SHARK_DROME
ID SHARK_DROME Reviewed; 939 AA.
AC Q24145; Q26299; Q9V7K5;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Tyrosine-protein kinase Shark {ECO:0000303|PubMed:7892198};
DE EC=2.7.10.2;
GN Name=Shark {ECO:0000303|PubMed:7892198, ECO:0000312|FlyBase:FBgn0015295};
GN Synonyms=Tk7 {ECO:0000303|PubMed:1915852};
GN ORFNames=CG18247 {ECO:0000312|FlyBase:FBgn0015295};
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 {ECO:0000312|EMBL:AAF58044.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=7892198; DOI=10.1073/pnas.92.6.1911;
RA Ferrante A.W. Jr., Reinke R., Stanley E.R.;
RT "Shark, a Src homology 2, ankyrin repeat, tyrosine kinase, is expressed on
RT the apical surfaces of ectodermal epithelia.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:1911-1915(1995).
RN [2] {ECO:0000305}
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;
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 793-849.
RX PubMed=1915852; DOI=10.1016/0014-5793(91)81078-m;
RA Shishido E., Emori Y., Saigo K.;
RT "Identification of seven novel protein-tyrosine kinase genes of Drosophila
RT by the polymerase chain reaction.";
RL FEBS Lett. 289:235-238(1991).
RN [6]
RP FUNCTION, INTERACTION WITH DRPR, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP LYS-698.
RX PubMed=18432193; DOI=10.1038/nature06901;
RA Ziegenfuss J.S., Biswas R., Avery M.A., Hong K., Sheehan A.E., Yeung Y.G.,
RA Stanley E.R., Freeman M.R.;
RT "Draper-dependent glial phagocytic activity is mediated by Src and Syk
RT family kinase signalling.";
RL Nature 453:935-939(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26028435; DOI=10.1016/j.cub.2015.04.037;
RA Evans I.R., Rodrigues F.S., Armitage E.L., Wood W.;
RT "Draper/CED-1 mediates an ancient damage response to control inflammatory
RT blood cell migration in vivo.";
RL Curr. Biol. 25:1606-1612(2015).
CC -!- FUNCTION: Following axon injury, required for recruitment of drpr and
CC glial cells to severed axons and for glial clearance of severed axons
CC from the central nervous system (PubMed:18432193). Together with Src42a
CC and drpr, promotes the migration of macrophages to sites of wounding as
CC part of a signaling cascade where Scr42a detects production of hydrogen
CC peroxide at wound sites which triggers phosphorylation of drpr and
CC subsequent recruitment and activation of shark (PubMed:26028435). May
CC be involved in signal transduction on the apical surface of ectodermal
CC epithelial cells, regulating their polarity during invagination
CC (PubMed:7892198). Crumbs (crb) may be the intracellular signal
CC (PubMed:7892198). {ECO:0000269|PubMed:18432193,
CC ECO:0000269|PubMed:26028435, ECO:0000269|PubMed:7892198}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Interacts with drpr; this is required for the recruitment of
CC drpr and glial cells to severed axons and for the phagocytosis of
CC axonal debris by glial cells following axon injury.
CC {ECO:0000269|PubMed:18432193}.
CC -!- INTERACTION:
CC Q24145; Q9W0A0: drpr; NbExp=3; IntAct=EBI-3403861, EBI-107028;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7892198}.
CC Note=Apical expression in cephalic furrow and tracheal cells. Limited
CC to luminal surface and absent from the basal surface.
CC -!- TISSUE SPECIFICITY: Gastrulation embryos show expression in ectodermal
CC cells along the cephalic furrow and ventral midline. Proctodeum,
CC stomodeum and their derived structures (foregut, atrium, pharynx,
CC esophagus and hindgut) continue to show expression from stage 8-9 to
CC late embryos. Other ectodermally derived structures (frontal sac,
CC salivary gland and labium) and developing tracheal system also show
CC expression. {ECO:0000269|PubMed:7892198}.
CC -!- DEVELOPMENTAL STAGE: Embryos only. {ECO:0000269|PubMed:7892198}.
CC -!- DISRUPTION PHENOTYPE: Strong reduction in the number of macrophages
CC recruited to wound sites (PubMed:26028435). RNAi-mediated knockdown in
CC glial cells abolishes a number of events which normally occur following
CC axon injury including drpr localization at severed axons, glial
CC recruitment to severed axons, up-regulation of drpr in glial cells and
CC clearance of axonal debris from the central nervous system
CC (PubMed:18432193). {ECO:0000269|PubMed:18432193,
CC ECO:0000269|PubMed:26028435}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; U37773; AAA79851.1; -; mRNA.
DR EMBL; AE013599; AAF58044.1; -; Genomic_DNA.
DR EMBL; AY051937; AAK93361.1; -; mRNA.
DR EMBL; S55982; AAB19909.1; -; Genomic_DNA.
DR PIR; S18015; S18015.
DR RefSeq; NP_524743.2; NM_080004.4.
DR AlphaFoldDB; Q24145; -.
DR SMR; Q24145; -.
DR BioGRID; 68999; 3.
DR DIP; DIP-59843N; -.
DR IntAct; Q24145; 2.
DR STRING; 7227.FBpp0086382; -.
DR PaxDb; Q24145; -.
DR PRIDE; Q24145; -.
DR EnsemblMetazoa; FBtr0087244; FBpp0086382; FBgn0015295.
DR GeneID; 44353; -.
DR KEGG; dme:Dmel_CG18247; -.
DR CTD; 44353; -.
DR FlyBase; FBgn0015295; Shark.
DR VEuPathDB; VectorBase:FBgn0015295; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000167610; -.
DR HOGENOM; CLU_000288_3_0_1; -.
DR InParanoid; Q24145; -.
DR OMA; RDPDYQN; -.
DR OrthoDB; 796831at2759; -.
DR PhylomeDB; Q24145; -.
DR BRENDA; 2.7.10.2; 1994.
DR BioGRID-ORCS; 44353; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Shark; fly.
DR GenomeRNAi; 44353; -.
DR PRO; PR:Q24145; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0015295; Expressed in cleaving embryo and 31 other tissues.
DR ExpressionAtlas; Q24145; baseline and differential.
DR Genevisible; Q24145; DM.
DR GO; GO:0005938; C:cell cortex; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:FlyBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:FlyBase.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0046843; P:dorsal appendage formation; IMP:FlyBase.
DR GO; GO:0007391; P:dorsal closure; TAS:FlyBase.
DR GO; GO:0007394; P:dorsal closure, elongation of leading edge cells; IMP:FlyBase.
DR GO; GO:0007306; P:eggshell chorion assembly; IMP:FlyBase.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IMP:FlyBase.
DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; IEP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10347; SH2_Nterm_shark_like; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035061; Shark-like_SH2_N.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00248; ANK; 4.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 2.
PE 1: Evidence at protein level;
KW ANK repeat; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; SH2 domain; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..939
FT /note="Tyrosine-protein kinase Shark"
FT /id="PRO_0000088137"
FT DOMAIN 10..106
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191,
FT ECO:0000305"
FT REPEAT 153..185
FT /note="ANK 1"
FT /evidence="ECO:0000305"
FT REPEAT 186..218
FT /note="ANK 2"
FT /evidence="ECO:0000305"
FT REPEAT 220..252
FT /note="ANK 3"
FT /evidence="ECO:0000305"
FT DOMAIN 288..403
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191,
FT ECO:0000305"
FT DOMAIN 662..921
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 410..446
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..494
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 789
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 668..676
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 698
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 927
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255"
FT MUTAGEN 698
FT /note="K->R: Kinase-dead. No effect on interaction with
FT drpr."
FT /evidence="ECO:0000269|PubMed:18432193"
FT CONFLICT 19
FT /note="A -> V (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="S -> R (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="L -> F (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="D -> E (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="S -> T (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="P -> T (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="C -> S (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 505..506
FT /note="GT -> RA (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 597
FT /note="M -> V (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 611
FT /note="A -> P (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="A -> S (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 898
FT /note="A -> P (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
FT CONFLICT 935..939
FT /note="QTVHI -> KRFTFNPVSIFHFFRC (in Ref. 1; AAA79851)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 939 AA; 104273 MW; 37CC2C3DA25D3F52 CRC64;
MSRDSDPMKW YHGNLSREAA DELLKQGYED GTFLVRESST AAGDFVLSLL CQGEVCHYQV
RRHGGEDAFF SIDDKVQTKI LHGLDTLVDY YQQAANGLPT KLTVPLIRDL PPHNTRSHGV
TNLLHRATSK NESKVVFELL KCGYRNFDAK NQDGQTALHL AALHSDEDIL KHLLNAKVQV
NSSDSFGCQP LHYAARSKPA SFIRTLISAQ ANVQGRNIDN GYVPLHEAAK HGNLEAVQEL
LLAEAPPLPR TSSGEFPFDL AKEAGQTAVE EFLLNYKLPP ANTTRDQWYH GTLTREEAVA
ILKKHAKELL AKQPEVDTSG CFLVRYSESP AASGLVLTLL CDQVVKNFRI SQADLYQNGN
KVQSGGSKFL YIDDGPYWPS VEHLIAHFMR FSYGLPVSLK YPVPPQPKPE VPSFATIPRS
NMKPKAASPA TPPTPVSPHS HHQHPHVPAL TITKKKQKEN SSSMFNTLRL TSPKKALFDM
NSLRKNKSKG KRSDSESSVS GSLAGTEQEL QAAAPMLKSL SFSTEFSTFN ADGVTGSGAA
AAGEVYNVPR NNTPIEIDLP PIAQKTEAEV EYFTKSDVAI ERERAGQWIG NGYQPTMDVL
SLLDQQIKAP AVARLNSLGP NASTESEMAS YLHRKCSGTP STPSATEVEA AKLRFFIEPE
KLVLDREIGH GEFGSVHSGW LLRKSGAGEE SRLEVAIKML SDEHSNKQEF LREASVMMRL
EHKCIVRLIG IAKGEMLMMV QELAPLGSML QYILDHGHEI TANAELKVWA SQIACGMHYL
ESQHFVHRDL AARNILLTAR HQAKISDFGM SRSLRPGSTE YQFTQGGRWP IRWYAPESFN
LGIFSHASDV WSFGVTIWEM FSLGAPPYGE ISNVDAIKLV DSGERLPQPN LCPAYIYAVM
QSCWKERPKD RPTFVYLTEF FARDPDYQNL PELVQTVHI
