SER7_DROME
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 03-AUG-2022, entry version 177.
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|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: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 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 of
RT 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 Hayan
RT 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 immune
RT 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 role
CC in the melanization immune response to septic wounding
CC (PubMed:16256951, PubMed:16322759, PubMed:19071960, PubMed:24260243,
CC PubMed:16861233). 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:18854145, PubMed:24260243, PubMed:16322759). 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}.
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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 AlphaFoldDB; Q9V3Z2; -.
DR SMR; Q9V3Z2; -.
DR STRING; 7227.FBpp0081237; -.
DR MEROPS; S01.203; -.
DR GlyGen; Q9V3Z2; 1 site.
DR PaxDb; Q9V3Z2; -.
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 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; HSFSNKV; -.
DR OrthoDB; 1314811at2759; -.
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 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; 2.40.10.10; -; 2.
DR Gene3D; 3.30.1640.30; -; 1.
DR InterPro; IPR022700; CLIP.
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 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; 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
