VSP3_BOTJA
ID VSP3_BOTJA Reviewed; 258 AA.
AC Q9PTU8;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Snake venom serine protease BPA;
DE Short=SVSP;
DE EC=3.4.21.-;
DE AltName: Full=Bothrops protease A;
DE Short=BPA;
DE Flags: Precursor;
OS Bothrops jararaca (Jararaca) (Bothrops jajaraca).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8724;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-57; 109-120 AND 236-248,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC TISSUE=Venom, and Venom gland;
RX PubMed=14580991; DOI=10.1016/j.bbapap.2003.08.001;
RA Murayama N., Saguchi K., Mentele R., Assakura M.T., Ohi H., Fujita Y.,
RA Camargo A.C., Higuchi S., Serrano S.M.;
RT "The unusual high molecular mass of Bothrops protease A, a trypsin-like
RT serine peptidase from the venom of Bothrops jararaca, is due to its high
RT carbohydrate content.";
RL Biochim. Biophys. Acta 1652:1-6(2003).
RN [2]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=14161003; DOI=10.1016/0003-9861(64)90477-1;
RA Mandelbaum F.R., Henriques O.B.;
RT "Purification and properties of Bothrops protease A.";
RL Arch. Biochem. Biophys. 104:369-374(1964).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=18433459; DOI=10.1111/j.1538-7836.2008.02995.x;
RA Paes Leme A.F., Prezoto B.C., Yamashiro E.T., Bertholim L., Tashima A.K.,
RA Klitzke C.F., Camargo A.C.M., Serrano S.M.T.;
RT "Bothrops protease A, a unique highly glycosylated serine proteinase, is a
RT potent, specific fibrinogenolytic agent.";
RL J. Thromb. Haemost. 6:1363-1372(2008).
CC -!- FUNCTION: Snake venom serine protease that has a potent and selective
CC fibrinogenolytic activity. Preferentially cleaves the alpha-chain (FGA)
CC of human and rat fibrinogen at Arg-|-Gly bonds, and slowly digests the
CC beta-chain (FGB) (PubMed:18433459). In vivo, completely avoids thrombus
CC formation induced in rat, decreases the fibrinogen plasma level and
CC prolonges the recalcification time. Possesses esterolytic and
CC amidolytic activities. {ECO:0000269|PubMed:14161003,
CC ECO:0000269|PubMed:18433459}.
CC -!- ACTIVITY REGULATION: Inhibited by diisopropylfluorophosphate (DFP), but
CC not by SBTI, Antithrombin III/heparin and BPTI, probably due to steric
CC hindrance caused by its huge carbohydrate moietie.
CC {ECO:0000269|PubMed:18433459}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.94 mM for Bz-Arg-pNa (at pH 3) {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC KM=0.90 mM for Bz-Arg-pNa (at pH 7.2) {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC KM=0.95 mM for Bz-Arg-pNa (at pH 10) {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC KM=0.29 mM for D-Phe-Pip-Arg-pNA {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC KM=0.31 mM for D-Val-Leu-Arg-pNA {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC KM=0.53 mM for Tos-Gly-Pro-Arg-pNA {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC KM=0.0 mM for D-Val-Leu-Lys-pNA {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC Vmax=0.76 umol/min/mg enzyme with Bz-Arg-pNa as substrate (at pH 3)
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC Vmax=0.82 umol/min/mg enzyme with Bz-Arg-pNa as substrate (at pH 7.2)
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC Vmax=0.75 umol/min/mg enzyme with Bz-Arg-pNa as substrate (at pH 10)
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC Vmax=0.69 nmol/min/mg enzyme with D-Phe-Pip-Arg-pNA as substrate
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC Vmax=0.134 nmol/min/mg enzyme with D-Val-Leu-Arg-pNA as substrate
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC Vmax=0.044 nmol/min/mg enzyme with Tos-Gly-Pro-Arg-pNA as substrate
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC Vmax=0.0 nmol/min/mg enzyme with D-Val-Leu-Lys-pNA as substrate
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459};
CC pH dependence:
CC Optimum pH is 3-9. {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC Temperature dependence:
CC Thermostable. {ECO:0000269|PubMed:14580991,
CC ECO:0000269|PubMed:18433459};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:14580991}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: N- and O-glycosylated. The glycosylation has a stabilizing effect
CC on the protein (PubMed:14580991). However, the removal of part of the
CC carbohydrates enhances the proteolytic activity of the SVSP towards
CC human and rat fibrinogen (PubMed:18433459).
CC {ECO:0000269|PubMed:14580991, ECO:0000269|PubMed:18433459}.
CC -!- MISCELLANEOUS: Does not have coagulant activities and does not cause
CC unspecific degradation of plasma proteins. Does not degrade gamma chain
CC of fibrinogen (FGG) and is not active towards fibrin clots.
CC {ECO:0000305|PubMed:18433459}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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; AB031394; BAA89310.1; -; mRNA.
DR AlphaFoldDB; Q9PTU8; -.
DR SMR; Q9PTU8; -.
DR MEROPS; S01.433; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
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; 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 Direct protein sequencing; Disulfide bond; Fibrinogenolytic toxin;
KW Glycoprotein; Hemostasis impairing toxin; Hydrolase; Protease; Secreted;
KW Serine protease; Signal; Toxin; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT PROPEP 19..24
FT /evidence="ECO:0000269|PubMed:14580991"
FT /id="PRO_0000028383"
FT CHAIN 25..258
FT /note="Snake venom serine protease BPA"
FT /id="PRO_0000028384"
FT DOMAIN 25..249
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 65
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 110
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 204
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT DISULFID 31..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 50..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 98..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 142..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 174..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 200..225
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 258 AA; 28058 MW; 034F49FDCB79EB64 CRC64;
MVLIRVIANL LILQLSNAQK SSELVIGGDE CNITEHRFLV EIFNSSGLFC GGTLIDQEWV
LSAAHCDMRN MRIYLGVHNE GVQHADQQRR FAREKFFCLS SRNYTKWDKD IMLIRLNRPV
NNSEHIAPLS LPSNPPSVGS VCRIMGWGTI TSPNATFPDV PHCANINLFN YTVCRGAHAG
LPATSRTLCA GVLQGGIDTC GGDSGGPLIC NGTFQGIVSW GGHPCAQPGE PALYTKVFDY
LPWIQSIIAG NTTATCPP
