TDP2
entrez
51567
canonical
uniprot
O95551
canonical
ensembl
ENSG00000111802
resolver
ensp
ENSP00000367440
resolver
genesymbol
TDP2
resolver
genesymbol_syn
EAP2
resolver
genesymbol_syn
TTRAP
resolver
hgnc
HGNC:17768
resolver
uniprot
A0A384MDM5
resolver
uniprot
B4DKL8
resolver
uniprot
B4DQ95
resolver
uniprot
Q2TBE2
resolver
uniprot
Q5JYM0
resolver
uniprot
Q7Z6U5
resolver
uniprot
Q9NUK5
resolver
uniprot
Q9NYY9
resolver
uniprot_entry
A0A384MDM5_HUMAN
resolver
uniprot_entry
TYDP2_HUMAN
resolver
uniprot_sec
B4DKL8
resolver
uniprot_sec
B4DQ95
resolver
uniprot_sec
Q2TBE2
resolver
uniprot_sec
Q5JYM0
resolver
uniprot_sec
Q7Z6U5
resolver
uniprot_sec
Q9NUK5
resolver
uniprot_sec
Q9NYY9
resolver
amino_acid_sequence
MELGSCLEGGREAAEEEGEPEVKKRRLLCVEFASVASCDAAVAQCFLAENDWEMERALNSYFEPPVEESALERRPETISEPKTYVDLTNEETTDSTTSKISPSEDTQQENGSMFSLITWNIDGLDLNNLSERARGVCSYLALYSPDVIFLQEVIPPYYSYLKKRSSNYEIITGHEEGYFTAIMLKKSRVKLKSQEIIPFPSTKMMRNLLCVHVNVSGNELCLMTSHLESTRGHAAERMNQLKMVLKKMQEAPESATVIFAGDTNLRDREVTRCGGLPNNIVDVWEFLGKPKHCQYTWDTQMNSNLGITAACKLRFDRIFFRAAAEEGHIIPRSLDLLGLEKLDCGRFPSDHWGLLCNLDIIL
uniprot
proteins
disease_involvement
DISEASE: Spinocerebellar ataxia, autosomal recessive, 23 (SCAR23) [MIM:616949]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR23 patients manifest epilepsy, intellectual disability, and gait ataxia. {ECO:0000269|PubMed:24658003}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.4.-
uniprot
proteins
function
FUNCTION: 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 (PubMed:27060144, PubMed:27099339). 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. Also has 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. {ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:21030584, ECO:0000269|PubMed:21921940, ECO:0000269|PubMed:21980489, ECO:0000269|PubMed:22405347, ECO:0000269|PubMed:22822062, ECO:0000269|PubMed:24658003, ECO:0000269|PubMed:27060144, ECO:0000269|PubMed:27099339}.; FUNCTION: (Microbial infection) Used by picornaviruses to remove the small polypeptide, VPg (virus Protein genome-linked, the primer for viral RNA synthesis), from the genomic RNA of the virus. Acts as a 5'-tyrosyl RNA phosphodiesterase and cleaves the covalent VPg-Tyr-RNA bond. This cleavage would play a role in viral replication and occur in viral replication vesicles, but would not act on viral mRNA. {ECO:0000269|PubMed:22908287, ECO:0000269|PubMed:32023921}.
uniprot
proteins
mass_dalton
40930
uniprot
proteins
mutagenesis
MUTAGEN 88; /note="T->A: Abolishes function, but retains ability to interact with SMAD3; when associated with A-92."; /evidence="ECO:0000269|PubMed:18039968"; MUTAGEN 92; /note="T->A: Abolishes function, but retains ability to interact with SMAD3; when associated with A-88."; /evidence="ECO:0000269|PubMed:18039968"; MUTAGEN 120; /note="N->A: Strongly reduced phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:22822062"; MUTAGEN 152; /note="E->A: Loss of phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:22822062"; MUTAGEN 178; /note="Y->F,W: Strongly decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144"; MUTAGEN 206; /note="R->A,K: Loss of phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144"; MUTAGEN 262; /note="D->A: Loss of phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:22822062"; MUTAGEN 262; /note="D->H,L,M: Loss of phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144"; MUTAGEN 305; /note="L->A,F,W: Decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144"; MUTAGEN 316; /note="D->N: Strongly decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144"; MUTAGEN 350; /note="D->N: Strongly decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144"; MUTAGEN 351; /note="H->A: Loss of phosphodiesterase activity. Delayed poliovirus replication in host cells."; /evidence="ECO:0000269|PubMed:22822062, ECO:0000269|PubMed:32023921"; MUTAGEN 351; /note="H->Q: Loss of phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:27060144
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by TRAF6. {ECO:0000269|PubMed:21980489}.
uniprot
proteins
protein_family
CCR4/nocturin family
uniprot
proteins
pubmed
10764746
uniprot
proteins
pubmed
10931946
uniprot
proteins
pubmed
12743594
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14609633
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18039968
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19794497
uniprot
proteins
pubmed
21030584
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21921940
uniprot
proteins
pubmed
21980489
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22405347
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
22822062
uniprot
proteins
pubmed
22908287
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24658003
uniprot
proteins
pubmed
27060144
uniprot
proteins
pubmed
27099339
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
32023921
uniprot
proteins
sequence_length
362
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12743594}. Nucleus, PML body {ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:21921940}. Nucleus, nucleolus {ECO:0000269|PubMed:21921940}. Cytoplasm. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein. {ECO:0000269|PubMed:21921940}.; SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22908287}. Note=(Microbial infection) In case of infection by picornavirus, relocalizes to cytoplasmic sites distinct from those containing viral proteins associated with RNA replication or encapsidation. {ECO:0000269|PubMed:22908287}.
uniprot
proteins