P26324 (VSPF1_CALRH) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Thrombin-like enzyme ancrod Short name=SVTLE EC=3.4.21.74 Alternative name(s): Venombin A
Organism	Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma)
Taxonomic identifier	8717 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Viperidae › Crotalinae › Calloselasma

Protein attributes

Sequence length	234 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Thrombin-like snake venom serine protease that acts as an anticoagulant. It cleaves fibrinogen to split off the A-fibrinopeptides (A, AY and AP), but not the B-fibrinopeptide. The resulting fibrin polymers are imperfectly formed and much smaller in size (1 to 2 um long) than the fibrin polymers produced by the action of thrombin. These ancrod-induced microthrombi are friable, unstable, urea-soluble and have significantly degraded alpha chains. They do not cross-link to form thrombi. They are markedly susceptible to digestion by plasmin and are rapidly removed from circulation by either reticuloendothelial phagocytosis or normal fibrinolysis, or both. Anticoagulation through the removal of fibrinogen from the blood is rapid, occurring within hours following its administration. It does not activate plasminogen and does not degrade preformed, fully cross-linked thrombin fibrin. It also reduces the level of plasminogen activator inhibitor (PAI) and may stimulate the release of tissue plasminogen activator (PLAT) from the endothelium. The profibrinolytic effect of these 2 actions appears to be limited to local microthrombus degradation.
Catalytic activity	Selective cleavage of Arg-|-Xaa bond in fibrinogen, to form fibrin, and release fibrinopeptide A. The specificity of further degradation of fibrinogen varies with species origin of the enzyme.
Subunit structure	Monomer.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Pharmaceutical use	Used for the treatment of acute ischemic stroke. Until 2002 was available under the brand name Arvin or Arwin (Knoll). Is actually available under the brand name Viprinex (Abbott).
Sequence similarities	Belongs to the peptidase S1 family. Snake venom subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Blood coagulation
Cellular component	Secreted
Molecular function	Hydrolase Protease Serine protease Toxin
PTM	Disulfide bond Glycoprotein
Technical term	Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	blood coagulation Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 234	234	Thrombin-like enzyme ancrod		PRO_0000088730
Regions
	Domain	1 – 227	227	Peptidase S1
Sites
	Active site	43	1	Charge relay system By similarity
	Active site	88	1	Charge relay system By similarity
	Active site	182	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	23	1	N-linked (GlcNAc...) Ref.1
	Glycosylation	79	1	N-linked (GlcNAc...) Ref.1
	Glycosylation	99	1	N-linked (GlcNAc...) Ref.1
	Glycosylation	148	1	N-linked (GlcNAc...) Ref.1
	Glycosylation	229	1	N-linked (GlcNAc...) Ref.1
	Disulfide bond	7 ↔ 141		By similarity
	Disulfide bond	28 ↔ 44		By similarity
	Disulfide bond	78 ↔ 232		By similarity
	Disulfide bond	120 ↔ 188		By similarity
	Disulfide bond	152 ↔ 167		By similarity
	Disulfide bond	178 ↔ 203		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P26324 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 3C55F0276B65E5CF	FASTA	234	26,570
	10 20 30 40 50 60 VIGGDECNIN EHRFLVAVYE GTNWTFICGG VLIHPEWVIT AEHCARRRMN LVFGMHRKSE 70 80 90 100 110 120 KFDDEQERYP KKRYFIRCNK TRTSWDEDIM LIRLNKPVNN SEHIAPLSLP SNPPIVGSDC 130 140 150 160 170 180 RVMGWGSINR RIDVLSDEPR CANINLHNFT MCHGLFRKMP KKGRVLCAGD LRGRRDSCNS 190 200 210 220 230 DSGGPLICNE ELHGIVARGP NPCAQPNKPA LYTSIYDYRD WVNNVIAGNA TCSP

References

[1]	"Amino acid sequence determination of ancrod, the thrombin-like alpha-fibrinogenase from the venom of Akistrodon rhodostoma." Burkhart W., Simth G.F.H., Su J.-L., Parikh I., Levine H. III FEBS Lett. 297:297-301(1992) [PubMed: 1544412] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Venom.
+	Additional computationally mapped references.

Web resources

Wikipedia

Ancrod entry

RxMed

Viprinex entry

Cross-references

Sequence databases
PIR	S20407.
3D structure databases
ProteinModelPortal	P26324.
SMR	P26324. Positions 1-233.
ModBase	Search...
Protein family/group databases
MEROPS	S01.178.
PTM databases
GlycoSuiteDB	P26324.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG013304.
Family and domain databases
InterPro	IPR009003. Pept_cys/ser_Trypsin-like. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Pfam	PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. False negative. PS00135. TRYPSIN_SER. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

VSPF1_CALRH

Accession

Primary (citable) accession number: P26324

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	January 25, 2012
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Annotation program

Animal Toxin Annotation Program