P83370 (FAXD_HOPST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Hopsarin-D EC=3.4.21.6 Alternative name(s): Venom coagulation factor Xa-like protease Venom prothrombin activator hopsarin-D Short name=vPA hopsarin-D Cleaved into the following 2 chains: Hopsarin-D light chain Hopsarin-D heavy chain
Organism	Hoplocephalus stephensii (Stephens' banded snake)
Taxonomic identifier	196418 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Notechinae › Hoplocephalus

Protein attributes

Sequence length	455 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 protein is functionaly similar to blood coagulation factor Xa. The procoagulant activity of hopsarin-D is approximately 10-fold lower than that of trocarin-D and FXa. Ref.2
Catalytic activity	Selective cleavage of Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin. Ref.2
Subunit structure	Heterodimer of a light chain and a heavy chain; disulfide-linked. Ref.2
Subcellular location	Secreted Ref.2.
Tissue specificity	Expressed by the venom gland. Ref.2
Post-translational modification	The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium By similarity. UniProtKB P00742
Miscellaneous	Is classified in the group D of snake venom prothrombin activators, since it requires the mammalian factor Va for maximal activity for the cleavage of prothrombin. 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.
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.
Caution	Lacks the Cys residue in position 216 that is replaced by a Ser residue, resulting of a loss a disulfide bond. This may contribute to the lower procoagulant activity.

Ontologies

Keywords
Biological process	Blood coagulation
Cellular component	Secreted
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
Molecular function	Hydrolase Protease Serine protease Toxin
PTM	Disulfide bond Gamma-carboxyglutamic acid Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Non-traceable author statement. Source: UniProtKB pathogenesis Non-traceable author statement. Source: UniProtKB proteolysis Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	calcium ion binding Non-traceable author statement. Source: UniProtKB serine-type endopeptidase activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Propeptide	21 – 40	20	By similarity		PRO_0000409722
	Chain	41 – 181	141	Hopsarin-D light chain		PRO_0000027816
	Propeptide	182 – 209	28	Activation peptide		PRO_5000095361
	Chain	210 – 455	246	Hopsarin-D heavy chain		PRO_0000027817
Regions
	Domain	41 – 86	46	Gla
	Domain	86 – 121	36	EGF-like 1; calcium-binding
	Domain	129 – 164	36	EGF-like 2
	Domain	210 – 453	244	Peptidase S1
Sites
	Active site	251	1	Charge relay system By similarity
	Active site	308	1	Charge relay system By similarity
	Active site	405	1	Charge relay system By similarity
	Site	103	1	Not modified
Amino acid modifications
	Modified residue	46	1	4-carboxyglutamate Ref.2
	Modified residue	47	1	4-carboxyglutamate Ref.2
	Modified residue	54	1	4-carboxyglutamate Ref.2
	Modified residue	56	1	4-carboxyglutamate Ref.2
	Modified residue	59	1	4-carboxyglutamate Ref.2
	Modified residue	60	1	4-carboxyglutamate Ref.2
	Modified residue	65	1	4-carboxyglutamate Ref.2
	Modified residue	66	1	4-carboxyglutamate Ref.2
	Modified residue	69	1	4-carboxyglutamate Ref.2
	Modified residue	72	1	4-carboxyglutamate Ref.2
	Modified residue	75	1	4-carboxyglutamate Ref.2
	Glycosylation	92	1	O-linked (Hex...) Ref.2
	Glycosylation	254	1	N-linked (GlcNAc...) Ref.2
	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 ↔ 328		Interchain (between light and heavy chains) By similarity
	Disulfide bond	236 ↔ 252		By similarity
	Disulfide bond	376 ↔ 390		By similarity
	Disulfide bond	401 ↔ 429		By similarity
Experimental info
	Sequence conflict	78	1	E → T AA sequence Ref.2
	Sequence conflict	98	1	H → R AA sequence Ref.2
	Sequence conflict	260 – 270	11	Missing AA sequence Ref.2
	Sequence conflict	402	1	E → Q AA sequence Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P83370 [UniParc]. Last modified June 28, 2011. Version 2. Checksum: 39B5F4442B995E4F	FASTA	455	51,248
	10 20 30 40 50 60 MAPQLLLCLI LTFLWSVPEA ESNVFLKSKV ANRFLQRTKR SNSLFEEIRP GNIERECIEE 70 80 90 100 110 120 KCSKEEAREV FEDNEKTETF WNVYVDGDQC SSNPCHYHGT CKDGIGSYTC TCLPNYEGKN 130 140 150 160 170 180 CEKVLFKSCR AFNGNCWHFC KRVQSETQCS CAESYRLGVD GHSCVAEGDF SCGRNIKARN 190 200 210 220 230 240 KREASLPDFV QSQKATLLKK SDNPSPDIRI VNGMDSKLGE CPWQAVLINE KGEVFCGGTI 250 260 270 280 290 300 LSPIHVLTAA HCINQTKSVS VIVGEIDISR KETRRLLSVD KIYVHTKFVP PNYYYGHQNF 310 320 330 340 350 360 DRVAYDYDIA IIRMKTPIQF SENVVPACLP TADFANEVLM KQDSGIVSGF GRIRFKEPTS 370 380 390 400 410 420 NTLKVITVPY VDRHTCMLSS DFRITQNMFC AGYDTLPQDA CEGDSGGPHI TAYGDTHFIT 430 440 450 GIVSWGEGCA RKGKYGVYTK VSRFIPWIKK IMSLK

References

[1]	"Comparative analysis of prothrombin activators from the venom of Australian elapids." St Pierre L., Masci P.P., Filippovich I., Sorokina N., Marsh N., Miller D.J., Lavin M.F. Mol. Biol. Evol. 22:1853-1864(2005) [PubMed: 15930152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[2]	"Group D prothrombin activators from snake venom are structural homologues of mammalian blood coagulation factor Xa." Rao V.S., Joseph J.S., Kini R.M. Biochem. J. 369:635-642(2003) [PubMed: 12403650] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-181 AND 210-455, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GAMMA-CARBOXYGLUTAMATION AT GLU-46; GLU-47; GLU-54; GLU-56; GLU-59; GLU-60; GLU-65; GLU-66; GLU-69; GLU-72 AND GLU-75, GLYCOSYLATION AT SER-92 AND ASN-254, MASS SPECTROMETRY. Tissue: Venom.
[3]	"Classification and nomenclature of prothrombin activators isolated from snake venoms." Manjunatha Kini R., Morita T., Rosing J. Thromb. Haemost. 86:710-711(2001) [PubMed: 11522026] [Abstract] Cited for: NOMENCLATURE.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY940208 mRNA. Translation: AAX37264.1.
3D structure databases
ProteinModelPortal	P83370.
SMR	P83370. Positions 42-86, 210-453.
ModBase	Search...
Protein family/group databases
MEROPS	S01.426.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG013304.
Family and domain databases
InterPro	IPR017857. Coagulation_fac_subgr_Gla_dom. IPR006209. EGF. IPR006210. EGF-like. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR000742. EGF_3. IPR018097. EGF_Ca-bd_CS. IPR000294. GLA_domain. IPR009003. Pept_cys/ser_Trypsin-like. IPR012224. Pept_S1A_FX. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Gene3D	G3DSA:4.10.740.10. Coagulation_factor_Gla. 1 hit.
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. False negative. 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

FAXD_HOPST

Accession

Primary (citable) accession number: P83370
Secondary accession number(s): Q58L92

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2003
Last sequence update:	June 28, 2011
Last modified:	November 16, 2011
This is version 72 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