CLB8_ANOGA
ID CLB8_ANOGA Reviewed; 405 AA.
AC Q8MZM7; Q7PGY0;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=CLIP domain-containing serine protease B8 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000269|PubMed:26926112};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease B8 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease B8 heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=CLIPB8 {ECO:0000303|PubMed:16935219};
GN Synonyms=1273740, ser6 {ECO:0000303|Ref.1};
GN ORFNames=AgaP_AGAP003057 {ECO:0000312|EMBL:EAA44761.1};
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:CAD30839.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Volz J.B., Kafatos F.C., Muller H.M.;
RT "PCR-Cloning of a serine protease AgSer6 in Anopheles gambiae.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
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, AND DISRUPTION PHENOTYPE.
RC STRAIN=G3 {ECO:0000269|PubMed:16935219};
RX PubMed=16935219; DOI=10.1016/j.ibmb.2006.06.001;
RA Paskewitz S.M., Andreev O., Shi L.;
RT "Gene silencing of serine proteases affects melanization of Sephadex beads
RT in Anopheles gambiae.";
RL Insect Biochem. Mol. Biol. 36:701-711(2006).
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:16935219, PubMed:26926112). Preferentially,
CC cleaves substrates with an arginine at the P1 site (PubMed:26926112).
CC May be involved in the activation of the prophenoloxidase cascade
CC upstream of CLIPB9; does not cleave prophenoloxidase (PubMed:26926112).
CC {ECO:0000269|PubMed:16935219, ECO:0000269|PubMed:26926112}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
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:O97366}.
CC -!- PTM: Proteolytic cleavage is necessary for activation.
CC {ECO:0000269|PubMed:26926112}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in female does not affect
CC lifespan and basal melanization (PubMed:26926112). Simultaneous RNAi-
CC mediated knockdown of SRPN2 and CLIPB8 in female, reduces the
CC spontaneous melanization and the lifespan shortening occurring in SRPN2
CC RNAi-mediated knockdown (PubMed:26926112). RNAi-mediated knockdown
CC severely reduces the melanization of injected Sephadex beads
CC (PubMed:26926112). {ECO:0000269|PubMed:26926112}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Interacts with serine peptidase inhibitor SRPN2 in vitro;
CC however, SRPN2 does not inhibit CLIPB8 activity suggesting that CLIPB8
CC may not be a physiological target of SRPN2 in vivo.
CC {ECO:0000269|PubMed:26926112}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ459779; CAD30839.1; -; mRNA.
DR EMBL; AAAB01008879; EAA44761.1; -; Genomic_DNA.
DR RefSeq; XP_312743.1; XM_312743.4.
DR AlphaFoldDB; Q8MZM7; -.
DR SMR; Q8MZM7; -.
DR STRING; 7165.AGAP003057-PA; -.
DR MEROPS; S01.507; -.
DR PaxDb; Q8MZM7; -.
DR GeneID; 1273740; -.
DR KEGG; aga:AgaP_AGAP003057; -.
DR CTD; 1273740; -.
DR VEuPathDB; VectorBase:AGAP003057; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_0_3_1; -.
DR InParanoid; Q8MZM7; -.
DR OMA; IRIEQTP; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q8MZM7; -.
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: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; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..405
FT /note="CLIP domain-containing serine protease B8"
FT /evidence="ECO:0000255"
FT /id="PRO_5014589045"
FT CHAIN 25..136
FT /note="CLIP domain-containing serine protease B8 light
FT chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455754"
FT CHAIN 137..405
FT /note="CLIP domain-containing serine protease B8 heavy
FT chain"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT /id="PRO_0000455755"
FT DOMAIN 41..95
FT /note="Clip"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DOMAIN 137..404
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 182
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 249
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 136..137
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 41..94
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 52..84
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 58..95
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT DISULFID 167..183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 322..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 349..380
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 405 AA; 44763 MW; B804AF58868DB7D9 CRC64;
MSSAVLLLLV CGCALAVLSP VAYGAPMDTD DRPVWDSIRL CDIPNEPNPG QCMLPAECVA
YGKINDVSSL SSIERFSFIK QIQCNGSDTV PYVCCPRDSD AYREPYVNET MVPKNRVASR
IAFDADSCGI QSYVAKIRGG QLAEIDEFPW MAMLLYERDN NALTQGCGGA LISRTYVITA
AHCVTGKNFQ QTKGRLKFVR LREYNIHTNP DCVYENDLKD CSDDMIDLVP QAVIPHPEYD
SESSNQQHDI ALIRIEQTPP FTDFLRSICL PEQNFESSAT PGKKLSVSGW GRTDIFKDNL
GPDVLSPIKL KLSLPYVERE KCSKTFRPWS FALGPGQMCA GGERAKDTCA GDSGSPLMSY
DMKRAIWYIT GIVSLGVRGC GVEGLPGVYT NVHHYLPWIK MYTGA
