VM1N_BOTPA
ID VM1N_BOTPA Reviewed; 198 AA.
AC Q9I9R4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Snake venom metalloproteinase neuwiedase;
DE Short=SVMP;
DE EC=3.4.24.-;
DE Flags: Fragment;
OS Bothrops pauloensis (Neuwied's lancehead) (Bothrops neuwiedi pauloensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=1042543;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-20 AND 141-155, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11032408; DOI=10.1006/abbi.2000.1958;
RA Rodrigues V.M., Soares A.M., Guerra-Sa R., Rodrigues V., Fontes M.R.M.,
RA Giglio J.R.;
RT "Structural and functional characterization of neuwiedase, a nonhemorrhagic
RT fibrin(ogen)olytic metalloprotease from Bothrops neuwiedi snake venom.";
RL Arch. Biochem. Biophys. 381:213-224(2000).
RN [2]
RP FUNCTION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=11506891; DOI=10.1016/s0300-9084(01)01282-2;
RA Rodrigues V.M., Soares A.M., Andriao-Escarso S.H., Franceschi A.M.,
RA Rucavado A., Gutierrez J.M., Giglio J.R.;
RT "Pathological alterations induced by neuwiedase, a metalloproteinase
RT isolated from Bothrops neuwiedi snake venom.";
RL Biochimie 83:471-479(2001).
RN [3]
RP FUNCTION, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=14505822; DOI=10.1016/s0300-9084(03)00126-3;
RA Izidoro L.F.M., Rodrigues V.M., Rodrigues R.S., Ferro E.V., Hamaguchi A.,
RA Giglio J.R., Homsi-Brandeburgo M.I.;
RT "Neutralization of some hematological and hemostatic alterations induced by
RT neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi pauloensis
RT snake venom, by the aqueous extract from Casearia mariquitensis
RT (Flacourtiaceae).";
RL Biochimie 85:669-675(2003).
CC -!- FUNCTION: This non-hemorrhagic metalloprotease hydrolyzes the Aalpha
CC chain of fibrin and fibrinogen first followed by the Bbeta chain and
CC shows no effect on the gamma chain. It is also able to degrade type I
CC collagen, fibronectin, laminin and induces inflammatory reaction. It is
CC devoid of hemorrhagic and thrombotic activities, but induces pulmonary
CC bleeding. It also induces a mild myotoxic reaction. It is not able to
CC inhibit platelet aggregation, but it induces decrease of platelets and
CC plasma fibrinogen. It contributes to local tissue damage by inducing
CC edema, inflammatory infiltrate and mild myotoxicity, and by degrading
CC extracellular matrix components. Cleaves insulin B chain at '38-Ala-|-
CC Leu-39' and '40-Tyr-|-Leu-41' bonds (PubMed:11032408).
CC {ECO:0000269|PubMed:11032408, ECO:0000269|PubMed:11506891,
CC ECO:0000269|PubMed:14505822}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA, EGTA and 1,10-phenanthroline,
CC partially inhibited by beta-mercaptoethanol and not inhibited by serine
CC protease inhibitors (leupeptin and aprotinin). Also inhibited by an
CC excess of zinc, mercury and magnesium ions. Extracts of the plant
CC Casearia mariquitensis neutralizes the decrease of platelets and plasma
CC fibrinogen induced by the protease. The same extracts also partially
CC inhibit Bbeta chain cleavage, but not Aalpha chain cleavage.
CC {ECO:0000269|PubMed:11032408, ECO:0000269|PubMed:14505822}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.4-8.0. {ECO:0000269|PubMed:11032408};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:11032408};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 5 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:11506891}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-I
CC subfamily. {ECO:0000305}.
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DR EMBL; AF226274; AAF28364.1; -; mRNA.
DR AlphaFoldDB; Q9I9R4; -.
DR SMR; Q9I9R4; -.
DR BindingDB; Q9I9R4; -.
DR ChEMBL; CHEMBL4295953; -.
DR MEROPS; M12.312; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF01421; Reprolysin; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Direct protein sequencing; Disulfide bond; Fibrinogenolytic toxin;
KW Fibrinolytic toxin; Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW Metalloprotease; Myotoxin; Protease; Secreted; Toxin; Zinc.
FT CHAIN 1..>198
FT /note="Snake venom metalloproteinase neuwiedase"
FT /id="PRO_0000326273"
FT DOMAIN 8..>198
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT ACT_SITE 145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 11
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT DISULFID 159..183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 161..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT NON_TER 198
SQ SEQUENCE 198 AA; 22524 MW; 3A81D1711837571B CRC64;
QQRFFPQRYI ELVIVADRRM YTKYNSDSNK IRTRVHELVN TVNGFFRSMN VDASLANLEV
WSKKDLIKVE KDSSKTLTSF GEWRERDLLR RKSHDNAQLL TAIDFNGNTI GRAYLGSMCN
PKRSVGIVQD HSPINLLVGV TMAHELGHNL GMEHDGKDCL CGASLCIMSP GLTDGPSYEF
SDCSKDYYQT FLTNHNPQ
