SP28D_DROME
ID SP28D_DROME Reviewed; 536 AA.
AC Q9VLU4;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Serine protease inhibitor 28Dc {ECO:0000303|PubMed:18801354};
DE Short=Serpin 28Dc {ECO:0000312|FlyBase:FBgn0031973};
DE AltName: Full=Serpin-28D {ECO:0000303|PubMed:18801354};
DE Flags: Precursor;
GN Name=Spn28Dc {ECO:0000312|FlyBase:FBgn0031973};
GN Synonyms=Spn28D {ECO:0000312|FlyBase:FBgn0031973};
GN ORFNames=CG7219 {ECO:0000312|FlyBase:FBgn0031973};
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|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 [2] {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 [3] {ECO:0000312|EMBL:ABX00768.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ABX00768.1};
RA Stapleton M., Carlson J., Frise E., Kapadia B., Park S., Wan K., Yu C.,
RA Celniker S.;
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, INDUCTION BY INJURY, 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 [5]
RP FUNCTION.
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).
CC -!- FUNCTION: Serine protease inhibitor which is required for pupal
CC viability and plays an essential role in regulating the melanization
CC reaction (PubMed:18801354, PubMed:22227521). Inhibits spontaneous
CC melanization and appears to be involved in the melanization immune
CC response to physical wounding in larvae and adults (PubMed:18801354,
CC PubMed:22227521). Acts by negatively regulating the Hayan-phenoloxidase
CC (PPO1) cascade in the hemolymph and possibly the trachea
CC (PubMed:18801354, PubMed:22227521). May function by controlling the
CC initial release of the activated form of PPO1, phenoloxidase (PO) and
CC thus maintains PO availability for processes such as wound response and
CC pigmentation (PubMed:18801354). {ECO:0000269|PubMed:18801354,
CC ECO:0000269|PubMed:22227521}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:18801354}.
CC -!- INDUCTION: Up-regulated by injury in larvae and adults.
CC {ECO:0000269|PubMed:18801354}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is often lethal at the
CC pupal stage, with flies displaying small black or brown spots prior to
CC death. A small percentage of adults survive when grown at 23 degrees
CC Celsius to preclude pupal lethality. These adult escapers (then kept at
CC 29 degrees Celsius) do not display melanotic areas until several hours
CC after eclosion. These melanotic regions or spots are predominately in
CC air-exposed parts of the body, such as those close to the cuticle, and
CC the thoracic and abdominal spiracles. In the tracheae melanization
CC occurs only in the trunk closest to the spiracle. The ptilinal suture
CC and the surrounding area between the eyes also display various amounts
CC of melanization. Around half display reduced pigmentation of their
CC abdomen, and this often occurred in adults that had large melanotic
CC areas. After septic injury, flies display impaired melanization at the
CC wound site, and in their hemolymph there is an overall reduction in the
CC protein level of PPO1 and no significant activity of PO.
CC {ECO:0000269|PubMed:18801354}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AE014134; AAF52588.2; -; Genomic_DNA.
DR EMBL; BT031146; ABX00768.1; -; mRNA.
DR RefSeq; NP_609172.1; NM_135328.3.
DR AlphaFoldDB; Q9VLU4; -.
DR SMR; Q9VLU4; -.
DR IntAct; Q9VLU4; 1.
DR STRING; 7227.FBpp0079171; -.
DR MEROPS; I04.084; -.
DR GlyGen; Q9VLU4; 1 site.
DR PaxDb; Q9VLU4; -.
DR DNASU; 34091; -.
DR EnsemblMetazoa; FBtr0079549; FBpp0079171; FBgn0031973.
DR GeneID; 34091; -.
DR KEGG; dme:Dmel_CG7219; -.
DR UCSC; CG7219-RA; d. melanogaster.
DR CTD; 34091; -.
DR FlyBase; FBgn0031973; Spn28Dc.
DR VEuPathDB; VectorBase:FBgn0031973; -.
DR eggNOG; KOG2392; Eukaryota.
DR HOGENOM; CLU_023330_7_1_1; -.
DR InParanoid; Q9VLU4; -.
DR OMA; TMYVIQP; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q9VLU4; -.
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; 34091; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 34091; -.
DR PRO; PR:Q9VLU4; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031973; Expressed in capitellum (Drosophila) and 18 other tissues.
DR ExpressionAtlas; Q9VLU4; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IMP:FlyBase.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
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:0035009; P:negative regulation of melanization defense response; IMP:FlyBase.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP: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; 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.
PE 2: Evidence at transcript level;
KW Developmental protein; Glycoprotein; Immunity; Melanin biosynthesis;
KW Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..536
FT /note="Serine protease inhibitor 28Dc"
FT /evidence="ECO:0000255"
FT /id="PRO_5007718396"
FT SITE 499..500
FT /note="Reactive bond"
FT /evidence="ECO:0000305|PubMed:18801354"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 536 AA; 59350 MW; 3D1240A09CF6101D CRC64;
MWRLLLALLL VSSVCCESEL FRDDLRTPET MAYINGLMQR RHQMQQEAQQ HIQAIPPAVP
LQSPGLVNGL GNQNDPALNR ISGTSVKPSN LPAAYSNGYV DLATSDRIAN SVLNFANILG
QHLANGKTQI YSPLSIVHSL ALLLLGAKGR SYEELSTVFD IPDTSRLHEQ FGLMLQDLQQ
PTREAISAGR PLTDWRASSA MRSNRRAQRP GAHEVHLANG LFTQTGYTLN PDYRRVIVEV
YASDLQIQDF EGSPATARYN INAYVAQHTK NHIENIIASD IPQTTRMILA NALYFKAFWE
TDFIESATRP DNFYPNGEGT EPVMRVQMMA TGGAYPYHED HELGCKIIGL PYRGNLSTMY
IIQPFKSSVR ELMALQKRLT ADKIESMISR MYRRAALVAF PKMHLTESVN LKTVMQRMGL
GGIFSAVQND LSLIATNEAT RTNALGGNSL QNLEAQRRAG TGGARSDLVV DDIVHKVDFT
VNEQGTEAAA SSVTYLKKSG PDVLFRGDTP FMVLVRHDPT KLVLFYGLIN EPPAAA
