HP8_BOMMO
ID HP8_BOMMO Reviewed; 369 AA.
AC Q2VG86; H9J6N1; Q8I924;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=CLIP domain-containing serine protease HP8 {ECO:0000305|PubMed:26707571};
DE EC=3.4.21.- {ECO:0000269|PubMed:16399077, ECO:0000269|PubMed:7737188};
DE AltName: Full=BzArgOEtase {ECO:0000303|PubMed:7737188};
DE Short=BAEEase {ECO:0000303|PubMed:16399077};
DE AltName: Full=Hemolymph proteinase 8 {ECO:0000303|PubMed:26707571};
DE Short=HP8 {ECO:0000303|PubMed:26707571};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease HP8 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=CLIP domain-containing serine protease HP8 heavy chain {ECO:0000305};
DE Flags: Precursor;
OS Bombyx mori (Silk moth).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Bombycoidea;
OC Bombycidae; Bombycinae; Bombyx.
OX NCBI_TaxID=7091 {ECO:0000312|EMBL:ABB58762.1};
RN [1] {ECO:0000312|EMBL:BAE73254.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-28; 84-87 AND 113-116,
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, PROTEOLYTIC CLEAVAGE, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Kinshu X Showa {ECO:0000312|EMBL:BAE73254.1};
RC TISSUE=Fat body {ECO:0000312|EMBL:BAE73254.1};
RX PubMed=16399077; DOI=10.1016/j.devcel.2005.11.013;
RA Jang I.H., Chosa N., Kim S.H., Nam H.J., Lemaitre B., Ochiai M.,
RA Kambris Z., Brun S., Hashimoto C., Ashida M., Brey P.T., Lee W.J.;
RT "A Spatzle-processing enzyme required for toll signaling activation in
RT Drosophila innate immunity.";
RL Dev. Cell 10:45-55(2006).
RN [2] {ECO:0000312|EMBL:AAL31707.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Park D.-S., Park H.-Y.;
RT "Hemolymph prophenoloxidase activating factor from Bombyx mori.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:ABB58762.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chosa N., Jang I., Lee W., Ashida M.;
RT "Isolation and characterization of pro-BAEEase from Bombyx mori.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=p50T;
RX PubMed=19121390; DOI=10.1016/j.ibmb.2008.11.004;
RG International Silkworm Genome Consortium;
RT "The genome of a lepidopteran model insect, the silkworm Bombyx mori.";
RL Insect Biochem. Mol. Biol. 38:1036-1045(2008).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=7737188; DOI=10.1111/j.1432-1033.1995.tb20334.x;
RA Katsumi Y., Kihara H., Ochiai M., Ashida M.;
RT "A serine protease zymogen in insect plasma. Purification and activation by
RT microbial cell wall components.";
RL Eur. J. Biochem. 228:870-877(1995).
RN [6]
RP NOMENCLATURE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION BY BACTERIA AND FUNGI.
RX PubMed=26707571; DOI=10.1016/j.ibmb.2015.12.005;
RA Shu M., Mang D., Fu G.S., Tanaka S., Endo H., Kikuta S., Sato R.;
RT "Mechanisms of nodule-specific melanization in the hemocoel of the
RT silkworm, Bombyx mori.";
RL Insect Biochem. Mol. Biol. 70:10-23(2016).
RN [7]
RP FUNCTION.
RX PubMed=34022191; DOI=10.1016/j.jinsphys.2021.104252;
RA Tokunaga K., Tezuka M., Tang S., Shu M., Yamagishi T., Sato R.;
RT "A humoral factor, hemolymph proteinase 8, elicits a cellular defense
RT response of nodule formation in Bombyx mori larvae in association with
RT recognition by C-type lectins.";
RL J. Insect Physiol. 132:104252-104252(2021).
CC -!- FUNCTION: Endopeptidase with selective post-Arg cleavage site
CC (PubMed:16399077, PubMed:7737188). Functions in the innate immune
CC response to fungal and Gram-positive bacterial infections
CC (PubMed:16399077, PubMed:26707571, PubMed:34022191). Upon pathogen
CC infection promotes nodulation; a cellular defense response in which
CC hemocytes surround and isolate invading pathogens forming aggregates
CC called nodules (PubMed:26707571, PubMed:34022191). Involved in
CC activating nodule formation in response to infection with M.luteus, E.
CC coli or S.cerevisiae (PubMed:34022191). Able to bind the microbes
CC M.luteus, E. coli or S.cerevisiae (PubMed:34022191). According to
CC another report, does not bind microorganisms (PubMed:26707571).
CC {ECO:0000269|PubMed:16399077, ECO:0000269|PubMed:26707571,
CC ECO:0000269|PubMed:34022191, ECO:0000269|PubMed:7737188}.
CC -!- ACTIVITY REGULATION: Inhibited by (p-amidinophenyl) methanesulfonyl
CC fluoride, p-nitrophenyl-p'-guanidinobenzoate, D-phenylalanyl-L-prolyl-
CC L-arginyl chloromethane, leupeptin, antipain and to a lesser extent by
CC antithrombin III. {ECO:0000269|PubMed:7737188}.
CC -!- SUBUNIT: In the active form, heterodimer of a light chain and a heavy
CC chain; disulfide-linked. {ECO:0000305|PubMed:16399077}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16399077,
CC ECO:0000269|PubMed:26707571, ECO:0000269|PubMed:7737188}. Cytoplasm
CC {ECO:0000269|PubMed:26707571}. Note=In larvae, secreted in the
CC hemolymph (PubMed:16399077, PubMed:7737188, PubMed:26707571). Only the
CC uncleaved form is detected in hemolymph (PubMed:26707571). Uncleaved
CC (42 kDa) and cleaved (29 kDa) forms, are weakly expressed in hemocytes
CC (PubMed:26707571). Detected in the cytoplasm of various hemocytes
CC including plasmatocytes, oenocytoids, granulocytes and prohemocytes
CC (PubMed:26707571). Cleaved and uncleaved forms also localize to immune
CC defense nodules that have been induced by injection with E.coli,
CC M.luteus or S.cerevisiae cells (PubMed:26707571).
CC {ECO:0000269|PubMed:16399077, ECO:0000269|PubMed:26707571,
CC ECO:0000269|PubMed:7737188}.
CC -!- TISSUE SPECIFICITY: In larvae, expressed in the fat body and hemocytes.
CC {ECO:0000269|PubMed:26707571}.
CC -!- INDUCTION: Up-regulated in plasma in response to infection with
CC S.cerevisiae and M.luteus. {ECO:0000269|PubMed:26707571}.
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: Proteolytically cleaved for activation (PubMed:16399077). Cleavage
CC produces a light chain and a catalytic heavy chain which remains
CC covalently associated probably through an interchain disulfide bond
CC (Probable). {ECO:0000269|PubMed:16399077, ECO:0000305|PubMed:16399077}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
CC -!- CAUTION: The light chain lacks the CLIP domain which is different from
CC other CLIP protease family members. This is due to a cleavage at
CC position 83 which is seen in vitro but whose physiological relevance is
CC unclear. {ECO:0000269|PubMed:16399077}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL31707.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BABH01019990; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AB035418; BAE73254.1; -; mRNA.
DR EMBL; AY061936; AAL31707.1; ALT_FRAME; mRNA.
DR EMBL; DQ157441; ABB58762.1; -; mRNA.
DR EMBL; BABH01019990; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001036844.1; NM_001043379.1.
DR AlphaFoldDB; Q2VG86; -.
DR SMR; Q2VG86; -.
DR STRING; 7091.BGIBMGA005173-TA; -.
DR MEROPS; S01.507; -.
DR GeneID; 692384; -.
DR KEGG; bmor:692384; -.
DR CTD; 692384; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_0_3_1; -.
DR OrthoDB; 1314811at2759; -.
DR Proteomes; UP000005204; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; 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 Calcium; Cleavage on pair of basic residues; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Metal-binding; Protease; Reference proteome; Secreted; Serine protease;
KW Signal; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:16399077"
FT PROPEP 25..81
FT /evidence="ECO:0000305"
FT /id="PRO_0000443325"
FT CHAIN 84..112
FT /note="CLIP domain-containing serine protease HP8 light
FT chain"
FT /evidence="ECO:0000305|PubMed:16399077"
FT /id="PRO_0000443326"
FT CHAIN 113..369
FT /note="CLIP domain-containing serine protease HP8 heavy
FT chain"
FT /evidence="ECO:0000305|PubMed:16399077"
FT /id="PRO_0000443327"
FT DOMAIN 26..75
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 113..368
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 157
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 219
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 317
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 182
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT SITE 83..84
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:16399077"
FT SITE 112..113
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:16399077"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 27..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 33..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 39..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 105..239
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 142..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 186..191
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 286..303
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 313..344
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 369 AA; 40744 MW; 0869ACFE1898CBA4 CRC64;
MKTPFEKIRI ISCILVIVST NVVGQKCNGG ANCIPLEECT DLFQQLKQGN SPQLTRLLRG
LHCGFEDLNS PKICCPPEFL ARRSAFSSAG TNSNPTSILP NEKVCGIQNN DRIFGGIQTE
IDEHPWMALL RYDKPLGWGF YCGGVLIAPM YVLTAAHCVK GSDLPSSWQL SQVRLGEWNT
STETDCVEGD CSGPVQDIPV QQIIAHENYD PNDKDQQNDI ALLRLSRNAQ FNDFVSPICL
PTSNELRQNE FESDYMEVAG WGKTETRSES DVKLKVRVPI VNREECANVY SNVDRRVTNK
QICAGGLAGR DSCRGDSGGA LMGQSPKANN WYVFGVVSYG PSPCGTEGWP GVYTRVGSFM
DWILSKLEQ
