TYDP1_MOUSE
ID TYDP1_MOUSE Reviewed; 609 AA.
AC Q8BJ37; Q8VE39;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Tyrosyl-DNA phosphodiesterase 1;
DE Short=Tyr-DNA phosphodiesterase 1;
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q9NUW8};
DE AltName: Full=Protein expressed in male leptotene and zygotene spermatocytes 501;
DE Short=MLZ-501;
GN Name=Tdp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Diencephalon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 212-609.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17914460; DOI=10.1038/sj.emboj.7601869;
RA Katyal S., el-Khamisy S.F., Russell H.R., Li Y., Ju L., Caldecott K.W.,
RA McKinnon P.J.;
RT "TDP1 facilitates chromosomal single-strand break repair in neurons and is
RT neuroprotective in vivo.";
RL EMBO J. 26:4720-4731(2007).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17948061; DOI=10.1038/sj.emboj.7601885;
RA Hirano R., Interthal H., Huang C., Nakamura T., Deguchi K., Choi K.,
RA Bhattacharjee M.B., Arimura K., Umehara F., Izumo S., Northrop J.L.,
RA Salih M.A.M., Inoue K., Armstrong D.L., Champoux J.J., Takashima H.,
RA Boerkoel C.F.;
RT "Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1
RT recessive neomorphic mutation?";
RL EMBO J. 26:4732-4743(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119 AND SER-149, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=20339383; DOI=10.1038/jhg.2010.26;
RA Kogo H., Kowa-Sugiyama H., Yamada K., Bolor H., Tsutsumi M., Ohye T.,
RA Inagaki H., Taniguchi M., Toda T., Kurahashi H.;
RT "Screening of genes involved in chromosome segregation during meiosis I:
RT toward the identification of genes responsible for infertility in humans.";
RL J. Hum. Genet. 55:293-299(2010).
CC -!- FUNCTION: DNA repair enzyme that can remove a variety of covalent
CC adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving
CC rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-
CC end complexes between DNA and the topoisomerase I active site tyrosine
CC residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA
CC double-strand breaks due to DNA damage by radiation and free radicals.
CC Acts on blunt-ended double-strand DNA breaks and on single-stranded
CC DNA. Has low 3'exonuclease activity and can remove a single nucleoside
CC from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no
CC exonuclease activity towards DNA or RNA with a 3'phosphate (By
CC similarity). {ECO:0000250|UniProtKB:Q9NUW8,
CC ECO:0000269|PubMed:17914460, ECO:0000269|PubMed:17948061}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9NUW8}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20339383}. Cytoplasm
CC {ECO:0000269|PubMed:17948061}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:17948061,
CC ECO:0000269|PubMed:20339383}.
CC -!- DISRUPTION PHENOTYPE: Mice display an inability to rapidly repair
CC single-strand DNA breaks due to covalent bonds between TOP1 and DNA.
CC They are hypersensitive to camptothecin, topotecan and bleomycin.
CC {ECO:0000269|PubMed:17914460}.
CC -!- SIMILARITY: Belongs to the tyrosyl-DNA phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH19804.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK033868; BAC28500.1; -; mRNA.
DR EMBL; BC019804; AAH19804.1; ALT_INIT; mRNA.
DR CCDS; CCDS26105.2; -.
DR AlphaFoldDB; Q8BJ37; -.
DR SMR; Q8BJ37; -.
DR IntAct; Q8BJ37; 2.
DR MINT; Q8BJ37; -.
DR STRING; 10090.ENSMUSP00000118656; -.
DR ChEMBL; CHEMBL4523381; -.
DR iPTMnet; Q8BJ37; -.
DR PhosphoSitePlus; Q8BJ37; -.
DR EPD; Q8BJ37; -.
DR jPOST; Q8BJ37; -.
DR MaxQB; Q8BJ37; -.
DR PaxDb; Q8BJ37; -.
DR PRIDE; Q8BJ37; -.
DR ProteomicsDB; 297763; -.
DR UCSC; uc007osf.2; mouse.
DR MGI; MGI:1920036; Tdp1.
DR eggNOG; KOG2031; Eukaryota.
DR InParanoid; Q8BJ37; -.
DR BRENDA; 3.1.4.1; 3474.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR ChiTaRS; Tdp1; mouse.
DR PRO; PR:Q8BJ37; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BJ37; protein.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0017005; F:3'-tyrosyl-DNA phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0006302; P:double-strand break repair; ISO:MGI.
DR GO; GO:0000012; P:single strand break repair; IMP:MGI.
DR InterPro; IPR010347; Tdp1.
DR PANTHER; PTHR12415; PTHR12415; 1.
DR Pfam; PF06087; Tyr-DNA_phospho; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA damage; DNA repair; Exonuclease; Hydrolase; Nuclease;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..609
FT /note="Tyrosyl-DNA phosphodiesterase 1"
FT /id="PRO_0000212487"
FT REGION 1..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..404
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT COMPBIAS 14..28
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..81
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..107
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 264
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT ACT_SITE 494
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT BINDING 266
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT BINDING 496
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT SITE 519
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4G056"
FT MOD_RES 148
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 223
FT /note="N -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="T -> A (in Ref. 2; AAH19804)"
FT /evidence="ECO:0000305"
FT CONFLICT 325
FT /note="T -> I (in Ref. 2; AAH19804)"
FT /evidence="ECO:0000305"
FT CONFLICT 550..609
FT /note="GLDTFKVKQKFFSSSCEPTASFPVPYDLPPELYRSKDRPWIWNIPYVKAPDT
FT HGNMWVPS -> VSNIVPARSLTCVVNGTLFSSSWLSVGLAW (in Ref. 1;
FT BAC28500)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 609 AA; 68689 MW; E23C49C9993E1FC9 CRC64;
MSQESSYGKW TISSSDESED EKPKPDKPSA SSHPQAGQGV SKELIYTCSE ARKVAHKRQI
SPVKFNDADS VLPHKKQKSD SPEGLGWCLS SSDDDQQPDV TQQEQPKRVL PQEKKHVSSP
DVTTAQKVVD RSPPASLRPQ RADDEYETSG EGQDIWDMLD KGNPFQFYLT RVSGIKAKYN
SKALHIKDIL SPLFGTLVSS AQFNYCFDVD WLIKQYPPEF RKNPILLVHG DKREAKADLH
AQAKPYANIS LCQAKLDIAF GTHHTKMMLL LYEEGLRVVI HTSNLIREDW HQKTQGIWLS
PLYPRIDQGS HTAGESSTRF KADLTSYLTA YNAPPLQEWI DIIQEHDLSE TNVYLIGSTP
GRFQGSHRDN WGHFRLRKLL QAHAPSTPKG ECWPIVGQFS SIGSLGPDES KWLCSEFKDS
LLALREEGRP PGKSAVPLHL IYPSVENVRT SLEGYPAGGS LPYSIQTAEK QRWLHSYFHK
WSAETSGRSN AMPHIKTYMR PSPDFSKLAW FLVTSANLSK AAWGALEKNG TQLMIRSYEL
GVLFLPSAFG LDTFKVKQKF FSSSCEPTAS FPVPYDLPPE LYRSKDRPWI WNIPYVKAPD
THGNMWVPS
