SPE_DROME
ID SPE_DROME Reviewed; 400 AA.
AC Q9VCJ8;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Spaetzle-processing enzyme {ECO:0000303|PubMed:16996061};
DE EC=3.4.21.- {ECO:0000269|PubMed:16399077, ECO:0000269|PubMed:26843333};
DE AltName: Full=Spatzle-processing enzyme {ECO:0000303|PubMed:16399077};
DE Contains:
DE RecName: Full=Spaetzle-processing enzyme light chain {ECO:0000305};
DE Contains:
DE RecName: Full=Spaetzle-processing enzyme heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=SPE {ECO:0000312|FlyBase:FBgn0039102};
GN Synonyms=c-SP4 {ECO:0000312|FlyBase:FBgn0039102},
GN SP4 {ECO:0000312|FlyBase:FBgn0039102};
GN ORFNames=CG16705 {ECO:0000312|FlyBase:FBgn0039102};
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:AAK93062.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93062.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAK93062.1};
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 [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16631589; DOI=10.1016/j.cub.2006.03.020;
RA Kambris Z., Brun S., Jang I.H., Nam H.J., Romeo Y., Takahashi K., Lee W.J.,
RA Ueda R., Lemaitre B.;
RT "Drosophila immunity: a large-scale in vivo RNAi screen identifies five
RT serine proteases required for Toll activation.";
RL Curr. Biol. 16:808-813(2006).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, DISRUPTION PHENOTYPE, MUTAGENESIS
RP OF ARG-134, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=16399077; DOI=10.1016/j.devcel.2005.11.013;
RA Jang I.H., Chosa N., Kim S.H., Nam H.J., Lemaitre B., Ochiai M.,
RA Kambris Z., Brun S., Hashimoto C., Ashida M., Brey P.T., Lee W.J.;
RT "A Spatzle-processing enzyme required for toll signaling activation in
RT Drosophila innate immunity.";
RL Dev. Cell 10:45-55(2006).
RN [6] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16996061; DOI=10.1016/j.febslet.2006.09.009;
RA Mulinari S., Haecker U., Castillejo-Lopez C.;
RT "Expression and regulation of Spaetzle-processing enzyme in Drosophila.";
RL FEBS Lett. 580:5406-5410(2006).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=18724373; DOI=10.1038/ni.1643;
RA El Chamy L., Leclerc V., Caldelari I., Reichhart J.M.;
RT "Sensing of 'danger signals' and pathogen-associated molecular patterns
RT defines binary signaling pathways 'upstream' of Toll.";
RL Nat. Immunol. 9:1165-1170(2008).
RN [8] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26843333; DOI=10.1247/csf.16002;
RA Yamamoto-Hino M., Goto S.;
RT "Spaetzle-processing enzyme-independent activation of the toll pathway in
RT Drosophila innate immunity.";
RL Cell Struct. Funct. 41:55-60(2016).
CC -!- FUNCTION: Endopeptidase which plays a key role in innate immunity by
CC cleaving Tl ligand spz and thereby activating the Toll pathway in
CC response to fungal and Gram-positive bacterial infections
CC (PubMed:16631589, PubMed:16399077, PubMed:18724373, PubMed:26843333,
CC PubMed:16996061). Acts downstream of pathogen recognition receptors
CC PGRP-SA and GNBP1 and protease grass in response to Gram-positive
CC bacterial infection (PubMed:16399077). Acts downstream of protease psh
CC in response to fungal infection (PubMed:16399077).
CC {ECO:0000269|PubMed:16399077, ECO:0000269|PubMed:16631589,
CC ECO:0000269|PubMed:16996061, ECO:0000269|PubMed:18724373,
CC ECO:0000269|PubMed:26843333}.
CC -!- SUBUNIT: In the active form, heterodimer of a light chain and a heavy
CC chain; disulfide-linked. {ECO:0000305|PubMed:16399077}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Note=Probably secreted in
CC the hemolymph. {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: In embryogenesis, expressed from stage 11 at the
CC posterior tip of the germ-band; during germline retraction, expressed
CC both ventrally and dorsally; expressed in the developing fat body and
CC lymph nodes. In larvae, expressed in the fat body and in mature
CC hemocytes with weak expression in the lymph glands.
CC {ECO:0000269|PubMed:16996061}.
CC -!- INDUCTION: Up-regulated in response to fungal and Gram-positive
CC bacterial infections. {ECO:0000269|PubMed:16399077,
CC ECO:0000269|PubMed:16996061}.
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 -!- PTM: Proteolytically cleaved in response to Gram-negative bacterial or
CC fungal infection; processing is likely to result in its activation
CC (PubMed:16399077). Cleavage produces a light chain containing the CLIP
CC domain and a catalytic heavy chain which remain covalently associated
CC through an interchain disulfide bond (Probable).
CC {ECO:0000269|PubMed:16399077, ECO:0000305|PubMed:16399077}.
CC -!- DISRUPTION PHENOTYPE: In larvae infected with Gram-positive bacteria,
CC fails to induce the expression of the Toll pathway-activated anti-
CC fungal peptide Drs (PubMed:26843333). siRNA-mediated knockdown results
CC in increased susceptibility to fungal and Gram-positive bacterial
CC infections, failure to cleave spz and to induce the expression of the
CC antifungal peptide Drs (PubMed:16399077, PubMed:16996061). RNAi-
CC mediated knockdown in the fat body causes increased susceptibility to
CC fungal and Gram-positive bacterial infections and failure to induce the
CC expression of the antifungal peptide Drs (PubMed:16631589).
CC {ECO:0000269|PubMed:16399077, ECO:0000269|PubMed:16631589,
CC ECO:0000269|PubMed:16996061, ECO:0000269|PubMed:26843333}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
CC -!- CAUTION: It is not clear if the light chain is degraded after cleavage.
CC {ECO:0000305}.
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DR EMBL; AE014297; AAF56160.2; -; Genomic_DNA.
DR EMBL; AY051638; AAK93062.1; -; mRNA.
DR RefSeq; NP_651168.1; NM_142911.4.
DR AlphaFoldDB; Q9VCJ8; -.
DR SMR; Q9VCJ8; -.
DR STRING; 7227.FBpp0083832; -.
DR MEROPS; S01.462; -.
DR GlyGen; Q9VCJ8; 2 sites.
DR PaxDb; Q9VCJ8; -.
DR PRIDE; Q9VCJ8; -.
DR DNASU; 42791; -.
DR EnsemblMetazoa; FBtr0084440; FBpp0083832; FBgn0039102.
DR GeneID; 42791; -.
DR KEGG; dme:Dmel_CG16705; -.
DR UCSC; CG16705-RA; d. melanogaster.
DR CTD; 42791; -.
DR FlyBase; FBgn0039102; SPE.
DR VEuPathDB; VectorBase:FBgn0039102; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000163739; -.
DR HOGENOM; CLU_006842_0_3_1; -.
DR InParanoid; Q9VCJ8; -.
DR OMA; PSIGTCG; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9VCJ8; -.
DR Reactome; R-DME-209442; Formation of the trans-membrane 'signalling complex'.
DR SignaLink; Q9VCJ8; -.
DR BioGRID-ORCS; 42791; 0 hits in 1 CRISPR screen.
DR ChiTaRS; spen; fly.
DR GenomeRNAi; 42791; -.
DR PRO; PR:Q9VCJ8; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039102; Expressed in capitellum (Drosophila) and 16 other tissues.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017171; F:serine hydrolase activity; HDA:FlyBase.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:FlyBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:FlyBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:FlyBase.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0002804; P:positive regulation of antifungal peptide production; IMP:UniProtKB.
DR GO; GO:0002225; P:positive regulation of antimicrobial peptide production; IMP:FlyBase.
DR GO; GO:0006965; P:positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria; IMP:UniProtKB.
DR GO; GO:0045752; P:positive regulation of Toll signaling pathway; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR GO; GO:0008592; P:regulation of Toll signaling pathway; IMP:UniProtKB.
DR GO; GO:0009620; P:response to fungus; HEP: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; Immunity;
KW Innate immunity; Metal-binding; Protease; Reference proteome; Secreted;
KW Serine protease; Signal; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..134
FT /note="Spaetzle-processing enzyme light chain"
FT /evidence="ECO:0000305|PubMed:16399077"
FT /id="PRO_5010149006"
FT CHAIN 135..400
FT /note="Spaetzle-processing enzyme heavy chain"
FT /evidence="ECO:0000305|PubMed:16399077"
FT /id="PRO_0000443328"
FT DOMAIN 34..94
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 135..399
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 181
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 249
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 346
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 SITE 134..135
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:16399077"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 35..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 46..77
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 52..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 127..269
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 166..182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 211..221
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 315..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 342..375
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MUTAGEN 134
FT /note="R->A: Inhibits zymogen cleavage and thus activation
FT and spz processing."
FT /evidence="ECO:0000269|PubMed:16399077"
SQ SEQUENCE 400 AA; 43947 MW; E4492A4BC7316582 CRC64;
MASTERNFLL LSLVVSALSG LVHRSDAAEI SFGSCTPQQS DERGQCVHIT SCPYLANLLM
VEPKTPAQRI LLSKSQCGLD NRVEGLVNRI LVCCPQSMRG NIMDSEPTPS TRDALQQGDV
LPGNDVCGFL FADRIFGGTN TTLWEFPWMV LLQYKKLFSE TYTFNCGGAL LNSRYVLTAG
HCLASRELDK SGAVLHSVRL GEWDTRTDPD CTTQMNGQRI CAPKHIDIEV EKGIIHEMYA
PNSVDQRNDI ALVRLKRIVS YTDYVRPICL PTDGLVQNNF VDYGMDVAGW GLTENMQPSA
IKLKITVNVW NLTSCQEKYS SFKVKLDDSQ MCAGGQLGVD TCGGDSGGPL MVPISTGGRD
VFYIAGVTSY GTKPCGLKGW PGVYTRTGAF IDWIKQKLEP
