TYDP1_DROME
ID TYDP1_DROME Reviewed; 580 AA.
AC Q9VQM4; Q95SG3; Q9NFM9;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Probable tyrosyl-DNA phosphodiesterase;
DE Short=Tyr-DNA phosphodiesterase;
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q9NUW8};
DE AltName: Full=Protein glaikit;
GN Name=gkt; Synonyms=Tdp1; ORFNames=CG8825, CG8826;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10940635; DOI=10.1016/s0925-4773(00)00381-6;
RA Dunlop J., Corominas M., Serras F.;
RT "The novel gene glaikit, is expressed during neurogenesis in the Drosophila
RT melanogaster embryo.";
RL Mech. Dev. 96:133-136(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo, and Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15556867; DOI=10.1016/j.cub.2004.10.048;
RA Dunlop J., Morin X., Corominas M., Serras F., Tear G.;
RT "glaikit is essential for the formation of epithelial polarity and neuronal
RT development.";
RL Curr. Biol. 14:2039-2045(2004).
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. May have low 3'exonuclease activity and may be able to remove a
CC single nucleoside from the 3'end of DNA and RNA molecules with
CC 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with
CC a 3'phosphate (By similarity). Required for normal polarization of
CC epidermal cells, correct subcellular location of the Crb complex to the
CC apical lateral membrane, and for normal neuronal development during
CC embryonic development. {ECO:0000250|UniProtKB:Q9NUW8,
CC ECO:0000269|PubMed:15556867}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NUW8}. Cytoplasm
CC {ECO:0000269|PubMed:15556867}.
CC -!- TISSUE SPECIFICITY: Expressed in the delaminating neuroblasts and a few
CC ganglion mother cells in stage 11-14 embryonic central nervous system.
CC Weak expression is seen in gonads at stage 16.
CC {ECO:0000269|PubMed:10940635}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:10940635}.
CC -!- SIMILARITY: Belongs to the tyrosyl-DNA phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL28358.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ277122; CAB86488.1; -; mRNA.
DR EMBL; AE014134; AAF51141.1; -; Genomic_DNA.
DR EMBL; AY051884; AAK93308.1; -; mRNA.
DR EMBL; AY060810; AAL28358.1; ALT_INIT; mRNA.
DR RefSeq; NP_523465.2; NM_078741.4.
DR AlphaFoldDB; Q9VQM4; -.
DR SMR; Q9VQM4; -.
DR BioGRID; 59746; 6.
DR STRING; 7227.FBpp0077263; -.
DR PaxDb; Q9VQM4; -.
DR PRIDE; Q9VQM4; -.
DR DNASU; 33530; -.
DR EnsemblMetazoa; FBtr0077574; FBpp0077263; FBgn0260817.
DR GeneID; 33530; -.
DR KEGG; dme:Dmel_CG8825; -.
DR CTD; 33530; -.
DR FlyBase; FBgn0260817; gkt.
DR VEuPathDB; VectorBase:FBgn0260817; -.
DR eggNOG; KOG2031; Eukaryota.
DR GeneTree; ENSGT00390000002211; -.
DR HOGENOM; CLU_010413_3_0_1; -.
DR InParanoid; Q9VQM4; -.
DR OMA; PLIKECW; -.
DR OrthoDB; 1295967at2759; -.
DR PhylomeDB; Q9VQM4; -.
DR BRENDA; 3.1.4.1; 1994.
DR BioGRID-ORCS; 33530; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33530; -.
DR PRO; PR:Q9VQM4; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0260817; Expressed in procephalic neuroblast (Drosophila) and 19 other tissues.
DR Genevisible; Q9VQM4; DM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0017005; F:3'-tyrosyl-DNA phosphodiesterase activity; IMP:FlyBase.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IMP:FlyBase.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IMP:FlyBase.
DR GO; GO:0000012; P:single strand break repair; IBA:GO_Central.
DR InterPro; IPR019406; APLF_PBZ.
DR InterPro; IPR010347; Tdp1.
DR PANTHER; PTHR12415; PTHR12415; 1.
DR Pfam; PF06087; Tyr-DNA_phospho; 1.
DR Pfam; PF10283; zf-CCHH; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; DNA damage; DNA repair; Exonuclease; Hydrolase; Nuclease;
KW Nucleus; Reference proteome; Repeat.
FT CHAIN 1..580
FT /note="Probable tyrosyl-DNA phosphodiesterase"
FT /id="PRO_0000212489"
FT REGION 65..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..390
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT COMPBIAS 67..117
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 248
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT ACT_SITE 479
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT BINDING 250
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT BINDING 481
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT SITE 504
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT CONFLICT 214
FT /note="L -> V (in Ref. 1; CAB86488)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="G -> R (in Ref. 1; CAB86488)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="L -> R (in Ref. 1; CAB86488)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="A -> P (in Ref. 1; CAB86488)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="L -> P (in Ref. 1; CAB86488)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="K -> N (in Ref. 1; CAB86488)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 580 AA; 64194 MW; 14EC03C1E993BE87 CRC64;
MKECPYGEKC YRKNPIHFGE FSHAHLDAIY AKGNESGDYE IPANYSSEMI HTQLKLLEKL
FPKQATNKEQ EAHSSSSKPA VTAPVASGSS SSGSLDTNPS GSSASGPAAS QDTSNLAKKQ
KLNAKNIRDY IPVVIEKGGM AKKLERAAPY NMFLTAITDS KPTHSEPLSI TLQEILDESL
GEIESTVQIN FMVDIGWLLG HYYFAGILDK PLLLLYGDES PELLSIGKFK QQVTAIRVKM
PTPFATSHTK MMFLGYSDGS MRVVISTANL YEDDWHNRTQ GLWISPKLPA LPVDADTGAG
ESLTGFKQDL MLYLVEYKIS QLQPWIARIR NSDFSAINVF FLGSVPGGHR EGSVRGHPWG
HARLASLLAK HAAPIDDRIP VVCQSSSIGS LGANVQAWIQ QDFVNSLKKD STPVGKLRQM
PPFKMIYPSY GNVAGSHDGM LGGGCLPYGK NTNDKQPWLK DYLQQWKSSD RFRSRAMPHI
KSYTRFNLED QSVYWFVLTS ANLSKAAWGC FNKNSNIQPC LRIANYEAGV LFLPRFVTGE
DTFPLGNNRD GVPAFPLPYD VPLTPYAPDD KPFLMDYLQG
