CLA28_ANOGA
ID CLA28_ANOGA Reviewed; 376 AA.
AC A0A1S4H5M5;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Inactive CLIP domain-containing serine protease A28 {ECO:0000303|PubMed:31765430};
DE Contains:
DE RecName: Full=Inactive CLIP domain-containing serine protease A28 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=Inactive CLIP domain-containing serine protease A28 heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=CLIPA28 {ECO:0000303|PubMed:31765430};
GN ORFNames=AGAP010730 {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, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:31765430};
RX PubMed=31765430; DOI=10.1371/journal.ppat.1008194;
RA El Moussawi L., Nakhleh J., Kamareddine L., Osta M.A.;
RT "The mosquito melanization response requires hierarchical activation of
RT non-catalytic clip domain serine protease homologs.";
RL PLoS Pathog. 15:e1008194-e1008194(2019).
RN [3] {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: 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:31765430,
CC PubMed:33045027). In the melanization cascade, acts downstream of TEP1,
CC SPCLIP1 and CLIPA8 to promote CLIPC9 proteolytic cleavage
CC (PubMed:31765430, PubMed:33045027). In the susceptible strain G3,
CC appears to be dispensable for parasite P.berghei ookinete elimination
CC which occurs by lysis (PubMed:31765430). Required for the melanization
CC of Gram-positive and Gram-negative bacteria (PubMed:31765430,
CC PubMed:33045027). Required for the melanization of fungus B.bassiana
CC (PubMed:31765430). {ECO:0000269|PubMed:31765430,
CC ECO:0000269|PubMed:33045027}.
CC -!- SUBUNIT: May form a heterodimer of a light chain and a heavy chain;
CC disulfide-linked. {ECO:0000269|PubMed:31765430}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31765430,
CC ECO:0000269|PubMed:33045027}. Note=Secreted into the hemolymph.
CC {ECO:0000269|PubMed:31765430, ECO:0000269|PubMed:33045027}.
CC -!- PTM: Secreted as a full-length protein (PubMed:31765430,
CC PubMed:33045027). Proteolytically cleaved into two chains which
CC probably remain covalently linked (PubMed:31765430). Cleavage is
CC induced by fungus B.bassiana and Gram-positive or Gram-negative
CC bacteria infection (PubMed:31765430, PubMed:33045027).
CC {ECO:0000269|PubMed:31765430, ECO:0000269|PubMed:33045027}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a loss in
CC phenoloxidase (PO) activity, a reduction in microbe melanization and
CC CLIPA14 proteolytic cleavage in response to S.aureus infection
CC (PubMed:31765430). Also, causes a reduction in microbe melanization and
CC CLIPC9 proteolytic cleavage in response to E.coli infection
CC (PubMed:33045027). RNAi-mediated knockdown in the susceptible strain G3
CC infected with P.berghei, does not affect the number of oocysts and
CC ookinete melanization; however, severely reduces ookinete melanization
CC caused by CTL4 RNAi-mediated knockdown (PubMed:31765430). Increases
CC susceptibility to fungus B.bassiana-mediated infection but not to
CC P.berghei, E.coli or S.aureus-mediated infection (PubMed:31765430).
CC {ECO:0000269|PubMed:31765430, 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}.
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DR EMBL; AAAB01008848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EnsemblMetazoa; AGAP010730-RA; AGAP010730-PA; AGAP010730.
DR VEuPathDB; VectorBase:AGAP010730; -.
DR Proteomes; UP000007062; Chromosome 3L.
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: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..19
FT /evidence="ECO:0000255"
FT CHAIN 20..376
FT /note="Inactive CLIP domain-containing serine protease A28"
FT /evidence="ECO:0000255"
FT /id="PRO_5012932916"
FT CHAIN 20..60
FT /note="Inactive CLIP domain-containing serine protease A28
FT light chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455765"
FT CHAIN 61..376
FT /note="Inactive CLIP domain-containing serine protease A28
FT heavy chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455766"
FT DOMAIN 24..80
FT /note="Clip"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DOMAIN 114..364
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT SITE 60..61
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 28..78
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 33..71
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 39..79
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 251..321
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 280..301
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 311..340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 376 AA; 41034 MW; 8C674D3503D42396 CRC64;
MKVLLFCIVI SLTTLIASGQ DIEEELRCPG GYCVSKYLCP NGTFIDDIKH AQTTQLIGLR
AGLDIDDFDD CNDYLLVCCQ SAPAPTATST EKPATSDELI EPPPSTNLAC GQANEGGLIY
DLRNNETLSQ YAEYPWVVYI LALKKQEANS GDFVCGGTLI HSRLVVTTAH NTDGKTDLVA
RFGEWDISTT KEPFPQQDID VAEVIKHPQY VFNPIQNDIA LLVLAENVQY AAHIRPICLP
QPTDEFVGQR CVSNGWGKER GVYANVMKKL TLPVIGRANC TRMLRYAGLG PFYTLREGFL
CAGGEVAVDM CKGDGGSPLA CQTESGTYVL AGIVSWGIGC GGFNTPGVYV AVNRYVQWLN
EHIVDQALNE SFDIKL
