYT	ubiquitination	[2, 4]
291	WEFLGKPKHCQYTWD	ubiquitination	[4]
341	LDLLGLEKLDCGRFP	ubiquitination	[2, 4, 6, 10, 12]

Reference

 [1] 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]
 [2] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [3] 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]
 [4] 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]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [8] 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]
 [9] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [11] 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]
 [12] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865] 

Functional 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. Hydrolyzes 5'- phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. 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 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. Also acts as an adapter by participating to 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. Acts as a regulator of ribosome biogenesis following stress. 

Sequence Annotation

 ACT_SITE 351 351 Proton acceptor (Probable).
 METAL 120 120 Magnesium (Probable).
 METAL 152 152 Magnesium (By similarity).
 METAL 262 262 Magnesium (Probable).
 METAL 264 264 Magnesium (By similarity).
 METAL 350 350 Magnesium (By similarity).
 METAL 351 351 Magnesium (Probable).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 88 88 Phosphothreonine; by ACVR1B.
 MOD_RES 92 92 Phosphothreonine; by ACVR1B.  

Keyword

 Acetylation; Alternative splicing; Complete proteome; Cytoplasm; DNA damage; DNA repair; Hydrolase; Magnesium; Metal-binding; Nuclease; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 362 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0070260; F:5'-tyrosyl-DNA phosphodiesterase activity; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0030145; F:manganese ion binding; IDA:UniProtKB.
 GO:0004518; F:nuclease activity; IEA:UniProtKB-KW.
 GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
 GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
 GO:0036317; F:tyrosyl-RNA phosphodiesterase activity; IDA:UniProtKB.
 GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
 GO:0006302; P:double-strand break repair; IDA:UniProtKB.
 GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IEA:GOC. 

Interpro

 IPR005135; Endo/exonuclease/phosphatase.
 IPR009060; UBA-like. 

Pfam

 PF03372; Exo_endo_phos 

SMART

  

PROSITE

  

PRINTS