CLB4_ANOGA
ID CLB4_ANOGA Reviewed; 360 AA.
AC Q7PEV7; O17489;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=CLIP domain-containing serine protease B4 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000255|PROSITE-ProRule:PRU00274};
DE AltName: Full=CLIP domain-containing serine protease 14D {ECO:0000305};
DE Short=AgSp14D1 {ECO:0000303|PubMed:10469250};
DE Flags: Precursor;
GN Name=CLIPB4 {ECO:0000312|EMBL:EAA45573.1};
GN Synonyms=SP14D1 {ECO:0000303|PubMed:10469250};
GN ORFNames=AGAP003250 {ECO:0000312|EMBL:EAA45573.1};
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|EMBL:AAB62929.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP INDUCTION.
RX PubMed=10469250; DOI=10.1046/j.1365-2583.1999.83124.x;
RA Paskewitz S.M., Reese-Stardy S., Gorman M.J.;
RT "An easter-like serine protease from Anopheles gambiae exhibits changes in
RT transcript abundance following immune challenge.";
RL Insect Mol. Biol. 8:329-337(1999).
RN [2] {ECO:0000312|EMBL:ACN38252.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=GS16359 {ECO:0000312|EMBL:ACN38252.1};
RX PubMed=19234606; DOI=10.1371/journal.pone.0004549;
RA Lehmann T., Hume J.C., Licht M., Burns C.S., Wollenberg K., Simard F.,
RA Ribeiro J.M.;
RT "Molecular evolution of immune genes in the malaria mosquito Anopheles
RT gambiae.";
RL PLoS ONE 4:E4549-E4549(2009).
RN [3] {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 [4]
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 [5] {ECO:0000305}
RP INDUCTION.
RX PubMed=10646969; DOI=10.1016/s0965-1748(99)00095-8;
RA Gorman M.J., Andreeva O.V., Paskewitz S.M.;
RT "Molecular characterization of five serine protease genes cloned from
RT Anopheles gambiae hemolymph.";
RL Insect Biochem. Mol. Biol. 30:35-46(2000).
CC -!- FUNCTION: Probable serine protease which plays a role in the innate
CC immune response against parasite P.bergei infection by activating the
CC melanization cascade (PubMed:16922859). In the resistant strain L3-5,
CC involved in the melanization of killed parasite P.berghei ookinetes
CC which results in their clearance (PubMed:16922859). In the susceptible
CC strain G3, appears to be dispensable for ookinete elimination which
CC occurs by lysis (PubMed:16922859). {ECO:0000269|PubMed:16922859}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: In females, expressed in fat body, cuticle, thorax
CC and ovaries. {ECO:0000269|PubMed:10469250}.
CC -!- DEVELOPMENTAL STAGE: Expressed in eggs, larvae, pupae, and male and
CC female adults. {ECO:0000269|PubMed:10469250}.
CC -!- INDUCTION: Induced following a blood meal (PubMed:10469250). Induced in
CC response to bacterial infection (PubMed:10469250, PubMed:10646969).
CC Induced in response to P.berghei infection (PubMed:16922859,
CC PubMed:10646969). {ECO:0000269|PubMed:10469250,
CC ECO:0000269|PubMed:10646969, ECO:0000269|PubMed:16922859}.
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 -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the resistant strain
CC L3-5 infected with P.berghei, causes a 5-fold reduction in the number
CC of melanized ookinetes (PubMed:16922859). Simultaneous RNAi-mediated
CC knockdown of CLIPB4 and CLIPB17 in the resistant strain L3-5 infected
CC with P.berghei, causes a 52-fold reduction in the number of melanized
CC ookinetes (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). Simultaneous RNAi-mediated
CC knockdown of CLIPB4 and CTL4 in the susceptible strain G3 infected with
CC P.berghei, abolishes ookinete increased melanization caused by RNAi-
CC mediated knockdown of CTL4 (PubMed:16922859).
CC {ECO:0000269|PubMed:16922859}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
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DR EMBL; AF007166; AAB62929.1; -; mRNA.
DR EMBL; FJ653899; ACN38252.1; -; Genomic_DNA.
DR EMBL; AAAB01008794; EAA45573.1; -; Genomic_DNA.
DR RefSeq; XP_307755.1; XM_307755.5.
DR AlphaFoldDB; Q7PEV7; -.
DR SMR; Q7PEV7; -.
DR MEROPS; S01.201; -.
DR PaxDb; Q7PEV7; -.
DR GeneID; 1269159; -.
DR KEGG; aga:AgaP_AGAP003250; -.
DR CTD; 1269159; -.
DR VEuPathDB; VectorBase:AGAP003250; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_0_3_1; -.
DR InParanoid; Q7PEV7; -.
DR OMA; DFISPVC; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q7PEV7; -.
DR Proteomes; UP000007062; Chromosome 2R.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 2: Evidence at transcript 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..360
FT /note="CLIP domain-containing serine protease B4"
FT /evidence="ECO:0000255"
FT /id="PRO_5010132809"
FT DOMAIN 30..83
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 108..360
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 153
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 311
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 31..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 41..72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 47..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 138..154
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 280..297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 307..336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CONFLICT 109
FT /note="I -> L (in Ref. 1; AAB62929 and 2; ACN38252)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="S -> R (in Ref. 1; AAB62929 and 2; ACN38252)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="A -> V (in Ref. 1; AAB62929 and 2; ACN38252)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="I -> V (in Ref. 1; AAB62929 and 2; ACN38252)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="S -> T (in Ref. 1; AAB62929 and 2; ACN38252)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 39382 MW; 992EE1D224B33F09 CRC64;
MIGNRVINLL IVATLALAGQ TVLALELGQD CVNPVGEAGK CVLFRECQPL VDIYNKPVNT
PDDTQFLTES RCGLYERKTL VCCAGVRSKG KTSLPESPNC GVQLTDRVIG GQPTKIDEFP
WTALIEYEKP NGRFGFHCGG SVINERYILT AAHCITSIPR GWKVHRVRLG EWDLSSTTDQ
EDDFYADAPI DLDIEKIIVH PGYNLQDKSH HNDIALIRFN REINYSSTIS AICLPLSNSL
RNRKHAGLSS YAAGWGKTET ASASQKKLKV ELTVVDVKDC SPAYQRNGIS LDSTQMCAGG
IRGKDTCSGD SGGPLMRQMS GSWYLIGVVS FGPQKCGAPG VPGVYTNVAE YVDWIKDNIY
