VM3A2_DEIAC
ID VM3A2_DEIAC Reviewed; 233 AA.
AC A2TK72;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Zinc metalloproteinase recombinant fibrinogenase II;
DE Short=FIIa;
DE Short=rF II;
DE EC=3.4.24.- {ECO:0000269|PubMed:19013210};
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Flags: Fragment;
OS Deinagkistrodon acutus (Hundred-pace snake) (Agkistrodon acutus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Deinagkistrodon.
OX NCBI_TaxID=36307;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TOXIC DOSE.
RC TISSUE=Salivary gland;
RX PubMed=18634754; DOI=10.1016/j.bcp.2008.05.033;
RA Wang R., Qiu P., Jiang W., Cai X., Ou Y., Su X., Cai J., Chen J., Yin W.,
RA Yan G.;
RT "Recombinant fibrinogenase from Agkistrodon acutus venom protects against
RT sepsis via direct degradation of fibrin and TNF-alpha.";
RL Biochem. Pharmacol. 76:620-630(2008).
RN [2]
RP FUNCTION.
RX PubMed=17964518; DOI=10.1016/j.trsl.2007.06.004;
RA Lin X., Liang X.X., Chen J.S., Chen Q., Qiu P.X., Yan G.M.;
RT "The effect of fibrinolytic enzyme FIIa from Agkistrodon acutus venom on
RT disseminated intravascular coagulation in rabbits.";
RL Transl. Res. 150:295-302(2007).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=19013210; DOI=10.1016/j.biochi.2008.10.007;
RA Jiang W., Ma T., Su X., Qiu P., Yan G.;
RT "Enzymatic activities and functional characterization of a novel
RT recombinant snake venom proteinase from Agkistrodon acutus.";
RL Biochimie 91:277-287(2009).
RN [4]
RP FUNCTION.
RX PubMed=19070354; DOI=10.1016/j.thromres.2008.10.017;
RA Wang R., Cai J., Huang Y., Xu D., Sang H., Yan G.;
RT "Novel recombinant fibrinogenase of Agkistrodon acutus venom protects
RT against LPS-induced DIC.";
RL Thromb. Res. 123:919-924(2009).
RN [5]
RP FUNCTION.
RX PubMed=23178656; DOI=10.1016/j.bcp.2012.11.012;
RA Lin X., Qi J.Z., Chen M.H., Qiu B.T., Huang Z.H., Qiu P.X., Chen J.S.,
RA Yan G.M.;
RT "A novel recombinant fibrinogenase of Agkistrodon acutus venom protects
RT against hyperacute rejection via degradation of complements.";
RL Biochem. Pharmacol. 85:772-779(2013).
CC -!- FUNCTION: Snake venom zinc metalloprotease that acts at several levels.
CC It has direct fibrino(geno)lytic activity (Aalpha chain of fibrinogen
CC is cleaved quickly, Bbeta chain slowly, and gamma chain even more
CC slowly) and degradation of TNF-alpha. These activities permit to
CC protect against sepsis and disseminated intravascular coagulation
CC (PubMed:18634754, PubMed:17964518, PubMed:19013210, PubMed:19070354).
CC It inhibits ADP-induced platelet aggregation in human platelet-rich
CC plasma (IC(50)=65.4 ug/ml) (PubMed:19013210). It decreases the activity
CC of complement by degrading human C5, C6 and C9 in vitro, decreasing
CC serum levels of C1q, C3 and C4 in rat, and inhibiting the MAC
CC deposition on HUVECs membrane. This inhibition of complement protects
CC against hyperacute rejection that is the main barrier in
CC xenotransplantation (PubMed:23178656). Has preference for Lys at the P1
CC position. Cleaves insulin B chain at '36-Val-|-Glu-37', '39-Leu-|-Tyr-
CC 40', and '48-Phe-|-Phe-49' bonds. Also cleaves fibronectin and type IV
CC collagen (PubMed:19013210). {ECO:0000269|PubMed:17964518,
CC ECO:0000269|PubMed:18634754, ECO:0000269|PubMed:19013210,
CC ECO:0000269|PubMed:19070354, ECO:0000269|PubMed:23178656}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9PW35};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9PW35};
CC -!- ACTIVITY REGULATION: Inhibited by PMSF and EDTA. Slightly inhibited by
CC Cu(2+) and Zn(2+). Not inhibited by aprotinin, SBTI, Ca(2+), Mg(2+),
CC Na(+) and K(+). {ECO:0000269|PubMed:19013210}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=538.2 uM for N-(p-Tosyl)-Gly-Pro-Lys-pNA
CC {ECO:0000269|PubMed:19013210};
CC pH dependence:
CC Optimum pH is 7.0-10.5. {ECO:0000269|PubMed:19013210};
CC Temperature dependence:
CC Optimum temperature is 30-50 degrees Celsius.
CC {ECO:0000269|PubMed:19013210};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9W6M5}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- TOXIC DOSE: LD(50) is 53.5 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:18634754}.
CC -!- MISCELLANEOUS: This recombinant protein is 95% identical to the
CC peptidase M12B domain of the zinc metalloproteinase-disintegrin-like
CC acurhagin (AC Q9W6M5). {ECO:0000305}.
CC -!- MISCELLANEOUS: Does not activate plasminogen.
CC {ECO:0000269|PubMed:17964518, ECO:0000269|PubMed:19013210}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. {ECO:0000305}.
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DR EMBL; EF210359; ABM92914.1; -; mRNA.
DR AlphaFoldDB; A2TK72; -.
DR SMR; A2TK72; -.
DR MEROPS; M12.334; -.
DR BRENDA; 3.4.24.B39; 191.
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.
PE 1: Evidence at protein level;
KW Calcium; Complement system impairing toxin; Disulfide bond;
KW Fibrinogenolytic toxin; Fibrinolytic toxin; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Secreted; Toxin; Zinc.
FT CHAIN <1..>233
FT /note="Zinc metalloproteinase recombinant fibrinogenase II"
FT /id="PRO_0000432130"
FT DOMAIN 19..215
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT ACT_SITE 156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 22
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 130..210
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 170..194
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 172..177
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT NON_TER 1
FT NON_TER 233
SQ SEQUENCE 233 AA; 26713 MW; DF653A4F318CAA7D CRC64;
KREAEANRTP EQQIYDPYKY VETVFVVDKA MVTKYNGDLD KIKTRMYEAA NNMNEMYRYM
FFRVVMVGLI IWTEEDKITV KPDVDYTLNA FAEWRKTYLL AEKKHDNAQL ITGIDFRGSI
IGYAYIGSMC HPKRSVGIIQ DYSPINLVLA VIMAHEMGHN LGIHHDDGYC YCGGYPCIMG
PSISPEPSKF FSNCSYIQCW DFIMNHNPEC IDNEPLGTDI ISPPLCGNEL LEA
