ID SER7_DROME Reviewed; 391 AA. AC Q9V3Z2; F7VJU2; Q6BD09; Q95SU8; Q9I7L2; DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 02-OCT-2024, entry version 186. DE RecName: Full=Serine protease 7 {ECO:0000303|PubMed:16256951}; DE EC=3.4.21.- {ECO:0000269|PubMed:24260243}; DE AltName: Full=Melanization protease 2 {ECO:0000303|PubMed:16861233}; DE Flags: Precursor; GN Name=Sp7 {ECO:0000312|FlyBase:FBgn0037515}; GN Synonyms=MP2 {ECO:0000303|PubMed:16861233}, GN PAE1 {ECO:0000303|PubMed:16322759}; GN ORFNames=CG3066 {ECO:0000312|FlyBase:FBgn0037515}; 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:AAF43410.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RA Ryu J.H., Lee W.J.; RT "Molecular cloning of a Drosophila serine proteinase homologous to RT easter."; RL Submitted (FEB-2000) 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:AAL25514.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL25514.1}; RC TISSUE=Embryo {ECO:0000312|EMBL:AAL25514.1}; 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:0000312|EMBL:AAT76546.1} RP NUCLEOTIDE SEQUENCE [MRNA] OF 36-359. RX PubMed=15579698; DOI=10.1534/genetics.104.030478; RA Swanson W.J., Wong A., Wolfner M.F., Aquadro C.F.; RT "Evolutionary expressed sequence tag analysis of Drosophila female RT reproductive tracts identifies genes subjected to positive selection."; RL Genetics 168:1457-1465(2004). RN [6] {ECO:0000312|EMBL:AEH59645.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 151-391. RC TISSUE=Embryo {ECO:0000312|EMBL:AEH59645.1}; RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.; RL Submitted (JUN-2011) to the EMBL/GenBank/DDBJ databases. RN [7] {ECO:0000305} RP FUNCTION, DEVELOPMENTAL STAGE, INDUCTION BY WOUNDING AND BACTERIA, AND RP DISRUPTION PHENOTYPE. RX PubMed=16256951; DOI=10.1016/j.bbrc.2005.10.042; RA Castillejo-Lopez C., Haecker U.; RT "The serine protease Sp7 is expressed in blood cells and regulates the RT melanization reaction in Drosophila."; RL Biochem. Biophys. Res. Commun. 338:1075-1082(2005). RN [8] {ECO:0000305} RP FUNCTION. 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 [9] {ECO:0000305} RP FUNCTION, AND DISRUPTION PHENOTYPE. 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 [10] {ECO:0000305} RP FUNCTION. RX PubMed=18854145; DOI=10.1016/j.devcel.2008.08.017; RA Tang H., Kambris Z., Lemaitre B., Hashimoto C.; RT "A serpin that regulates immune melanization in the respiratory system of RT Drosophila."; RL Dev. Cell 15:617-626(2008). RN [11] {ECO:0000305} RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=19071960; DOI=10.1371/journal.pbio.0060305; RA Ayres J.S., Schneider D.S.; RT "A signaling protease required for melanization in Drosophila affects RT resistance and tolerance of infections."; RL PLoS Biol. 6:2764-2773(2008). RN [12] {ECO:0000305} RP 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 [13] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SPN27A, SUBCELLULAR RP LOCATION, AND CLEAVAGE. 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). CC -!- FUNCTION: Serine protease that, by cleaving and activating CC prophenoloxidase (PPO1) after immune challenge, plays an essential role CC in the melanization immune response to septic wounding CC (PubMed:16256951, PubMed:16322759, PubMed:16861233, PubMed:19071960, CC PubMed:24260243). May function in diverse Hayan-dependent PPO1- CC activating cascades that are negatively controlled by different serpin CC proteins; Spn27A in the hemolymph and Spn77BA in the trachea CC (PubMed:16322759, PubMed:18854145, PubMed:24260243). Important for the CC innate immune response to fungi (PubMed:16861233). Regulation of CC melanization and PPO1 activation appears to be largely independent of CC the Toll signaling pathway (PubMed:16861233). CC {ECO:0000269|PubMed:16256951, ECO:0000269|PubMed:16322759, CC ECO:0000269|PubMed:16861233, ECO:0000269|PubMed:18854145, CC ECO:0000269|PubMed:19071960, ECO:0000269|PubMed:24260243}. CC -!- SUBUNIT: Interacts with Spn27A. {ECO:0000269|PubMed:24260243}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24260243}. CC -!- DEVELOPMENTAL STAGE: First detected in stage 11 embryos, in cells close CC to the gnathal region. At stage 13, expressed in numerous cells that CC are dispersed throughout the embryo. During organogenesis predominantly CC expressed under the cuticle in the proventricular zone close to the CC hindgut. In L3 larvae, expressed in the lymph glands, the hematopoietic CC organ that flanks the dorsal vessel and in mature hemolymph crystal CC cells that appear in clusters attached to diverse organs. CC {ECO:0000269|PubMed:16256951}. CC -!- INDUCTION: Up-regulated after wounding. Levels are higher with septic CC wounding, using either Gram-negative or Gram-positive bacteria. CC {ECO:0000269|PubMed:16256951}. CC -!- DOMAIN: The clip domain consists of 35-55 residues which are 'knitted' CC together usually by 3 conserved disulfide bonds forming a clip-like CC compact structure. {ECO:0000255|PROSITE-ProRule:PRU01236}. CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is semi-pupal lethal, CC with 50% of pupae dying at the late pupal stage or during eclosion CC (PubMed:16861233). Adults display impaired melanization at the site of CC septic infection (septic injury) using either Gram-negative or Gram- CC positive bacteria (PubMed:16256951, PubMed:16861233, PubMed:19071960). CC Reduced survival, PPO1 activity and induction of the antimicrobial CC peptide Drs following septic injury using the fungus B.bassiana CC (PubMed:16256951, PubMed:16861233). Septic injury with various bacteria CC reduces survival (L.monocytogenes, S.typhimurium and S.aureus) and in CC some cases decreases (E.faecelis) or increases bacterial growth CC (L.monocytogenes, S.typhimurium and B.cepacia). Aseptic injury reduces CC survival (PubMed:19071960). Aseptic wounding has no effect on survival CC (PubMed:22227521). Significant increase in survival after immune CC challenge with S.pneumoniae although there is no increase in CC melanization (PubMed:19071960). No effect on the survival following CC infection with various bacteria (E.coli, B.cepacia and E.faecelis) CC (PubMed:19071960). No induction of the antimicrobial peptides Drs and CC Dpt following infection with E.carotovora (PubMed:16861233). CC {ECO:0000269|PubMed:16256951, ECO:0000269|PubMed:16861233, CC ECO:0000269|PubMed:19071960, ECO:0000269|PubMed:22227521}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU01236}. CC -!- SEQUENCE CAUTION: CC Sequence=AAL25514.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF233093; AAF43410.1; -; mRNA. DR EMBL; AE014297; AAF54143.1; -; Genomic_DNA. DR EMBL; AE014297; AAG22126.1; -; Genomic_DNA. DR EMBL; AE014297; AAG22127.2; -; Genomic_DNA. DR EMBL; AY060475; AAL25514.1; ALT_FRAME; mRNA. DR EMBL; AY665379; AAT76546.1; -; mRNA. DR EMBL; BT128742; AEH59645.1; -; mRNA. DR RefSeq; NP_649734.2; NM_141477.2. DR RefSeq; NP_731174.1; NM_169192.3. DR RefSeq; NP_731175.2; NM_169193.3. DR AlphaFoldDB; Q9V3Z2; -. DR SMR; Q9V3Z2; -. DR IntAct; Q9V3Z2; 1. DR STRING; 7227.FBpp0308322; -. DR MEROPS; S01.203; -. DR GlyCosmos; Q9V3Z2; 1 site, No reported glycans. DR PaxDb; 7227-FBpp0081237; -. DR DNASU; 40918; -. DR EnsemblMetazoa; FBtr0081740; FBpp0081237; FBgn0037515. DR EnsemblMetazoa; FBtr0339180; FBpp0308321; FBgn0037515. DR EnsemblMetazoa; FBtr0339181; FBpp0308322; FBgn0037515. DR GeneID; 40918; -. DR KEGG; dme:Dmel_CG3066; -. DR UCSC; CG3066-RA; d. melanogaster. DR UCSC; CG3066-RB; d. melanogaster. DR AGR; FB:FBgn0037515; -. DR CTD; 121340; -. DR FlyBase; FBgn0037515; Sp7. DR VEuPathDB; VectorBase:FBgn0037515; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00940000171279; -. DR HOGENOM; CLU_006842_0_3_1; -. DR InParanoid; Q9V3Z2; -. DR OMA; MRRAYDQ; -. DR OrthoDB; 3680196at2759; -. DR PhylomeDB; Q9V3Z2; -. DR BioGRID-ORCS; 40918; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 40918; -. DR PRO; PR:Q9V3Z2; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0037515; Expressed in second segment of antenna (Drosophila) and 22 other cell types or tissues. DR ExpressionAtlas; Q9V3Z2; baseline and differential. DR GO; GO:0005576; C:extracellular region; HDA:FlyBase. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004252; F:serine-type endopeptidase activity; ISM:FlyBase. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:FlyBase. DR GO; GO:0035006; P:melanization defense response; IMP:FlyBase. DR GO; GO:0035008; P:positive regulation of melanization defense response; IMP:FlyBase. DR GO; GO:0006508; P:proteolysis; ISM:FlyBase. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 3.30.1640.30; -; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR022700; CLIP. DR InterPro; IPR051333; CLIP_Serine_Protease. DR InterPro; IPR038565; CLIP_sf. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24260; -; 1. DR PANTHER; PTHR24260:SF131; CLIP DOMAIN-CONTAINING SERINE PROTEASE-RELATED; 1. DR Pfam; PF12032; CLIP; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00680; CLIP; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS51888; CLIP; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW Calcium; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding; Protease; KW Reference proteome; Secreted; Serine protease; Signal; Zymogen. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT PROPEP 28..136 FT /note="Activation peptide" FT /evidence="ECO:0000305|PubMed:24260243" FT /id="PRO_0000438113" FT CHAIN 137..391 FT /note="Serine protease 7" FT /evidence="ECO:0000305|PubMed:24260243" FT /id="PRO_5007718041" FT DOMAIN 30..84 FT /note="Clip" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236" FT DOMAIN 137..390 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT REGION 91..121 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 91..115 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 182 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 244 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 341 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT BINDING 202 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:O97366" FT BINDING 204 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:O97366" FT BINDING 207 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:O97366" FT BINDING 210 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:O97366" FT CARBOHYD 141 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 31..83 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236" FT DISULFID 41..72 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236" FT DISULFID 47..84 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236" FT DISULFID 128..264 FT /evidence="ECO:0000250|UniProtKB:Q9VB68" FT DISULFID 167..183 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 211..216 FT /evidence="ECO:0000250|UniProtKB:Q9VB68" FT DISULFID 310..327 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 337..366 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" SQ SEQUENCE 391 AA; 43128 MW; 3E1416F12EDF89F6 CRC64; MKSTRKVVGI FLATCLLPFT VLQNVAAQGS CRNPNQKQGQ CLSIYDCQSL LSVIQQSYVS PEDRTFLRNS QCLDGVGRQP YVCCTSDRSF GSQEATSAAP PPTTTSSSSR GQDGQAGLGN LLPSPPKCGP HSFSNKVYNG NDTAIDEFNW MALLEYVDNR GRRELSCGGS LINNRYVLTA AHCVIGAVET EVGHLTTVRL GEYDTSKDVD CIDDICNQPI LQLGIEQATV HPQYDPANKN RIHDIALLRL DRPVVLNEYI QPVCLPLVST RMAINTGELL VVSGWGRTTT ARKSTIKQRL DLPVNDHDYC ARKFATRNIH LISSQLCVGG EFYRDSCDGD SGGPLMRRGF DQAWYQEGVV SFGNRCGLEG WPGVYTRVAD YMDWIVETIR P //