SP88E_DROME
ID SP88E_DROME Reviewed; 427 AA.
AC Q9VFC2; Q9U1I4;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Serine protease inhibitor 88Ea {ECO:0000303|PubMed:10692585};
DE Short=Serpin 88Ea {ECO:0000312|FlyBase:FBgn0028984};
DE Flags: Precursor;
GN Name=Spn88Ea {ECO:0000312|FlyBase:FBgn0028984};
GN Synonyms=Spn5 {ECO:0000303|PubMed:10692585};
GN ORFNames=CG18525 {ECO:0000312|FlyBase:FBgn0028984};
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|Proteomes:UP000000803};
RN [1] {ECO:0000312|EMBL:CAB63100.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10692585; DOI=10.1016/s0014-5793(00)01224-2;
RA Han J.H., Zhang H., Min G.S., Hashimoto C.;
RT "A novel Drosophila serpin that inhibits serine proteases.";
RL FEBS Lett. 468:194-198(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAM11065.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM11065.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAM11065.1};
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 FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18956323; DOI=10.1387/ijdb.072419yc;
RA Charron Y., Madani R., Combepine C., Gajdosik V., Hwu Y., Margaritondo G.,
RA Vassalli J.D.;
RT "The serpin Spn5 is essential for wing expansion in Drosophila
RT melanogaster.";
RL Int. J. Dev. Biol. 52:933-942(2008).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=19581577; DOI=10.1073/pnas.0903134106;
RA Ahmad S.T., Sweeney S.T., Lee J.A., Sweeney N.T., Gao F.B.;
RT "Genetic screen identifies serpin5 as a regulator of the toll pathway and
RT CHMP2B toxicity associated with frontotemporal dementia.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12168-12173(2009).
CC -!- FUNCTION: Serine protease inhibitor with activity toward trypsin
CC (PubMed:18956323). Negatively regulates the Toll signaling pathway and
CC suppresses the expression of the antifungal peptide drosomycin
CC (PubMed:19581577). Its negative regulation of the Toll signaling
CC pathway also results in the inhibition of the melanization immune
CC response via the phenoloxidase (PPO1) cascade (PubMed:19581577).
CC Essential for unfolding and expansion of the wings after emergence from
CC the pupal case (PubMed:18956323). May regulate the Toll pathway by
CC blocking the proteolysis of the Toll ligand spz (PubMed:19581577).
CC {ECO:0000269|PubMed:18956323, ECO:0000269|PubMed:19581577}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19581577}.
CC -!- TISSUE SPECIFICITY: Expressed in nurse cells and oocytes. Expressed in
CC wings. {ECO:0000269|PubMed:18956323}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed throughout development, with very weak expression between
CC stages 10-16 of embryogenesis and weak expression in adults. In stage
CC 5-6 blastoderm and gastrulating embryos, expression is uniform. In
CC stage 16-17 embryos, expressed in the ventral and dorsal epidermis,
CC posterior spiracles, foregut, hindgut, sensory nervous system
CC primordium, pharynx and respiratory system. In larvae, expressed in the
CC posterior spiracles and tracheal system. In pupae, expressed in the
CC wing imaginal disks. {ECO:0000269|PubMed:18956323}.
CC -!- DISRUPTION PHENOTYPE: Larval lethal (PubMed:19581577). Larvae develop
CC melanotic spots and display an increase in the activity of the
CC activated form of prophenoloxidase 1 (PPO1), phenoloxidase (PO)
CC (PubMed:19581577). Larvae display enhanced activation of the Toll
CC signaling pathway, with increased Tl, spz and Drs expression
CC (PubMed:19581577). RNAi-mediated knockdown of maternal and zygotic
CC expression results in adults that have a reduced lifespan
CC (PubMed:19581577). Wing development appears to be unaffected, however
CC after emergence from the pupal case adult wings fail to unfold and
CC instead remain folded and hypotrophic until death (PubMed:18956323).
CC Other aspects of development in embryos, larvae, pupae and adults
CC appears to be unaffected. {ECO:0000269|PubMed:18956323,
CC ECO:0000269|PubMed:19581577}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AJ251748; CAB63100.1; -; mRNA.
DR EMBL; AE014297; AAF55138.1; -; Genomic_DNA.
DR EMBL; AE014297; AAO41566.1; -; Genomic_DNA.
DR EMBL; AY094712; AAM11065.1; -; mRNA.
DR RefSeq; NP_524954.2; NM_080215.4.
DR RefSeq; NP_788678.1; NM_176501.3.
DR AlphaFoldDB; Q9VFC2; -.
DR SMR; Q9VFC2; -.
DR IntAct; Q9VFC2; 1.
DR STRING; 7227.FBpp0082595; -.
DR MEROPS; I04.085; -.
DR GlyGen; Q9VFC2; 1 site.
DR PaxDb; Q9VFC2; -.
DR PRIDE; Q9VFC2; -.
DR DNASU; 49804; -.
DR EnsemblMetazoa; FBtr0083141; FBpp0082595; FBgn0028984.
DR EnsemblMetazoa; FBtr0083142; FBpp0082596; FBgn0028984.
DR GeneID; 49804; -.
DR KEGG; dme:Dmel_CG18525; -.
DR UCSC; CG18525-RA; d. melanogaster.
DR CTD; 49804; -.
DR FlyBase; FBgn0028984; Spn88Ea.
DR VEuPathDB; VectorBase:FBgn0028984; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000173118; -.
DR HOGENOM; CLU_023330_0_0_1; -.
DR InParanoid; Q9VFC2; -.
DR OMA; MYILLPP; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q9VFC2; -.
DR Reactome; R-DME-114608; Platelet degranulation.
DR Reactome; R-DME-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-DME-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-DME-194002; Glucocorticoid biosynthesis.
DR Reactome; R-DME-204005; COPII-mediated vesicle transport.
DR Reactome; R-DME-3000178; ECM proteoglycans.
DR Reactome; R-DME-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-DME-5694530; Cargo concentration in the ER.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 49804; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 49804; -.
DR PRO; PR:Q9VFC2; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0028984; Expressed in oviduct (Drosophila) and 45 other tissues.
DR GO; GO:0005576; C:extracellular region; HDA:FlyBase.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0048526; P:imaginal disc-derived wing expansion; IMP:FlyBase.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:FlyBase.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:FlyBase.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; IMP:FlyBase.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR InterPro; IPR036186; Serpin_sf.
DR InterPro; IPR042178; Serpin_sf_1.
DR InterPro; IPR042185; Serpin_sf_2.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Immunity; Melanin biosynthesis; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..427
FT /note="Serine protease inhibitor 88Ea"
FT /evidence="ECO:0000269|PubMed:19581577"
FT /id="PRO_5007718228"
FT SITE 386..387
FT /note="Reactive bond"
FT /evidence="ECO:0000250|UniProtKB:Q9VLU4"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CONFLICT 329
FT /note="P -> L (in Ref. 1; CAB63100)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="A -> P (in Ref. 1; CAB63100)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 427 AA; 48476 MW; AEEF32629F5C9D4F CRC64;
MHILSISLMA VLPAIALAGL CGVEPDAGLL DQRLNLYKGQ QNFAVSMLNV IRQSTPNENV
FFSPYSTYHA LLLAYFGSSG DTEKELAKVL HLDWADSKEV VRSAYILEKM NRKERQSKMP
LEFSSADRIF FANDLHVTEC ARNRLAEEVQ QIDFKSQTEE SRKQINDWIA KQTHDQIRNM
LSADEITPRT RLVLANAAYL KGQWLSQFKT EKTVPMPFYT SPSNYSLVSM MQQKGTFLLN
VDEQLRAHVL QLPYRTVFES QEKEDSSPDE NSDISMVLIL PPFNSNSLED VLSRLNADSL
DDSLKQAMPR EIEVSLPKFE FEQRLELNPI LAKMGVSKMF DESVATFDDL TSETISIGDS
KHVAKIKVDE EGSTAAAATV LFTYRSARPV EPAKFECNHP FLFVIYDRTS RSILFTGIYR
DPKTIKQ
