ID SER7_DROME Reviewed; 391 AA. AC Q9V3Z2; F7VJU2; Q6BD09; Q9I7L2; DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 23-MAY-2018, entry version 154. 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; OC Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; 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., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA 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., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA 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., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [3] {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 [4] {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 RT selection."; RL Genetics 168:1457-1465(2004). RN [5] {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 [6] {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 [7] {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 [8] {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 [9] {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 RT of Drosophila."; RL Dev. Cell 15:617-626(2008). RN [10] {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 [11] {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 RT Hayan protease-phenoloxidase system in Drosophila."; RL EMBO J. 31:1253-1265(2012). RN [12] {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 RT immune response of Drosophila melanogaster."; RL PLoS ONE 8:E79533-E79533(2013). CC -!- FUNCTION: Serine protease which, by cleaving and activating CC prophenoloxidase (PPO1) after immune challenge, plays an essential CC role in the melanization immune response to septic wounding CC (PubMed:16256951, PubMed:16322759, PubMed:19071960, CC PubMed:24260243, PubMed:16861233). May function in diverse Hayan- CC dependent PPO1-activating cascades that are negatively controlled CC by different serpin proteins; Spn27A in the hemolymph and Spn77BA CC in the trachea (PubMed:18854145, PubMed:24260243, CC PubMed:16322759). Important for the innate immune response to CC fungi (PubMed:16861233). Regulation of melanization and PPO1 CC activation appears to be largely independent of the Toll signaling CC pathway (PubMed:16861233). {ECO:0000269|PubMed:16256951, CC ECO:0000269|PubMed:16322759, ECO:0000269|PubMed:16861233, CC ECO:0000269|PubMed:18854145, ECO:0000269|PubMed:19071960, CC 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 CC close to the gnathal region. At stage 13, expressed in numerous CC cells that are dispersed throughout the embryo. During CC organogenesis predominantly expressed under the cuticle in the CC proventricular zone close to the hindgut. In L3 larvae, expressed CC in the lymph glands, the hematopoietic organ that flanks the CC dorsal vessel and in mature hemolymph crystal cells that appear in CC clusters attached to diverse organs. CC {ECO:0000269|PubMed:16256951}. CC -!- INDUCTION: Up-regulated after wounding. Levels are higher with CC septic wounding, using either Gram-negative or Gram-positive CC bacteria. {ECO:0000269|PubMed:16256951}. CC -!- DOMAIN: The CLIP domain consists of 37-55 residues which are CC "knitted" together usually by 3 conserved disulfide bonds forming CC a clip-like compact structure. {ECO:0000305}. CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is semi-pupal CC lethal, with 50% of pupae dying at the late pupal stage or during CC eclosion (PubMed:16861233). Adults display impaired melanization CC at the site of septic infection (septic injury) using either Gram- CC negative or Gram-positive bacteria (PubMed:16256951, CC PubMed:16861233, PubMed:19071960). Reduced survival, PPO1 activity CC and induction of the antimicrobial peptide Drs following septic CC injury using the fungus B.bassiana (PubMed:16256951, CC PubMed:16861233). Septic injury with various bacteria reduces CC survival (L.monocytogenes, S.typhimurium and S.aureus) and in some CC cases decreases (E.faecelis) or increases bacterial growth CC (L.monocytogenes, S.typhimurium and B.cepacia). Aseptic injury CC reduces survival (PubMed:19071960). Aseptic wounding has no effect CC on survival (PubMed:22227521). Significant increase in survival CC after immune challenge with S.pneumoniae although there is no CC increase in melanization (PubMed:19071960). No effect on the CC survival following infection with various bacteria (E.coli, CC B.cepacia and E.faecelis) (PubMed:19071960). No induction of the CC antimicrobial peptides Drs and Dpt following infection with CC E.carotovora (PubMed:16861233). {ECO:0000269|PubMed:16256951, CC ECO:0000269|PubMed:16861233, ECO:0000269|PubMed:19071960, CC ECO:0000269|PubMed:22227521}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily. CC {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; AE014297; AAF54143.1; -; Genomic_DNA. DR EMBL; AE014297; AAG22126.1; -; Genomic_DNA. DR EMBL; AE014297; AAG22127.2; -; Genomic_DNA. DR EMBL; AF233093; AAF43410.1; -; 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 UniGene; Dm.6983; -. DR ProteinModelPortal; Q9V3Z2; -. DR SMR; Q9V3Z2; -. DR STRING; 7227.FBpp0081237; -. DR MEROPS; S01.203; -. DR PaxDb; Q9V3Z2; -. DR PRIDE; Q9V3Z2; -. 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 CTD; 121340; -. DR FlyBase; FBgn0037515; Sp7. DR eggNOG; KOG3627; Eukaryota. DR eggNOG; COG5640; LUCA. DR GeneTree; ENSGT00870000136615; -. DR OMA; ISSQLCV; -. DR OrthoDB; EOG091G0DF7; -. DR PhylomeDB; Q9V3Z2; -. DR GenomeRNAi; 40918; -. DR PRO; PR:Q9V3Z2; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0037515; -. DR ExpressionAtlas; Q9V3Z2; differential. DR GO; GO:0005576; C:extracellular region; HDA:FlyBase. 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: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; 2.20.20.90; -; 1. DR InterPro; IPR022700; CLIP. DR InterPro; IPR038565; CLIP_sf. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. 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; SSF50494; 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; Complete proteome; Disulfide bond; Glycoprotein; Hydrolase; KW Metal-binding; Protease; Reference proteome; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1 27 {ECO:0000255}. FT PROPEP 28 136 Activation peptide. FT {ECO:0000305|PubMed:24260243}. FT /FTId=PRO_0000438113. FT CHAIN 137 391 Serine protease 7. FT {ECO:0000305|PubMed:24260243}. FT /FTId=PRO_5007718041. FT DOMAIN 31 84 CLIP. {ECO:0000255}. FT DOMAIN 137 390 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT ACT_SITE 182 182 Charge relay system. FT {ECO:0000255|PROSITE-ProRule:PRU00274}. FT ACT_SITE 244 244 Charge relay system. FT {ECO:0000255|PROSITE-ProRule:PRU00274}. FT ACT_SITE 341 341 Charge relay system. FT {ECO:0000255|PROSITE-ProRule:PRU00274}. FT METAL 202 202 Calcium. {ECO:0000250|UniProtKB:O97366}. FT METAL 204 204 Calcium; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:O97366}. FT METAL 207 207 Calcium; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:O97366}. FT METAL 210 210 Calcium. {ECO:0000250|UniProtKB:O97366}. FT CARBOHYD 141 141 N-linked (GlcNAc...) asparagine. FT {ECO:0000255|PROSITE-ProRule:PRU00498}. FT DISULFID 31 83 {ECO:0000250|UniProtKB:Q9VB68}. FT DISULFID 41 72 {ECO:0000250|UniProtKB:Q9VB68}. FT DISULFID 47 84 {ECO:0000250|UniProtKB:Q9VB68}. FT DISULFID 128 264 {ECO:0000250|UniProtKB:Q9VB68}. FT DISULFID 167 183 {ECO:0000255|PROSITE-ProRule:PRU00274}. FT DISULFID 211 216 {ECO:0000250|UniProtKB:Q9VB68}. FT DISULFID 310 327 {ECO:0000255|PROSITE-ProRule:PRU00274}. FT DISULFID 337 366 {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 //