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