CLB14_ANOGA
ID CLB14_ANOGA Reviewed; 375 AA.
AC Q9NAS8; Q7QGN4;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=CLIP domain-containing serine protease B14 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000255|PROSITE-ProRule:PRU00274};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease B14 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease B14 heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=CLIPB14 {ECO:0000303|PubMed:16188883};
GN Synonyms=ser4 {ECO:0000312|EMBL:CAB90819.1};
GN ORFNames=AGAP010833 {ECO:0000312|EMBL:EAA05468.4};
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|EMBL:CAB90819.1};
RN [1] {ECO:0000312|EMBL:CAB90819.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, GLYCOSYLATION, PROTEOLYTIC
RP CLEAVAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16188883; DOI=10.1074/jbc.m506191200;
RA Volz J., Osta M.A., Kafatos F.C., Mueller H.M.;
RT "The roles of two clip domain serine proteases in innate immune responses
RT of the malaria vector Anopheles gambiae.";
RL J. Biol. Chem. 280:40161-40168(2005).
RN [2] {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).
CC -!- FUNCTION: Serine protease (By similarity). Plays a role in innate
CC immunity against infections by parasite P.berghei and by Gram-negative
CC bacteria such as E.coli (PubMed:16188883). In response to P.berghei
CC infection, contributes to the clearing of parasite ookinetes
CC independent of melanization, an innate immune response which consists
CC in the deposition of melanin pigments on invading pathogens and
CC parasites (PubMed:16188883). May play a role in non-septic wound
CC healing (PubMed:16188883). {ECO:0000250|UniProtKB:A0A126GUP6,
CC ECO:0000269|PubMed:16188883}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16188883}.
CC Note=Secreted in the hemolymph. {ECO:0000269|PubMed:16188883}.
CC -!- TISSUE SPECIFICITY: Expressed by a subpopulation of hemocytes.
CC {ECO:0000269|PubMed:16188883}.
CC -!- DEVELOPMENTAL STAGE: Expressed in adult females and to a lesser extent
CC in the second and third larval, and pupal stages.
CC {ECO:0000269|PubMed:16188883}.
CC -!- INDUCTION: Induced by infection with E.coli or S.aureus bacteria.
CC Induced by infection with P.berghei parasite following ookinete
CC invasion of the midgut cells. Induced to some extent upon sterile
CC injury. {ECO:0000269|PubMed:16188883}.
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: N-glycosylated. {ECO:0000269|PubMed:16188883}.
CC -!- PTM: Proteolytically cleaved. {ECO:0000305|PubMed:16188883}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the G3 strain reduces
CC survival following infection by E.coli bacteria but not following
CC infection by S.aureus bacteria. Following P.berghei infection, the
CC number of parasite oocysts in the gut is increased in the susceptible
CC G3 strain due to a failure to kill or/and lyse ookinetes (the motile
CC parasite zygote that enters the gut to form an oocyst). RNAi-mediated
CC knockdown in the refractory L3-5 strain results in an increase in the
CC number of killed and melanized ookinetes following P.berghei infection.
CC Simultaneous knockdown of lectin CTL4 in the G3 strain (but not in L3-5
CC strain) causes an increase in the number of developing oocysts and a
CC decrease in melanized ookinetes. {ECO:0000269|PubMed:16188883}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
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DR EMBL; AJ276487; CAB90819.1; -; mRNA.
DR EMBL; AAAB01008823; EAA05468.4; -; Genomic_DNA.
DR RefSeq; XP_309876.4; XM_309876.4.
DR AlphaFoldDB; Q9NAS8; -.
DR SMR; Q9NAS8; -.
DR STRING; 7165.AGAP010833-PA; -.
DR MEROPS; S01.448; -.
DR PaxDb; Q9NAS8; -.
DR GeneID; 1271130; -.
DR KEGG; aga:AgaP_AGAP010833; -.
DR CTD; 1271130; -.
DR VEuPathDB; VectorBase:AGAP010833; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_0_3_1; -.
DR InParanoid; Q9NAS8; -.
DR OMA; EYTAAGW; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9NAS8; -.
DR Proteomes; UP000007062; Chromosome 3L.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0042832; P:defense response to protozoan; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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 Disulfide bond; Glycoprotein; Hydrolase; Immunity; Innate immunity;
KW Protease; Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..375
FT /note="CLIP domain-containing serine protease B14"
FT /evidence="ECO:0000255"
FT /id="PRO_5013536756"
FT CHAIN 25..100
FT /note="CLIP domain-containing serine protease B14 light
FT chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455750"
FT CHAIN 101..375
FT /note="CLIP domain-containing serine protease B14 heavy
FT chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455751"
FT DOMAIN 29..83
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 101..370
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 146
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 213
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 321
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT SITE 100..101
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 30..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 40..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 46..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 131..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 289..307
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 317..346
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 375 AA; 41117 MW; 3FA9F12C479F40BE CRC64;
MYSRRYVACG LLCLLVIAID QGHGQEHKPC TTPNGTAGRC VRVRECGYVL DLLRKDLFAH
SDTVHLEGLQ CGTRPDGGAL VCCPAFVNEP NCGPSVFGVR IIGGNDTELG EFPWMALLRF
QARNRKIHGN CGASLVSKRF VLSAAHCFTA AKSKGWKIHS VRVAEWNFMN HRGSKDCKQV
KGYDVPICRK DYDVARFVQH PEYRVNAGVH VNDIVLIELA ADVEYNVFVA PICLPVSNDT
AQLPWGSSDD PEIEYTAAGW GSTESGKEST GMSYQLKQIN LRAFNKERCK KLFQVPSGVG
VGLGHICAGG IRDEDTCHGD SGGPLMEAVG GVWYLAGITS FGWPRCGRDG VPGVYTNISH
YMGWLEREMF RGILA
