CLC9_ANOGA
ID CLC9_ANOGA Reviewed; 356 AA.
AC A0A1S4GMJ4; Q7PJH3;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=CLIP domain-containing serine protease C9 {ECO:0000303|PubMed:33045027};
DE EC=3.4.21.- {ECO:0000255|PROSITE-ProRule:PRU00274};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease C9 subunit p12 {ECO:0000303|PubMed:33045027};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease C9 subunit p30 {ECO:0000303|PubMed:33045027};
DE Flags: Precursor;
GN Name=CLIPC9 {ECO:0000303|PubMed:33045027};
GN ORFNames=AGAP004719 {ECO:0000305};
OS Anopheles gambiae (African malaria mosquito).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Anophelinae; Anopheles.
OX NCBI_TaxID=7165 {ECO:0000312|Proteomes:UP000007062};
RN [1] {ECO:0000312|Proteomes:UP000007062}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=PEST {ECO:0000312|Proteomes:UP000007062};
RX PubMed=12364791; DOI=10.1126/science.1076181;
RA Holt R.A., Subramanian G.M., Halpern A., Sutton G.G., Charlab R.,
RA Nusskern D.R., Wincker P., Clark A.G., Ribeiro J.M.C., Wides R.,
RA Salzberg S.L., Loftus B.J., Yandell M.D., Majoros W.H., Rusch D.B., Lai Z.,
RA Kraft C.L., Abril J.F., Anthouard V., Arensburger P., Atkinson P.W.,
RA Baden H., de Berardinis V., Baldwin D., Benes V., Biedler J., Blass C.,
RA Bolanos R., Boscus D., Barnstead M., Cai S., Center A., Chaturverdi K.,
RA Christophides G.K., Chrystal M.A.M., Clamp M., Cravchik A., Curwen V.,
RA Dana A., Delcher A., Dew I., Evans C.A., Flanigan M.,
RA Grundschober-Freimoser A., Friedli L., Gu Z., Guan P., Guigo R.,
RA Hillenmeyer M.E., Hladun S.L., Hogan J.R., Hong Y.S., Hoover J.,
RA Jaillon O., Ke Z., Kodira C.D., Kokoza E., Koutsos A., Letunic I.,
RA Levitsky A.A., Liang Y., Lin J.-J., Lobo N.F., Lopez J.R., Malek J.A.,
RA McIntosh T.C., Meister S., Miller J.R., Mobarry C., Mongin E., Murphy S.D.,
RA O'Brochta D.A., Pfannkoch C., Qi R., Regier M.A., Remington K., Shao H.,
RA Sharakhova M.V., Sitter C.D., Shetty J., Smith T.J., Strong R., Sun J.,
RA Thomasova D., Ton L.Q., Topalis P., Tu Z.J., Unger M.F., Walenz B.,
RA Wang A.H., Wang J., Wang M., Wang X., Woodford K.J., Wortman J.R., Wu M.,
RA Yao A., Zdobnov E.M., Zhang H., Zhao Q., Zhao S., Zhu S.C., Zhimulev I.,
RA Coluzzi M., della Torre A., Roth C.W., Louis C., Kalush F., Mural R.J.,
RA Myers E.W., Adams M.D., Smith H.O., Broder S., Gardner M.J., Fraser C.M.,
RA Birney E., Bork P., Brey P.T., Venter J.C., Weissenbach J., Kafatos F.C.,
RA Collins F.H., Hoffman S.L.;
RT "The genome sequence of the malaria mosquito Anopheles gambiae.";
RL Science 298:129-149(2002).
RN [2] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:33045027};
RX PubMed=33045027; DOI=10.1371/journal.ppat.1008985;
RA Sousa G.L., Bishnoi R., Baxter R.H.G., Povelones M.;
RT "The CLIP-domain serine protease CLIPC9 regulates melanization downstream
RT of SPCLIP1, CLIPA8, and CLIPA28 in the malaria vector Anopheles gambiae.";
RL PLoS Pathog. 16:e1008985-e1008985(2020).
CC -!- FUNCTION: Probable serine protease which plays an essential role in the
CC innate immune response against bacteria and protozoa infection by
CC activating the melanization cascade (PubMed:33045027). In the
CC susceptible strain G3, appears to be dispensable for ookinete
CC elimination which occurs by lysis (PubMed:33045027).
CC {ECO:0000269|PubMed:33045027}.
CC -!- SUBUNIT: In the active form, heterodimer of a p12 subunit and a p30
CC subunit; disulfide-linked. {ECO:0000269|PubMed:33045027}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33045027}.
CC Note=Secreted into the hemolymph (PubMed:33045027). Recruited by CLIPA8
CC to microbial surfaces where it is cleaved into the two chain active
CC form (PubMed:33045027). {ECO:0000269|PubMed:33045027}.
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: Secreted as a full-length protein (PubMed:12364791). Following
CC bacterium E.coli infection, proteolytically cleaved into two chains,
CC p12 and p30, which remain covalently linked (PubMed:12364791).
CC {ECO:0000269|PubMed:12364791}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a loss in
CC phenoloxidase (PO) activity and a reduction in microbe melanization in
CC response to E.coli infection (PubMed:33045027). RNAi-mediated knockdown
CC in the susceptible strain G3 infected with P.berghei, does not affect
CC the number of oocysts and ookinete melanization; however, severely
CC reduces ookinete melanization caused by CTL4 RNAi-mediated knockdown
CC (PubMed:33045027). {ECO:0000269|PubMed:33045027}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA43757.3; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AAAB01008968; EAA43757.3; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_318110.3; XM_318110.4.
DR PaxDb; Q7PJH3; -.
DR EnsemblMetazoa; AGAP004719-RA; AGAP004719-PA; AGAP004719.
DR GeneID; 1278509; -.
DR KEGG; aga:AgaP_AGAP004719; -.
DR CTD; 1278509; -.
DR VEuPathDB; VectorBase:AGAP004719; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_0_3_1; -.
DR InParanoid; Q7PJH3; -.
DR OrthoDB; 1314811at2759; -.
DR Proteomes; UP000007062; Chromosome 2L.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0140546; P:defense response to symbiont; IMP:UniProtKB.
DR GO; GO:0035008; P:positive regulation of melanization defense response; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
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; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
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 Disulfide bond; Glycoprotein; Hydrolase; Immunity; Innate immunity;
KW Protease; Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..?
FT /evidence="ECO:0000305"
FT CHAIN ?..108
FT /note="CLIP domain-containing serine protease C9 subunit
FT p12"
FT /evidence="ECO:0000303|PubMed:33045027"
FT /id="PRO_0000455770"
FT CHAIN 109..356
FT /note="CLIP domain-containing serine protease C9 subunit
FT p30"
FT /evidence="ECO:0000303|PubMed:33045027"
FT /id="PRO_0000455771"
FT CHAIN ?..356
FT /note="CLIP domain-containing serine protease C9"
FT /id="PRO_0000455769"
FT DOMAIN 49..94
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 109..351
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 154
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 194
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 304
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT SITE 108..109
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9XXV0"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 50..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 60..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 66..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 139..155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 258..284
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 300..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 356 AA; 39687 MW; 771086AF67CD1832 CRC64;
MCILTLVERK HLKNMVHVRL LVMMHILIIY STFGAVRRPI NIRVLEGNSC DTPQVIGGKC
MNISLCDPAF VHSIAYQEHT PVCQQNAFYR VICCQPFLDF CENSKQFQIM HGIEAEPGMF
PHLARLGLKS EEDGIAWTCS ANIISERFLL TAAHCNPVNI AGLGCAESMQ CDQQNTVKSF
ISNPKYKTSF KYHDIALVEL EQNIRFNKRV LPICPYISKT DLHESEDLVI AGWGATESHF
QSPRLMFATV RTVLQNDCKD HYASLLKASP NKKLHQGITD EMYCAQGALV DNVTEYIDAC
SGDSGGPLQT KQNNNLYLIG VISTGFGCGS SSPGLYTRVA SYFGWIKETV SATRDN
