CLB9_ANOGA
ID CLB9_ANOGA Reviewed; 401 AA.
AC F5HKX0; F4YJV1;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=CLIP domain-containing serine protease B9 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000255|RuleBase:RU363034, ECO:0000269|PubMed:20953892, ECO:0000269|PubMed:25525260, ECO:0000269|PubMed:26926112};
DE AltName: Full=Phenoloxidase-activating enzyme B9 {ECO:0000305};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease B9 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease B9 heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=CLIPB9 {ECO:0000303|PubMed:20953892}; Synonyms=11175774;
GN ORFNames=AgaP_AGAP013442 {ECO:0000312|EMBL:EGK96931.1};
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:ADZ72972.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, INTERACTION WITH SRPN2, SUBCELLULAR LOCATION, PROTEOLYTIC
RP CLEAVAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:20953892};
RX PubMed=20953892; DOI=10.1007/s00018-010-0543-z;
RA An C., Budd A., Kanost M.R., Michel K.;
RT "Characterization of a regulatory unit that controls melanization and
RT affects longevity of mosquitoes.";
RL Cell. Mol. Life Sci. 68:1929-1939(2011).
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).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH SRPN2,
RP AND PROTEOLYTIC CLEAVAGE.
RX PubMed=25525260; DOI=10.1074/jbc.m114.625665;
RA Zhang X., Meekins D.A., An C., Zolkiewski M., Battaile K.P., Kanost M.R.,
RA Lovell S., Michel K.;
RT "Structural and inhibitory effects of hinge loop mutagenesis in serpin-2
RT from the malaria vector Anopheles gambiae.";
RL J. Biol. Chem. 290:2946-2956(2015).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC CLEAVAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:26926112};
RX PubMed=26926112; DOI=10.1016/j.ibmb.2016.02.008;
RA Zhang X., An C., Sprigg K., Michel K.;
RT "CLIPB8 is part of the prophenoloxidase activation system in Anopheles
RT gambiae mosquitoes.";
RL Insect Biochem. Mol. Biol. 71:106-115(2016).
CC -!- FUNCTION: Serine protease that functions in the melanization-mediated
CC immune response (PubMed:20953892, PubMed:25525260, PubMed:26926112).
CC Cleaves and activates prophenoloxidase (PPO), which is required for the
CC activation of the prophenoloxidase cascade probably following the
CC recognition of pathogen-derived products (PubMed:20953892,
CC PubMed:26926112). {ECO:0000269|PubMed:20953892,
CC ECO:0000269|PubMed:25525260, ECO:0000269|PubMed:26926112}.
CC -!- ACTIVITY REGULATION: Inhibited by serpin SRPN2.
CC {ECO:0000269|PubMed:20953892, ECO:0000269|PubMed:25525260}.
CC -!- SUBUNIT: Forms a covalent heterodimer with SRPN2; the interaction
CC inhibits CLIPB9 protease activity. {ECO:0000269|PubMed:20953892,
CC ECO:0000269|PubMed:25525260}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000255|RuleBase:RU366078}.
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|RuleBase:RU366078}.
CC -!- PTM: Proteolytic cleavage is necessary for activation.
CC {ECO:0000269|PubMed:20953892, ECO:0000269|PubMed:25525260,
CC ECO:0000269|PubMed:26926112}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in female does not affect
CC lifespan and basal melanization (PubMed:20953892). Simultaneous RNAi-
CC mediated knockdown of SRPN2 and CLIPB9 in female, reduces the
CC spontaneous melanization and the lifespan shortening occurring in SRPN2
CC RNAi-mediated knockdown (PubMed:20953892, PubMed:26926112).
CC {ECO:0000269|PubMed:20953892, ECO:0000269|PubMed:26926112}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|RuleBase:RU366078}.
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DR EMBL; HM070255; ADZ72972.1; -; mRNA.
DR EMBL; AAAB01008879; EGK96931.1; -; Genomic_DNA.
DR RefSeq; XP_003436374.1; XM_003436326.1.
DR AlphaFoldDB; F5HKX0; -.
DR SMR; F5HKX0; -.
DR STRING; 7165.AGAP013442-PC; -.
DR MEROPS; S01.203; -.
DR PaxDb; F5HKX0; -.
DR GeneID; 11175774; -.
DR KEGG; aga:AgaP_AGAP013442; -.
DR CTD; 11175774; -.
DR VEuPathDB; VectorBase:AGAP029769; -.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; F5HKX0; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; F5HKX0; -.
DR Proteomes; UP000007062; Chromosome 2R.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0035008; P:positive regulation of melanization defense response; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
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; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..401
FT /note="CLIP domain-containing serine protease B9"
FT /evidence="ECO:0000255"
FT /id="PRO_5014571538"
FT CHAIN 27..147
FT /note="CLIP domain-containing serine protease B9 light
FT chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455756"
FT CHAIN 148..401
FT /note="CLIP domain-containing serine protease B9 heavy
FT chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455757"
FT DOMAIN 30..85
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 148..400
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 193
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 257
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 353
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT SITE 147..148
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 31..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 41..72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 47..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 178..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 322..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 349..376
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CONFLICT 236
FT /note="I -> V (in Ref. 1; ADZ72972)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 401 AA; 43934 MW; 4D4A8E3D31C3C850 CRC64;
MTSYNRSVAW LTVCVLLALH IGGSHQQQQQ CTTPTRLRGR CISIYECDSI LDYFKQRILT
WEEREFLRKS QCTGATSGRQ PFVCCPGNGS KPVVAPATTV PAGTASTTPA GPAATAPSGD
AALADQLVGG LLPNPKKNEC GVSIGMRIYG GQNADIDEFP WLALLQYENR KGERKYSCGG
SLINRRYVLT AAHCVIGEVE RKEGKLVSVR LGEYNTKTEI DCVTEEQEEI CADPPIDAGI
ESVIVHPGYQ DMAHADDIAL LRLAQSIEYT SFVQPVCLPL TDFRASKTGE VNFVTGFGRT
LQESRSAVKQ KLGIKVYDHA RCQEKYATKN SSITTNQLCA GGEYAKDSCH GDSGGPLMKL
QKVWYLEGIV SYGNRCGLED WPGVYTHVPA YMAWVRSNIK E
