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SPY_DROME
ID   SPY_DROME               Reviewed;         589 AA.
AC   O44783; A4V1F3; Q6AWR4; Q9VZP7;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   21-FEB-2001, sequence version 2.
DT   03-AUG-2022, entry version 157.
DE   RecName: Full=Protein sprouty;
DE            Short=Spry;
GN   Name=sty; ORFNames=CG1921;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=Canton-S;
RX   PubMed=9458049; DOI=10.1016/s0092-8674(00)80919-8;
RA   Hacohen N., Kramer S., Sutherland D., Hiromi Y., Krasnow M.A.;
RT   "Sprouty encodes a novel antagonist of FGF signaling that patterns apical
RT   branching of the Drosophila airways.";
RL   Cell 92:253-263(1998).
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=Head;
RA   Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA   Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL   Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   FUNCTION, INTERACTION WITH DRK AND RASGAP1, AND SUBCELLULAR LOCATION.
RX   PubMed=10089881; DOI=10.1016/s0092-8674(00)80576-0;
RA   Casci T., Vinos J., Freeman M.;
RT   "Sprouty, an intracellular inhibitor of Ras signaling.";
RL   Cell 96:655-665(1999).
RN   [6]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=10226010; DOI=10.1242/dev.126.11.2515;
RA   Kramer S., Okabe M., Hacohen N., Krasnow M.A., Hiromi Y.;
RT   "Sprouty: a common antagonist of FGF and EGF signaling pathways in
RT   Drosophila.";
RL   Development 126:2515-2525(1999).
RN   [7]
RP   FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=10457022; DOI=10.1242/dev.126.18.4139;
RA   Reich A., Sapir A., Shilo B.-Z.;
RT   "Sprouty is a general inhibitor of receptor tyrosine kinase signaling.";
RL   Development 126:4139-4147(1999).
CC   -!- FUNCTION: Inhibitor of tracheal branching that restricts branch budding
CC       by antagonizing the BNL-FGF pathway (BNL: branchless, an fgf inducer of
CC       branching). Acts as an antagonist of EGFR-mediated signaling in the eye
CC       (where it is important for cell determination) midline glia,
CC       chordotonal organs, wing and ovarian follicle cells.
CC       {ECO:0000269|PubMed:10089881, ECO:0000269|PubMed:10226010,
CC       ECO:0000269|PubMed:10457022, ECO:0000269|PubMed:9458049}.
CC   -!- SUBUNIT: Interacts with DRK and RasGAP1 proteins of the Ras pathway.
CC       {ECO:0000269|PubMed:10089881}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10089881,
CC       ECO:0000269|PubMed:9458049}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:10089881, ECO:0000269|PubMed:9458049}; Cytoplasmic
CC       side {ECO:0000269|PubMed:10089881, ECO:0000269|PubMed:9458049}.
CC   -!- TISSUE SPECIFICITY: In ovary, expressed from stage 7 of oogenesis in
CC       the posterior follicle cells and during stage 9 when the follicle cells
CC       migrate posteriorly over the oocyte nucleus, expression is seen in the
CC       dorsal and lateral cells and is excluded from the ventral cells. Once
CC       the migration of follicle cells is complete expressed in the dorsal-
CC       anterior corner of the egg chamber. Expressed in the embryonic tracheal
CC       system, developing eye imaginal disk, embryonic chordotonal organ
CC       precursors, midline glia and wing imaginal disk.
CC       {ECO:0000269|PubMed:10226010, ECO:0000269|PubMed:10457022,
CC       ECO:0000269|PubMed:9458049}.
CC   -!- INDUCTION: By the BNL-FGF pathway in the tracheal system and by the egf
CC       receptor pathway in the wing imaginal disk and the follicle cells of
CC       the ovary. {ECO:0000269|PubMed:10457022, ECO:0000269|PubMed:9458049}.
CC   -!- DOMAIN: The Cys-rich domain is responsible for the localization of the
CC       protein to the plasma membrane.
CC   -!- DISRUPTION PHENOTYPE: Pupal lethal. Mutant embryos and larvae show
CC       ectopic tracheal branching. {ECO:0000269|PubMed:9458049}.
CC   -!- SIMILARITY: Belongs to the sprouty family. {ECO:0000305}.
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DR   EMBL; AF039842; AAC04257.1; -; mRNA.
DR   EMBL; AE014296; AAF47772.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN11566.1; -; Genomic_DNA.
DR   EMBL; BT015184; AAT94413.1; -; mRNA.
DR   RefSeq; NP_523902.2; NM_079178.3.
DR   RefSeq; NP_728881.1; NM_168031.2.
DR   AlphaFoldDB; O44783; -.
DR   BioGRID; 63919; 104.
DR   DIP; DIP-17914N; -.
DR   IntAct; O44783; 6.
DR   STRING; 7227.FBpp0073004; -.
DR   PaxDb; O44783; -.
DR   PRIDE; O44783; -.
DR   EnsemblMetazoa; FBtr0073145; FBpp0073004; FBgn0014388.
DR   EnsemblMetazoa; FBtr0073146; FBpp0073005; FBgn0014388.
DR   GeneID; 38424; -.
DR   KEGG; dme:Dmel_CG1921; -.
DR   CTD; 20914; -.
DR   FlyBase; FBgn0014388; sty.
DR   VEuPathDB; VectorBase:FBgn0014388; -.
DR   eggNOG; ENOG502QTG8; Eukaryota.
DR   HOGENOM; CLU_458038_0_0_1; -.
DR   InParanoid; O44783; -.
DR   OMA; DDYQIHH; -.
DR   OrthoDB; 1157681at2759; -.
DR   PhylomeDB; O44783; -.
DR   Reactome; R-DME-1295596; Spry regulation of FGF signaling.
DR   Reactome; R-DME-182971; EGFR downregulation.
DR   SignaLink; O44783; -.
DR   BioGRID-ORCS; 38424; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; sty; fly.
DR   GenomeRNAi; 38424; -.
DR   PRO; PR:O44783; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0014388; Expressed in wing disc and 29 other tissues.
DR   ExpressionAtlas; O44783; baseline and differential.
DR   Genevisible; O44783; DM.
DR   GO; GO:0045177; C:apical part of cell; IDA:FlyBase.
DR   GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:FlyBase.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR   GO; GO:0060446; P:branching involved in open tracheal system development; IMP:UniProtKB.
DR   GO; GO:0001745; P:compound eye morphogenesis; IMP:FlyBase.
DR   GO; GO:0008069; P:dorsal/ventral axis specification, ovarian follicular epithelium; IMP:FlyBase.
DR   GO; GO:0021782; P:glial cell development; IMP:FlyBase.
DR   GO; GO:0035171; P:lamellocyte differentiation; IMP:FlyBase.
DR   GO; GO:0055001; P:muscle cell development; IMP:FlyBase.
DR   GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:FlyBase.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:FlyBase.
DR   GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0110109; P:negative regulation of imaginal disc-derived wing vein specification; IMP:FlyBase.
DR   GO; GO:0043407; P:negative regulation of MAP kinase activity; IBA:GO_Central.
DR   GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; IMP:FlyBase.
DR   GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IBA:GO_Central.
DR   GO; GO:0120177; P:negative regulation of torso signaling pathway; IGI:FlyBase.
DR   GO; GO:0016318; P:ommatidial rotation; IMP:FlyBase.
DR   GO; GO:0007424; P:open tracheal system development; IMP:FlyBase.
DR   GO; GO:0045314; P:regulation of compound eye photoreceptor development; IGI:FlyBase.
DR   InterPro; IPR007875; Sprouty.
DR   Pfam; PF05210; Sprouty; 1.
DR   PROSITE; PS51227; SPR; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Developmental protein; Membrane; Reference proteome.
FT   CHAIN           1..589
FT                   /note="Protein sprouty"
FT                   /id="PRO_0000076897"
FT   DOMAIN          380..499
FT                   /note="SPR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          102..194
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          239..320
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        102..139
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        146..182
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        239..305
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        38
FT                   /note="N -> T (in Ref. 1; AAC04257)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        241
FT                   /note="L -> M (in Ref. 4; AAT94413)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        262
FT                   /note="Q -> QQQ (in Ref. 1; AAC04257)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        312
FT                   /note="P -> L (in Ref. 1; AAC04257)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        345
FT                   /note="M -> R (in Ref. 4; AAT94413)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   589 AA;  62389 MW;  7450E11987B17B20 CRC64;
     MDRRNGGDPL APPRPPKLLP RVHRPRAPEP TLSGVDHNAG ATASALASGA SSAAPVAIHN
     NNSQQQLSIS AAASNNNTIS IIPASPDFDD YQIHHLTFLP QRPSSLSRNS STASSTTATG
     ISVSGSGSVS GSSSSFTRRR PPAPVPLNNS ISNNNNNSIN NNFLSHFQSA EPASNALGQP
     PASPVTLAQP RPESERLTNE YVDTPLQHAT RSQHPAGQQD NGQTTTHHLL LLPQRNQHLH
     LQQHQQHLQQ QQQQQQQQQQ QQHLQHQQNQ QHARLATTTQ ATSVGSDHTD GLLHSHLQNS
     TTKPPASKQP APPRLGMGLG LGLGLGLNQP IITKQPTPAT QKERMHALEE LLQPGGAGGN
     GGPLVMAGDP SLLNPIVCPR CGRCRCEQCQ SPRPLPQTWV CNKTCLCSAE SVIDYASCLC
     CAKALFYHCA RDNDLDCDDG NGTPCVDNPC SCGPYKRTQR WGWLGALSIF LPCLWFYWPM
     RGCMKLCEKC YGRFAGRGCR CQGIGGGGAG SGGGVGSIGS TSSMLPIVPL GVNGSGLGGG
     VSLSGGVTDG GLNQANGKAM DHGCSAARSI LRKGDLTPEK RLLDSSPDY
 
 
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