MODSP_DROME
ID MODSP_DROME Reviewed; 628 AA.
AC Q9VER6; Q6NP02;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Modular serine protease {ECO:0000303|PubMed:19590012};
DE EC=3.4.21.- {ECO:0000269|PubMed:19590012};
DE Contains:
DE RecName: Full=Modular serine protease non-catalytic chain {ECO:0000305|PubMed:19590012};
DE Contains:
DE RecName: Full=Modular serine protease catalytic chain {ECO:0000305|PubMed:19590012};
DE Flags: Precursor;
GN Name=modSP {ECO:0000303|PubMed:19590012, ECO:0000312|FlyBase:FBgn0051217};
GN Synonyms=Ldlr {ECO:0000312|EMBL:AAM50824.1};
GN ORFNames=CG31217 {ECO:0000312|FlyBase:FBgn0051217};
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;
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:AAM50824.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM50824.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM50824.1};
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:0000312|EMBL:AAR82796.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 211-628.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAR82796.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAR82796.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19590012; DOI=10.1073/pnas.0901924106;
RA Buchon N., Poidevin M., Kwon H.M., Guillou A., Sottas V., Lee B.L.,
RA Lemaitre B.;
RT "A single modular serine protease integrates signals from pattern-
RT recognition receptors upstream of the Drosophila Toll pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12442-12447(2009).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24794300; DOI=10.1016/j.cub.2014.03.062;
RA Tan K.L., Vlisidou I., Wood W.;
RT "Ecdysone mediates the development of immunity in the Drosophila embryo.";
RL Curr. Biol. 24:1145-1152(2014).
CC -!- FUNCTION: Serine protease that plays a key role in innate immunity by
CC activating the Toll pathway in response to infection with Gram-positive
CC bacteria and fungi (PubMed:19590012, PubMed:24794300). During Gram-
CC positive infection, acts downstream of PGRP-SA and upstream of Grass
CC and Spz, and therefore appears to function in a pathway that links
CC detection of Gram-positive lysine-type peptidoglycans to Toll
CC activation (PubMed:19590012). Functions in a separate pathway to the
CC psh-mediated activation of the Toll pathway (PubMed:19590012).
CC {ECO:0000269|PubMed:19590012, ECO:0000269|PubMed:24794300}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19590012}.
CC Note=Localizes at the membrane of lipid vesicles. Secreted from the fat
CC body into the hemolymph at the surface of these lipid vesicles.
CC {ECO:0000269|PubMed:19590012}.
CC -!- PTM: May be proteolytically cleaved via an autocatalytic mechanism.
CC {ECO:0000269|PubMed:19590012}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:19590012). Viable
CC but highly susceptible to septic injury with Gram-positive bacteria and
CC fungi (PubMed:19590012, PubMed:24794300). Adults infected with Gram-
CC positive bacteria E.faecalis and L.monocytogenes rapidly succumb to
CC infection (PubMed:19590012), and display reduced expression of the
CC antimicrobial peptide gene Drs in response to septic injury with the
CC Gram-positive bacteria M.luteus and E.faecalis and also after injection
CC with their purified peptidoglycans (PubMed:19590012). Adults infected
CC with C.albicans display a severe reduction in survival after infection,
CC and show reduced expression of Drs in response to septic injury with
CC living C.albicans and after injection with dead C.albicans
CC (PubMed:19590012). Moderate reduction in survival and Drs expression
CC after infection with A.fumigatus spores (PubMed:19590012). Stage 15
CC embryos also display reduced survival and Drs expression after
CC injection with M.luteus and a moderate decrease in survival after
CC injection with proteases from the fungus A.oryzae (PubMed:24794300). No
CC effect on survival after septic injury with the Gram-negative bacteria
CC E.carotovora (PubMed:19590012). In adults, no effect on Drs expression
CC after injection of proteases derived from the fungi A.oryzae and
CC B.subtilis (PubMed:19590012). In embryos, no effect on survival or
CC expression of the antimicrobial peptide DptA after infection with the
CC Gram-negative bacteria Ecc15 (PubMed:24794300).
CC {ECO:0000269|PubMed:19590012, ECO:0000269|PubMed:24794300}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AE014297; AAF55354.2; -; Genomic_DNA.
DR EMBL; AY118964; AAM50824.1; -; mRNA.
DR EMBL; BT011129; AAR82796.1; -; mRNA.
DR RefSeq; NP_536776.2; NM_080515.3.
DR AlphaFoldDB; Q9VER6; -.
DR SMR; Q9VER6; -.
DR IntAct; Q9VER6; 5.
DR STRING; 7227.FBpp0082798; -.
DR MEROPS; S01.508; -.
DR GlyGen; Q9VER6; 4 sites.
DR PaxDb; Q9VER6; -.
DR DNASU; 42032; -.
DR EnsemblMetazoa; FBtr0083353; FBpp0082798; FBgn0051217.
DR GeneID; 42032; -.
DR KEGG; dme:Dmel_CG31217; -.
DR UCSC; CG31217-RA; d. melanogaster.
DR CTD; 42032; -.
DR FlyBase; FBgn0051217; modSP.
DR VEuPathDB; VectorBase:FBgn0051217; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000167619; -.
DR HOGENOM; CLU_027452_1_0_1; -.
DR InParanoid; Q9VER6; -.
DR OMA; NEIKCPS; -.
DR OrthoDB; 267332at2759; -.
DR PhylomeDB; Q9VER6; -.
DR SignaLink; Q9VER6; -.
DR BioGRID-ORCS; 42032; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 42032; -.
DR PRO; PR:Q9VER6; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0051217; Expressed in crop (Drosophila) and 22 other tissues.
DR ExpressionAtlas; Q9VER6; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISM:FlyBase.
DR GO; GO:0050832; P:defense response to fungus; IGI:FlyBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0035008; P:positive regulation of melanization defense response; IGI:FlyBase.
DR GO; GO:0045752; P:positive regulation of Toll signaling pathway; IMP:FlyBase.
DR GO; GO:0006508; P:proteolysis; ISM:FlyBase.
DR GO; GO:0008592; P:regulation of Toll signaling pathway; IMP:UniProtKB.
DR CDD; cd00033; CCP; 2.
DR CDD; cd00112; LDLa; 4.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 4.10.400.10; -; 4.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR Pfam; PF00057; Ldl_recept_a; 3.
DR Pfam; PF00084; Sushi; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00032; CCP; 2.
DR SMART; SM00192; LDLa; 4.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57424; SSF57424; 4.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS01209; LDLRA_1; 3.
DR PROSITE; PS50068; LDLRA_2; 4.
DR PROSITE; PS50923; SUSHI; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Disulfide bond; Glycoprotein; Hydrolase; Immunity;
KW Innate immunity; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Sushi; Zymogen.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..368
FT /note="Modular serine protease non-catalytic chain"
FT /evidence="ECO:0000305|PubMed:19590012"
FT /id="PRO_0000437749"
FT CHAIN 369..628
FT /note="Modular serine protease catalytic chain"
FT /evidence="ECO:0000305|PubMed:19590012"
FT /id="PRO_0000437750"
FT DOMAIN 26..64
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 69..107
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 122..163
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 166..204
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 222..285
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 300..356
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 369..621
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 414
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 472
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 563
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT SITE 368..369
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:19590012"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 621
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 27..39
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 34..52
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 46..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 70..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 77..95
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 89..106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 123..135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 130..149
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 143..162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 167..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 174..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 186..203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 224..270
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 256..283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 302..341
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 326..354
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 399..415
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 628 AA; 69433 MW; CB27ED630785D338 CRC64;
MQLISFLSNP LFFCALLLKF RTIFAACDSS QFECDNGSCI SQYDVCNGEK NCPDGSDETA
LTCVSQRQHC TKPYFQCTYG ACVIGTAGCN GVNECADGSD ETRLRCGNED DIRQHDRRLQ
GNCKENEFKC PSGICLDKSN FLCDGKDDCA DGTGFDESVE LCGHMECPAY SFKCGTGGCI
SGSLSCNGEN DCYDGSDEAP LLCNTTKKVT TPVVTETPLE LLGCPLPLGD ERPILTGDGS
RVLTGPITRG TVRFSCKQGY VLEGEESSYC AKNKWSTSTI PKCVKYCSTA GEFDGYSTKA
LCTHNGQQVE CRKPFHPPGT EVKFVCSTGF KTLSPLPEMR CMKGGYWNRG RQRCEQDCGQ
LATPIKQFSS GGYTINNTVV PWHVGLYVWH NEKDYHFQCG GSLLTPDLVI TAAHCVYDEG
TRLPYSYDTF RVIAAKFYRN YGETTPEEKR RDVRLIEIAP GYKGRTENYY QDLALLTLDE
PFELSHVIRP ICVTFASFAE KESVTDDVQG KFAGWNIENK HELQFVPAVS KSNSVCRRNL
RDIQADKFCI FTQGKSLACQ GDSGGGFTSE LPTNAFSTWN TARHFLFGVI SNAPNADQCA
HSLTVMTNIQ HFEDMILNAM NRSVETRS
