ID   VSPF1_CALRH             Reviewed;         234 AA.
AC   P26324;
DT   01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1992, sequence version 1.
DT   02-SEP-2026, entry version 115.
DE   RecName: Full=Thrombin-like enzyme ancrod;
DE            Short=SVTLE;
DE            EC=3.4.21.74;
DE   AltName: Full=Fibrinogen-clotting enzyme;
DE   AltName: Full=Snake venom serine protease;
DE            Short=SVSP;
DE   AltName: Full=Venombin A;
OS   Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Calloselasma.
OX   NCBI_TaxID=8717;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Venom;
RX   PubMed=1544412; DOI=10.1016/0014-5793(92)80559-y;
RA   Burkhart W., Simth G.F.H., Su J.-L., Parikh I., Levine H. III;
RT   "Amino acid sequence determination of ancrod, the thrombin-like alpha-
RT   fibrinogenase from the venom of Akistrodon rhodostoma.";
RL   FEBS Lett. 297:297-301(1992).
CC   -!- FUNCTION: Thrombin-like snake venom serine protease that acts as an
CC       anticoagulant. It cleaves fibrinogen (FGA) to split off the A-
CC       fibrinopeptides (A, AY and AP), but not the B-fibrinopeptide. The
CC       resulting fibrin polymers are imperfectly formed and much smaller in
CC       size (1 to 2 um long) than the fibrin polymers produced by the action
CC       of thrombin. These ancrod-induced microthrombi are friable, unstable,
CC       urea-soluble and have significantly degraded alpha chains. They do not
CC       cross-link to form thrombi. They are markedly susceptible to digestion
CC       by plasmin and are rapidly removed from circulation by either
CC       reticuloendothelial phagocytosis or normal fibrinolysis, or both.
CC       Anticoagulation through the removal of fibrinogen from the blood is
CC       rapid, occurring within hours following its administration. It does not
CC       activate plasminogen and does not degrade preformed, fully cross-linked
CC       thrombin fibrin. It also reduces the level of plasminogen activator
CC       inhibitor (PAI) and may stimulate the release of tissue plasminogen
CC       activator (PLAT) from the endothelium. The profibrinolytic effect of
CC       these 2 actions appears to be limited to local microthrombus
CC       degradation.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Selective cleavage of Arg-|-Xaa bond in fibrinogen, to form
CC         fibrin, and release fibrinopeptide A. The specificity of further
CC         degradation of fibrinogen varies with species origin of the enzyme.;
CC         EC=3.4.21.74;
CC   -!- SUBUNIT: Monomer.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- PHARMACEUTICAL: Used for the treatment of acute ischemic stroke. Until
CC       2002 was available under the brand name Arvin or Arwin (Knoll). Is
CC       actually available under the brand name Viprinex (Abbott).
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Ancrod entry;
CC       URL="https://en.wikipedia.org/wiki/Ancrod";
CC   -!- WEB RESOURCE: Name=RxMed; Note=Viprinex entry;
CC       URL="https://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/cps-_monographs/CPS-_(General_Monographs-_V)/VIPRINEX.html";
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DR   PIR; S20407; S20407.
DR   AlphaFoldDB; P26324; -.
DR   SMR; P26324; -.
DR   MEROPS; S01.178; -.
DR   GlyConnect; P26324; 24 N-Linked glycans.
DR   iPTMnet; P26324; -.
DR   BRENDA; 3.4.21.74; 198.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030141; C:secretory granule; IEA:TreeGrafter.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   FunFam; 2.40.10.10:FF:000010; Kallikrein related peptidase 11; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   PANTHER; PTHR24271:SF47; KALLIKREIN-1; 1.
DR   PANTHER; PTHR24271; KALLIKREIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
PE   1: Evidence at protein level;
KW   Blood coagulation cascade inhibiting toxin; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Hemostasis impairing toxin; Hydrolase;
KW   Pharmaceutical; Protease; Secreted; Serine protease; Toxin.
FT   CHAIN           1..234
FT                   /note="Thrombin-like enzyme ancrod"
FT                   /id="PRO_0000088730"
FT   DOMAIN          1..227
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        43
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        88
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        182
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   CARBOHYD        23
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1544412"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1544412"
FT   CARBOHYD        99
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1544412"
FT   CARBOHYD        148
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1544412"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:1544412"
FT   DISULFID        7..141
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        28..44
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        78..232
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        120..188
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        152..167
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        178..203
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ   SEQUENCE   234 AA;  26570 MW;  3C55F0276B65E5CF CRC64;
     VIGGDECNIN EHRFLVAVYE GTNWTFICGG VLIHPEWVIT AEHCARRRMN LVFGMHRKSE
     KFDDEQERYP KKRYFIRCNK TRTSWDEDIM LIRLNKPVNN SEHIAPLSLP SNPPIVGSDC
     RVMGWGSINR RIDVLSDEPR CANINLHNFT MCHGLFRKMP KKGRVLCAGD LRGRRDSCNS
     DSGGPLICNE ELHGIVARGP NPCAQPNKPA LYTSIYDYRD WVNNVIAGNA TCSP
//