Venom prothrombin activator pseutarin-C catalytic subunit precursor - Pseudonaja textilis (Eastern brown snake)

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Q56VR3 (FAXC_PSETE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 70. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names	Recommended name: Venom prothrombin activator pseutarin-C catalytic subunit Short name=PCCS Short name=vPA EC=3.4.21.6 Alternative name(s): Venom coagulation factor Xa-like protease Cleaved into the following 2 chains: Pseutarin-C catalytic subunit light chain Pseutarin-C catalytic subunit heavy chain
Organism	Pseudonaja textilis (Eastern brown snake)
Taxonomic identifier	8673 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Acanthophiinae › Pseudonaja

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Snake prothrombin activator that attacks the hemostatic system of prey. This catalytic subunit is functionally similar to blood coagulation factor Xa. It requires a non-catalytic subunit present in the venom, which is similar to coagulation factor Va, to be fully active. Ref.4
Catalytic activity	Selective cleavage of Arg-\|-Thr and then Arg-\|-Ile bonds in prothrombin to form thrombin. Ref.4
Enzyme regulation	Activated by calcium and negatively charged phospholipids. Ref.4
Subunit structure	Heterodimer of a light and a heavy chains; disulfide-linked. Is associated with pseutarin-C non-catalytic subunit in a non-covalent manner. Ref.4 Ref.5
Subcellular location	Secreted Ref.4 Ref.5.
Tissue specificity	Expressed by the venom gland. Ref.4 Ref.5
Post-translational modification	Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
Toxic dose	Intravenous injection (23 µg/kg bodyweight) of the group C prothrombin activator causes death in rats through disseminated intravascular coagulopathy (Ref.5), whereas pseutarin-C is not lethal even at 10 mg/kg in mice when injected intraperitoneally (Ref.1).
Miscellaneous	Is classified in the group C of snake venom prothrombin activators, since it does not require the mammalian factor Va for the cleavage of prothrombin as the venom contains its own non-catalytic factor Va-like molecule. In contrast to blood coagulation factors that circulate as inactive zymogen in plasma, venom prothrombin activators are always found in the active form in the venom. Hence, catalytic and non-catalytic subunits are found naturally in venom as stable complexes.
Sequence similarities	Belongs to the peptidase S1 family. Contains 2 EGF-like domains. Contains 1 Gla (gamma-carboxy-glutamate) domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
Molecular function	Blood coagulation cascade activating toxin Hemostasis impairing toxin Hydrolase Protease Prothrombin activator Serine protease Toxin
PTM	Cleavage on pair of basic residues Disulfide bond Gamma-carboxyglutamic acid Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological_process	blood coagulation Inferred from electronic annotation. Source: InterPro envenomation resulting in positive regulation of blood coagulation in other organism Inferred from direct assay Ref.4. Source: UniProtKB positive regulation of blood coagulation in other organism Inferred from direct assay Ref.4. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro peptidase activator activity Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

Potential

Propeptide

21 – 40

PRO_0000408523

Chain

41 – 181

141

Pseutarin-C catalytic subunit light chain

PRO_5000090539

Propeptide

182 – 209

Activation peptide By similarity

PRO_0000408525

Chain

210 – 467

258

Pseutarin-C catalytic subunit heavy chain

PRO_0000408526

Regions

Domain

41 – 86

Gla

Domain

86 – 122

EGF-like 1; calcium-binding

Domain

129 – 164

EGF-like 2

Domain

210 – 454

245

Peptidase S1

Sites

Active site

251

Charge relay system By similarity

Active site

309

Charge relay system By similarity

Active site

406

Charge relay system By similarity

Site

Not modified Probable

Site

103

Not modified

Site

209 – 210

Cleavage

Amino acid modifications

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate Ref.4

Modified residue

4-carboxyglutamate By similarity

Modified residue

4-carboxyglutamate By similarity

Glycosylation

O-linked (Hex...) Ref.1

Glycosylation

254

N-linked (GlcNAc...) Ref.1

Disulfide bond

57 ↔ 62

By similarity

Disulfide bond

90 ↔ 101

By similarity

Disulfide bond

95 ↔ 110

By similarity

Disulfide bond

112 ↔ 121

By similarity

Disulfide bond

129 ↔ 140

By similarity

Disulfide bond

136 ↔ 149

By similarity

Disulfide bond

151 ↔ 164

By similarity

Disulfide bond

172 ↔ 329

Interchain (between light and heavy chains) By similarity

Disulfide bond

216 ↔ 221

By similarity

Disulfide bond

236 ↔ 252

By similarity

Disulfide bond

377 ↔ 391

By similarity

Disulfide bond

402 ↔ 430

By similarity

Experimental info

Sequence conflict

V → A in AAP86642. Ref.1

Sequence conflict

193

H → Q in AAP86642. Ref.1

Sequence conflict

196

T → P in AAP86642. Ref.1

Sequence conflict

200

K → I in AAP86642. Ref.1

Sequence conflict

450 – 467

Missing in AAP86642. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q56VR3 [UniParc].

Last modified June 28, 2011. Version 2.
Checksum: C773D41DB08F9844
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FASTA

467

52,215

        10         20         30         40         50         60 
MAPQLLLCLI LTFLWSLPEA ESNVFLKSKV ANRFLQRTKR ANSLVEEFKS GNIERECIEE 

        70         80         90        100        110        120 
RCSKEEAREV FEDDEKTETF WNVYVDGDQC SSNPCHYRGI CKDGIGSYTC TCLSGYEGKN 

       130        140        150        160        170        180 
CERVLYKSCR VDNGNCWHFC KSVQNDIQCS CAEGYLLGED GHSCVAGGNF SCGRNIKTRN 

       190        200        210        220        230        240 
KREASLPDFV QSHNATLLKK SDNPSPDIRI VNGMDCKLGE CPWQAALVDD KKGVFCGGTI 

       250        260        270        280        290        300 
LSPIYVLTAA HCINETETIS VVVGEIDRSR AETGPLLSVD KVYVHKKFVP PKKSQEFYEK 

       310        320        330        340        350        360 
FDLVSYDYDI AIIQMKTPIQ FSENVVPACL PTADFANQVL MKQDFGIVSG FGGIFERGPN 

       370        380        390        400        410        420 
SKTLKVLKVP YVDRHTCMLS SNFPITPTMF CAGYDTLPQD ACQGDSGGPH ITAYRDTHFI 

       430        440        450        460 
TGIVSWGEGC ARKGRYGIYT KLSKFIPWIK RIMRQKLPST ESSTGRL

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References

[1]	"The catalytic subunit of pseutarin C, a group C prothrombin activator from the venom of Pseudonaja textilis, is structurally similar to mammalian blood coagulation factor Xa." Rao V.S., Swarup S., Kini R.M. Thromb. Haemost. 92:509-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 41-70; 77-119; 142-177; 210-242 AND 271-281, TOXIC DOSE, GLYCOSYLATION AT SER-92 AND ASN-254, MASS SPECTROMETRY. Tissue: Venom gland.
[2]	"Cloning and functional expression of venom prothrombin activator protease from Pseudonaja textilis with whole blood procoagulant activity." Filippovich I., Sorokina N., St Pierre L., Flight S., de Jersey J., Perry N., Masci P.P., Lavin M.F. Br. J. Haematol. 131:237-246(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[3]	"Structure of two genes encoding parallel prothrombin activators in Tropidechis carinatus snake: gene duplication and recruitment of factor X gene to the venom gland." Reza M.A., Swarup S., Kini R.M. J. Thromb. Haemost. 5:117-126(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17.
[4]	"Pseutarin C, a prothrombin activator from Pseudonaja textilis venom: its structural and functional similarity to mammalian coagulation factor Xa-Va complex." Rao V.S., Kini R.M. Thromb. Haemost. 88:611-619(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-70 AND 210-246, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GAMMA-CARBOXYGLUTAMATION AT GLU-46; GLU-47; GLU-54; GLU-56; GLU-59; GLU-60; GLU-65 AND GLU-66. Tissue: Venom.
[5]	"Purification and characterization of a prothrombin activator from the venom of the Australian brown snake, Pseudonaja textilis textilis." Masci P.P., Whitaker A.N., de Jersey J. Biochem. Int. 17:825-835(1988) [PubMed] [Europe PMC] [Abstract] Cited for: TOXIC DOSE, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: Pseudonaja textilis textilis. Tissue: Venom.
[6]	"Classification and nomenclature of prothrombin activators isolated from snake venoms." Manjunatha Kini R., Morita T., Rosing J. Thromb. Haemost. 86:710-711(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NOMENCLATURE.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY260939 mRNA. Translation: AAP86642.1. AY631239 mRNA. Translation: AAT42491.1. DQ533835 Genomic DNA. Translation: ABG02407.1.
3D structure databases
ProteinModelPortal	Q56VR3.
SMR	Q56VR3. Positions 42-86, 210-456.
ModBase	Search...
Protein family/group databases
MEROPS	S01.446.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG013304.
Enzyme and pathway databases
BRENDA	3.4.21.60. 6821.
Family and domain databases
Gene3D	4.10.740.10. 1 hit.
InterPro	IPR017857. Coagulation_fac_subgr_Gla_dom. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. IPR000294. GLA_domain. IPR012224. Pept_S1A_FX. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00008. EGF. 1 hit. PF00594. Gla. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PIRSF	PIRSF001143. Factor_X. 1 hit.
PRINTS	PR00722. CHYMOTRYPSIN. PR00001. GLABLOOD.
SMART	SM00181. EGF. 1 hit. SM00179. EGF_CA. 1 hit. SM00069. GLA. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit. SSF57630. VitK_dep_GLA. 1 hit.
PROSITE	PS00010. ASX_HYDROXYL. 1 hit. PS00022. EGF_1. 1 hit. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 1 hit. PS01187. EGF_CA. 1 hit. PS00011. GLA_1. 1 hit. PS50998. GLA_2. 1 hit. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

FAXC_PSETE

Accession

Primary (citable) accession number: Q56VR3
Secondary accession number(s): A5X463, Q6IT09

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 31, 2011
Last sequence update:	June 28, 2011
Last modified:	May 1, 2013
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Annotation program

Animal Toxin Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

Protocols and materials databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents