VM1F_AGKCO
ID VM1F_AGKCO Reviewed; 203 AA.
AC P28891; Q9PS71;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Snake venom metalloproteinase fibrolase {ECO:0000303|PubMed:1304358};
DE Short=SVMP;
DE EC=3.4.24.72;
DE AltName: Full=Fibrinolytic metalloproteinase {ECO:0000303|PubMed:1304358};
DE Short=Fibrinolytic proteinase;
DE AltName: INN=Alfimeprase {ECO:0000303|PubMed:11369866, ECO:0000303|PubMed:18632486};
OS Agkistrodon contortrix contortrix (Southern copperhead).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX NCBI_TaxID=8713;
RN [1]
RP PROTEIN SEQUENCE, PYROGLUTAMATE FORMATION AT GLN-1, DISULFIDE BOND
RP (PARTIAL), VARIANTS GLN-2 DEL; GLU-189 AND LEU-192, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=1304358; DOI=10.1002/pro.5560010505;
RA Randolph A., Chamberlain S.H., Chu H.L.C., Retzios A.D., Markland F.S. Jr.,
RA Masiarz F.R.;
RT "Amino acid sequence of fibrolase, a direct-acting fibrinolytic enzyme from
RT Agkistrodon contortrix contortrix venom.";
RL Protein Sci. 1:590-600(1992).
RN [2]
RP PROTEIN SEQUENCE OF 141-151, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1898066; DOI=10.1016/0003-9861(91)90462-r;
RA Guan A.L., Retzios A.D., Henderson G.N., Markland F.S. Jr.;
RT "Purification and characterization of a fibrinolytic enzyme from venom of
RT the southern copperhead snake (Agkistrodon contortrix contortrix).";
RL Arch. Biochem. Biophys. 289:197-207(1991).
RN [3]
RP DISULFIDE BONDS.
RX PubMed=11369866; DOI=10.1110/ps.110101;
RA Jones G., Ronk M., Mori F., Zhang Z.;
RT "Disulfide structure of alfimeprase: a recombinant analog of fibrolase.";
RL Protein Sci. 10:1264-1267(2001).
RN [4]
RP PHARMACEUTICAL.
RX PubMed=18632486; DOI=10.3816/sct.2006.n.010;
RA Reddy G.K.;
RT "Clinical utility of novel agents in the treatment of central venous
RT catheter occlusion.";
RL Support. Cancer Ther. 3:135-139(2006).
CC -!- FUNCTION: Snake venom zinc metalloprotease that exhibits direct
CC fibrinolytic activity.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of 14-Ala-|-Leu-15 in insulin B chain and 413-
CC Lys-|-Leu-414 in alpha-chain of fibrinogen.; EC=3.4.24.72;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Is inhibited by EDTA, o-phenanthroline and
CC tetraethylenepentamine. {ECO:0000269|PubMed:1898066}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1304358,
CC ECO:0000269|PubMed:1898066}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1304358, ECO:0000305|PubMed:1898066}.
CC -!- PHARMACEUTICAL: Failed the phase III clinical trial for the treatment
CC of arterial occlusive disease and acute ischemic stroke.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-I
CC subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P28891; -.
DR SMR; P28891; -.
DR MEROPS; M12.133; -.
DR BRENDA; 3.4.24.72; 192.
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:UniProtKB-EC.
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 Direct protein sequencing; Disulfide bond; Fibrinolytic toxin;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Pharmaceutical; Protease; Pyrrolidone carboxylic acid; Secreted; Toxin;
KW Zinc.
FT CHAIN 1..203
FT /note="Snake venom metalloproteinase fibrolase"
FT /evidence="ECO:0000269|PubMed:1304358"
FT /id="PRO_0000078197"
FT DOMAIN 7..203
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT ACT_SITE 144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT MOD_RES 1
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:1304358"
FT DISULFID 118..198
FT /evidence="ECO:0000269|PubMed:11369866,
FT ECO:0000269|PubMed:1304358"
FT DISULFID 158..182
FT /evidence="ECO:0000269|PubMed:11369866"
FT DISULFID 160..165
FT /evidence="ECO:0000269|PubMed:11369866"
FT VARIANT 2
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:1304358"
FT VARIANT 189
FT /note="T -> E"
FT /evidence="ECO:0000269|PubMed:1304358"
FT VARIANT 192
FT /note="T -> L"
FT /evidence="ECO:0000269|PubMed:1304358"
SQ SEQUENCE 203 AA; 22908 MW; 646EBE6F7F1EA191 CRC64;
QQRFPQRYVQ LVIVADHRMN TKYNGDSDKI RQWVHQIVNT INEIYRPLNI QFTLVGLEIW
SNQDLITVTS VSHDTLASFG NWRETDLLRR QRHDNAQLLT AIDFDGDTVG LAYVGGMCQL
KHSTGVIQDH SAINLLVALT MAHELGHNLG MNHDGNQCHC GANSCVMAAM LSDQPSKLFS
DCSKKDYQTF LTVNNPQCIL NKP
