CLA8_ANOGA
ID CLA8_ANOGA Reviewed; 363 AA.
AC A0A1S4H5S2; Q7QDZ6;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Inactive CLIP domain-containing serine protease A8 {ECO:0000305};
DE Contains:
DE RecName: Full=Inactive CLIP domain-containing serine protease A8 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=Inactive CLIP domain-containing serine protease A8 heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=CLIPA8 {ECO:0000303|PubMed:16922859};
GN ORFNames=AGAP010731 {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, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:16922859}, and
RC L3-5 {ECO:0000269|PubMed:16922859};
RX PubMed=16922859; DOI=10.1111/j.1462-5822.2006.00718.x;
RA Volz J., Mueller H.M., Zdanowicz A., Kafatos F.C., Osta M.A.;
RT "A genetic module regulates the melanization response of Anopheles to
RT Plasmodium.";
RL Cell. Microbiol. 8:1392-1405(2006).
RN [3] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INDUCTION, PROTEOLYTIC CLEAVAGE,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:17537726};
RX PubMed=17537726; DOI=10.1074/jbc.m701635200;
RA Schnitger A.K., Kafatos F.C., Osta M.A.;
RT "The melanization reaction is not required for survival of Anopheles
RT gambiae mosquitoes after bacterial infections.";
RL J. Biol. Chem. 282:21884-21888(2007).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:23166497};
RX PubMed=23166497; DOI=10.1371/journal.ppat.1003029;
RA Yassine H., Kamareddine L., Osta M.A.;
RT "The mosquito melanization response is implicated in defense against the
RT entomopathogenic fungus Beauveria bassiana.";
RL PLoS Pathog. 8:e1003029-e1003029(2012).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND 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: Inactive serine protease which plays an essential role in the
CC innate immune response against bacteria, fungi and protozoa infection
CC by activating the melanization cascade (PubMed:16922859,
CC PubMed:17537726, PubMed:23166497, PubMed:33045027). In the melanization
CC cascade, acts downstream of TEP1 and SPCLIP1 to promote CLIPA28 and
CC CLIPC9 proteolytic cleavage and CLIPC9 recruitment to microbial
CC surfaces (PubMed:33045027). In the resistant strain L3-5, required for
CC the melanization of killed parasite P.berghei ookinetes which results
CC in their clearance (PubMed:16922859). In the susceptible strain G3,
CC appears to be dispensable for ookinete elimination which occurs by
CC lysis (PubMed:16922859, PubMed:33045027). Required for the melanization
CC of Gram-positive and Gram-negative bacteria (PubMed:17537726). During
CC the late stage of fungus B.bassiana-mediated infection, required for
CC the initiation of hyphae melanization by promoting prophenoloxidase PPO
CC activation (PubMed:23166497). {ECO:0000269|PubMed:16922859,
CC ECO:0000269|PubMed:17537726, ECO:0000269|PubMed:23166497,
CC ECO:0000269|PubMed:33045027}.
CC -!- SUBUNIT: Heterodimer of a light chain and a heavy chain; disulfide-
CC linked. {ECO:0000269|PubMed:17537726}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17537726,
CC ECO:0000269|PubMed:33045027}. Note=Secreted into the hemolymph.
CC {ECO:0000269|PubMed:17537726, ECO:0000269|PubMed:33045027}.
CC -!- INDUCTION: By Gram-positive and Gram-negative bacteria-mediated
CC infection (PubMed:17537726). By parasite P.berghei infection
CC (PubMed:16922859). {ECO:0000269|PubMed:16922859,
CC ECO:0000269|PubMed:17537726}.
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:0000250|UniProtKB:Q9GRW0}.
CC -!- PTM: Secreted as a full-length protein (PubMed:17537726).
CC Proteolytically cleaved into two chains which remain covalently linked
CC (PubMed:17537726). Cleavage is induced by Gram-positive or Gram-
CC negative bacteria infection (PubMed:17537726).
CC {ECO:0000269|PubMed:17537726}.
CC -!- DISRUPTION PHENOTYPE: In RNAi-mediated knockdown mosquitos infected
CC with bacteria E.coli or S.aureus, bacteria melanization,
CC prophenoloxidase (PPO) activation, and proteolytic cleavage of CLIPA28
CC and CLIPC9 are impaired; however, mosquito survival is not affected
CC (PubMed:17537726, PubMed:33045027). Melanization of wound surfaces is
CC normal (PubMed:17537726). Increased sensitivity to fungus B.bassiana
CC (strain 80.2) infection characterized by reduced mosquito survival and
CC increased levels of hyphal body colonies (PubMed:23166497). Impaired
CC melanization of hyphae, but not of germinating conidia or germ tubes,
CC caused by a failure to recruit prophenoloxidase PPO to hyphae
CC (PubMed:23166497). Loss of phenoloxidase (PO) activity triggered during
CC late but not early fungal infection (PubMed:23166497). RNAi-mediated
CC knockdown in the resistant strain L3-5 infected with P.berghei, results
CC in impaired ookinete melanization without increasing the number of live
CC oocysts (PubMed:16922859). RNAi-mediated knockdown in the susceptible
CC strain G3 infected with P.berghei has no effect on the response to
CC parasite infection (PubMed:16922859, PubMed:33045027). Simultaneous
CC RNAi-mediated knockdown of CLIPA8 and CTL4 in the susceptible strain G3
CC infected with P.berghei, abolishes ookinete melanization caused by
CC RNAi-mediated knockdown of CTL4 (PubMed:16922859, PubMed:33045027).
CC Simultaneous RNAi-mediated knockdown of SRPN2 and CLIPA8, does not
CC rescue the formation of abdominal melanotic tumors caused by SRPN2
CC RNAi-mediated knockdown (PubMed:17537726).
CC {ECO:0000269|PubMed:16922859, ECO:0000269|PubMed:17537726,
CC ECO:0000269|PubMed:23166497, ECO:0000269|PubMed:33045027}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Although it belongs to peptidase S1 family, lacks the
CC conserved Ser residue within the catalytic triad (Asp-His-Ser) which is
CC replaced by a Gly residue, probably resulting in a loss of proteolytic
CC activity. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA07050.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AAAB01008848; EAA07050.2; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_311445.2; XM_311445.2.
DR PaxDb; Q7QDZ6; -.
DR EnsemblMetazoa; AGAP010731-RA; AGAP010731-PA; AGAP010731.
DR GeneID; 1272532; -.
DR KEGG; aga:AgaP_AGAP010731; -.
DR CTD; 1272532; -.
DR VEuPathDB; VectorBase:AGAP010731; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_0_3_1; -.
DR InParanoid; Q7QDZ6; -.
DR OMA; WINATIE; -.
DR OrthoDB; 894557at2759; -.
DR Proteomes; UP000007062; Chromosome 3L.
DR ExpressionAtlas; A0A1S4H5S2; differential.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
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:0010954; P:positive regulation of protein processing; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR041515; PPAF-2_Clip.
DR InterPro; IPR001254; Trypsin_dom.
DR Pfam; PF18322; CLIP_1; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Immunity; Innate immunity;
KW Reference proteome; Secreted; Serine protease homolog; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..363
FT /note="Inactive CLIP domain-containing serine protease A8"
FT /evidence="ECO:0000255"
FT /id="PRO_5013000891"
FT CHAIN 26..66
FT /note="Inactive CLIP domain-containing serine protease A8
FT light chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455763"
FT CHAIN 67..363
FT /note="Inactive CLIP domain-containing serine protease A8
FT heavy chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455764"
FT DOMAIN 33..82
FT /note="Clip"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DOMAIN 114..360
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT SITE 66..67
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 36..80
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 41..73
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 47..81
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 245..317
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 276..297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 307..336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 363 AA; 40130 MW; B787BF80E6FE0BAF CRC64;
MPSWWCCCCL VVLLYAQRMI VPSSAQNDGS DELQECPGGF CSPKYLCPNG TYNEANAQNQ
EIIMLRFGEE DVCQDYMQVC CSNATSMRYE LVTNNEPVEY GCGISNPGGL IYQVEGNRTY
AQYGEFPWVV AILEAFYSSN EQQFTYVGGG TLIHPRFVVT AAHIFNKTEN LVASFGEWDM
NRDENVYPKQ NIDIDRTIIV HPEYNSVGLL NDIALAQLKQ NVVYDKHIRP ICLPNPTDRF
DDQLCISTGW GIEALTSAYA NVLKRVDLPV IARASCKKLF AETRLGPFFR LHKSVLCAGG
EEGADMCDGD GGSGLACPNE SGAYVLAGIV SWGLSCHQQN VPGAYVNVAR FVTWINATIE
GIL
