SP27A_DROME
ID SP27A_DROME Reviewed; 447 AA.
AC Q9V3N1;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Serine protease inhibitor 27A {ECO:0000303|PubMed:12408809};
DE Short=Serpin 27A {ECO:0000303|PubMed:12408809};
DE Flags: Precursor;
GN Name=Spn27A {ECO:0000312|FlyBase:FBgn0028990};
GN ORFNames=CG11331 {ECO:0000312|FlyBase:FBgn0028990};
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:AAF24518.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAF24518.1};
RA Page-McCaw A.W., Tsang G., Rubin G.M.;
RT "Drosophila melanogaster serpin 27A.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
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:AAO42650.1, ECO:0000312|EMBL:ADQ54339.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAO42650.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAO42650.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12408809; DOI=10.1016/s1534-5807(02)00267-8;
RA De Gregorio E., Han S.J., Lee W.J., Baek M.J., Osaki T., Kawabata S.,
RA Lee B.L., Iwanaga S., Lemaitre B., Brey P.T.;
RT "An immune-responsive Serpin regulates the melanization cascade in
RT Drosophila.";
RL Dev. Cell 3:581-592(2002).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY BACTERIA, AND MUTAGENESIS OF
RP LYS-406.
RX PubMed=12456640; DOI=10.1093/emboj/cdf661;
RA Ligoxygakis P., Pelte N., Ji C., Leclerc V., Duvic B., Belvin M., Jiang H.,
RA Hoffmann J.A., Reichhart J.M.;
RT "A serpin mutant links Toll activation to melanization in the host defence
RT of Drosophila.";
RL EMBO J. 21:6330-6337(2002).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=14654000; DOI=10.1016/j.cub.2003.10.062;
RA Ligoxygakis P., Roth S., Reichhart J.M.;
RT "A serpin regulates dorsal-ventral axis formation in the Drosophila
RT embryo.";
RL Curr. Biol. 13:2097-2102(2003).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=14667416; DOI=10.1016/s1534-5807(03)00338-1;
RA Hashimoto C., Kim D.R., Weiss L.A., Miller J.W., Morisato D.;
RT "Spatial regulation of developmental signaling by a serpin.";
RL Dev. Cell 5:945-950(2003).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=15749104; DOI=10.1016/j.jinsphys.2004.10.013;
RA Nappi A.J., Frey F., Carton Y.;
RT "Drosophila serpin 27A is a likely target for immune suppression of the
RT blood cell-mediated melanotic encapsulation response.";
RL J. Insect Physiol. 51:197-205(2005).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=16861233; DOI=10.1074/jbc.m601642200;
RA Tang H., Kambris Z., Lemaitre B., Hashimoto C.;
RT "Two proteases defining a melanization cascade in the immune system of
RT Drosophila.";
RL J. Biol. Chem. 281:28097-28104(2006).
RN [11] {ECO:0000305}
RP FUNCTION, AND INDUCTION BY BACTERIA.
RX PubMed=16322759; DOI=10.1038/sj.embor.7400592;
RA Leclerc V., Pelte N., El Chamy L., Martinelli C., Ligoxygakis P.,
RA Hoffmann J.A., Reichhart J.M.;
RT "Prophenoloxidase activation is not required for survival to microbial
RT infections in Drosophila.";
RL EMBO Rep. 7:231-235(2006).
RN [12] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18801354; DOI=10.1016/j.ydbio.2008.08.030;
RA Scherfer C., Tang H., Kambris Z., Lhocine N., Hashimoto C., Lemaitre B.;
RT "Drosophila Serpin-28D regulates hemolymph phenoloxidase activity and adult
RT pigmentation.";
RL Dev. Biol. 323:189-196(2008).
RN [13] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22227521; DOI=10.1038/emboj.2011.476;
RA Nam H.J., Jang I.H., You H., Lee K.A., Lee W.J.;
RT "Genetic evidence of a redox-dependent systemic wound response via Hayan
RT protease-phenoloxidase system in Drosophila.";
RL EMBO J. 31:1253-1265(2012).
RN [14] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH SP7.
RX PubMed=24260243; DOI=10.1371/journal.pone.0079533;
RA An C., Zhang M., Chu Y., Zhao Z.;
RT "Serine protease MP2 activates prophenoloxidase in the melanization immune
RT response of Drosophila melanogaster.";
RL PLoS ONE 8:E79533-E79533(2013).
RN [15] {ECO:0000305}
RP FUNCTION.
RX PubMed=24788090; DOI=10.1371/journal.ppat.1004067;
RA Binggeli O., Neyen C., Poidevin M., Lemaitre B.;
RT "Prophenoloxidase activation is required for survival to microbial
RT infections in Drosophila.";
RL PLoS Pathog. 10:E1004067-E1004067(2014).
CC -!- FUNCTION: Serine protease inhibitor that functions in embryonic
CC dorsoventral patterning and the melanization immune response
CC (PubMed:14654000, PubMed:14667416, PubMed:12408809, PubMed:12456640,
CC PubMed:16861233, PubMed:16322759, PubMed:18801354, PubMed:22227521,
CC PubMed:24260243, PubMed:24788090). Regulates dorsoventral axis
CC formation during early development by inhibiting the serine protease
CC easter, and is therefore important for restricting activity of the Toll
CC signaling pathway to the ventral part of the embryo (PubMed:14654000,
CC PubMed:14667416). Also plays an essential role in the melanization
CC immune response to both physical wounding and septic infection using
CC certain bacteria and fungi (PubMed:12408809, PubMed:12456640,
CC PubMed:18801354, PubMed:22227521). Negatively regulates the Hayan-
CC dependent prophenoloxidase 1 (PPO1)-activating cascade in the hemolymph
CC by inhibiting the serine proteases MP1 and Sp7 (PubMed:12408809,
CC PubMed:12456640, PubMed:16861233, PubMed:16322759, PubMed:18801354,
CC PubMed:22227521, PubMed:24260243, PubMed:24788090). May be involved in
CC negatively regulating the melanotic encapsulation around eggs of the
CC parasite L. boulardi (PubMed:12408809, PubMed:15749104).
CC {ECO:0000269|PubMed:12408809, ECO:0000269|PubMed:12456640,
CC ECO:0000269|PubMed:14654000, ECO:0000269|PubMed:14667416,
CC ECO:0000269|PubMed:15749104, ECO:0000269|PubMed:16322759,
CC ECO:0000269|PubMed:16861233, ECO:0000269|PubMed:18801354,
CC ECO:0000269|PubMed:22227521, ECO:0000269|PubMed:24260243,
CC ECO:0000269|PubMed:24788090}.
CC -!- SUBUNIT: Interacts with Sp7. {ECO:0000269|PubMed:24260243}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12408809,
CC ECO:0000269|PubMed:12456640, ECO:0000269|PubMed:14667416}.
CC Note=Secreted into the hemolymph (PubMed:12456640). Detected in the
CC perivitelline fluid of embryos (PubMed:14667416).
CC {ECO:0000269|PubMed:12456640, ECO:0000269|PubMed:14667416}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all developmental stages, with lowest
CC levels at the adult stage (at protein level) (PubMed:12408809).
CC Uniformly expressed along the dorsoventral axis of embryos (at protein
CC level) (PubMed:14667416). At the periphery of syncytial blastoderm
CC embryos, expression is often weakest at the anterior and posterior
CC termini (at protein level) (PubMed:14667416).
CC {ECO:0000269|PubMed:12408809, ECO:0000269|PubMed:14667416}.
CC -!- INDUCTION: In adults, up-regulated between 0 and 3 hours after
CC bacterial infection and fungal infection (PubMed:12408809). Then
CC appears to be down-regulated in the hemolymph between 3 and 17 hours
CC after bacterial infection (PubMed:12456640, PubMed:16322759).
CC {ECO:0000269|PubMed:12408809, ECO:0000269|PubMed:12456640,
CC ECO:0000269|PubMed:16322759}.
CC -!- DISRUPTION PHENOTYPE: Loss of maternal expression causes arrest prior
CC to the syncytial blastoderm stage (PubMed:14667416). A percentage of
CC larvae and adults, 40% and 35% respectively, display spontaneous
CC melanization (PubMed:12408809). Melanization occurs mainly around the
CC internal organs such as the gut and fat body, but is not associated
CC with the barrier epithelia of the body wall (PubMed:12408809).
CC Increased melanization following wounding coupled with bacterial
CC infection (PubMed:12408809). Phenoloxidase (PO) activity is increased
CC in the hemolymph, both in mutants that display melanization or those
CC that do not (PubMed:12408809). RNAi-mediated knockdown results in
CC spontaneous melanization (PubMed:22227521). After septic injury PPO1 is
CC absent in the hemolymph, whereas its active form PO is present but at a
CC reduced level (PubMed:18801354). {ECO:0000269|PubMed:12408809,
CC ECO:0000269|PubMed:14667416, ECO:0000269|PubMed:18801354,
CC ECO:0000269|PubMed:22227521}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AE014134; AAF52420.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB92679.1; -; Genomic_DNA.
DR EMBL; AF220045; AAF24518.1; -; mRNA.
DR EMBL; BT004486; AAO42650.1; -; mRNA.
DR EMBL; BT125777; ADQ54339.1; -; mRNA.
DR RefSeq; NP_001260143.1; NM_001273214.1.
DR RefSeq; NP_652024.1; NM_143767.3.
DR AlphaFoldDB; Q9V3N1; -.
DR SMR; Q9V3N1; -.
DR IntAct; Q9V3N1; 3.
DR STRING; 7227.FBpp0305543; -.
DR MEROPS; I04.072; -.
DR GlyGen; Q9V3N1; 2 sites.
DR PaxDb; Q9V3N1; -.
DR PRIDE; Q9V3N1; -.
DR DNASU; 45815; -.
DR EnsemblMetazoa; FBtr0079321; FBpp0078950; FBgn0028990.
DR EnsemblMetazoa; FBtr0333351; FBpp0305543; FBgn0028990.
DR GeneID; 45815; -.
DR KEGG; dme:Dmel_CG11331; -.
DR UCSC; CG11331-RA; d. melanogaster.
DR CTD; 45815; -.
DR FlyBase; FBgn0028990; Spn27A.
DR VEuPathDB; VectorBase:FBgn0028990; -.
DR eggNOG; KOG2392; Eukaryota.
DR HOGENOM; CLU_023330_0_1_1; -.
DR InParanoid; Q9V3N1; -.
DR OMA; KSAQWAM; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q9V3N1; -.
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-209442; Formation of the trans-membrane 'signalling complex'.
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; 45815; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 45815; -.
DR PRO; PR:Q9V3N1; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0028990; Expressed in oviduct (Drosophila) and 35 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:FlyBase.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0098595; C:perivitelline space; IDA:FlyBase.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:FlyBase.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:FlyBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:FlyBase.
DR GO; GO:0002213; P:defense response to insect; IMP:FlyBase.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:FlyBase.
DR GO; GO:0035006; P:melanization defense response; IMP:FlyBase.
DR GO; GO:0035011; P:melanotic encapsulation of foreign target; IMP:FlyBase.
DR GO; GO:0140540; P:negative regulation melanotic encapsulation of foreign target; IMP:FlyBase.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:FlyBase.
DR GO; GO:0035009; P:negative regulation of melanization defense response; IMP:FlyBase.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:FlyBase.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; IDA:FlyBase.
DR GO; GO:0009611; P:response to wounding; 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 1: Evidence at protein level;
KW Glycoprotein; Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..447
FT /note="Serine protease inhibitor 27A"
FT /evidence="ECO:0000255"
FT /id="PRO_5007718039"
FT SITE 406..407
FT /note="Reactive bond"
FT /evidence="ECO:0000303|PubMed:12408809"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 406
FT /note="K->A: Fails to inhibit proteolytic activation of
FT phenoloxidase (PO)."
FT /evidence="ECO:0000269|PubMed:12408809"
FT MUTAGEN 406
FT /note="K->R: Decreased inhibition of proteolytic activation
FT of phenoloxidase (PO)."
FT /evidence="ECO:0000269|PubMed:12408809"
SQ SEQUENCE 447 AA; 49795 MW; 99E78A2C9E0411E1 CRC64;
MTKMGGNLAV MLLSLFLSAL ATGNGNSIPT TTTPQGVFET RTDKLPGGAA SVPSGAGIYD
DIDTFVPFRS DSHDPFSWHL LKTVLQNETA DKNVIISPFS VKLVLALLAE AAGAGTQTQV
ELANTQTDIR SQNNVREFYR KTLNSFKKEN QLHETLSVRT KLFTDSFIET QQKFTATLKH
FYDSEVEALD FTNPEAAADA INAWAANITQ GRLQQLVAPD NVRSSVMLLT NLIYFNGLWR
RQFATTFQGS FFRSKDDQSR AEFMEQTDYF YYTTSEKLKA QILRLPYKGK NSLFVLLPYA
LNGIHDLVKN LENDELKSAQ WAMEEVKVKV TLPKFHFDYQ QNLKETLRSL GVREIFEDSA
SLPGLTRGAD VAGKVKVSNI LQKAGINVNE KGTEAYAATV VEIENKFGGS TAIEEFNVNR
PFVFFIEEES TGNILFAGKV HSPTTQN
