P82807 (FAXD1_NOTSC) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Notecarin-D1 EC=3.4.21.6 Alternative name(s): Venom coagulation factor Xa-like protease Venom prothrombin activator notecarin-D1 Cleaved into the following 2 chains: Notecarin-D1 light chain Notecarin-D1 heavy chain
Organism	Notechis scutatus scutatus (Mainland tiger snake) (Common tiger snake)
Taxonomic identifier	70142 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Acanthophiinae › Notechis

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 functionally similar to blood coagulation factor Xa. Ref.2 Ref.3
Catalytic activity	Selective cleavage of Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
Subunit structure	Heterodimer of a light chain and a heavy chain; disulfide-linked By similarity.
Subcellular location	Secreted Ref.2 Ref.3.
Tissue specificity	Expressed by the venom gland. Ref.2 Ref.3
Post-translational modification	Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
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. The venom of this species does not contains its own coagulation factor V-like. 2 isoforms of notecarin D (D1 and D2) are described in Ref.3. We chose to name this protein D1 according to the masses indicated in the paper. 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 1 EGF-like domain. Contains 1 Gla (gamma-carboxy-glutamate) domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Blood coagulation
Cellular component	Secreted
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
Molecular function	Hydrolase 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: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro 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
	Signal peptide	1 – 20	20	Potential
	Propeptide	21 – 40	20	By similarity		PRO_0000409723
	Chain	41 – 181	141	Notecarin-D1 light chain		PRO_0000027819
	Propeptide	182 – 209	28	Activation peptide By similarity		PRO_0000409724
	Chain	210 – 455	246	Notecarin-D1 heavy chain		PRO_0000027821
Regions
	Domain	41 – 86	46	Gla
	Domain	86 – 122	37	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
Amino acid modifications
	Modified residue	46	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	47	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	54	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	56	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	59	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	60	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	65	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	66	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	69	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	72	1	4-carboxyglutamate Ref.2 Ref.3
	Modified residue	75	1	4-carboxyglutamate Ref.2 Ref.3
	Glycosylation	92	1	O-linked (Hex...) By similarity
	Glycosylation	254	1	N-linked (GlcNAc...) Potential
	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	216 ↔ 221		By similarity
	Disulfide bond	236 ↔ 252		By similarity
	Disulfide bond	376 ↔ 390		By similarity
	Disulfide bond	401 ↔ 429		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P82807 [UniParc]. Last modified June 28, 2011. Version 2. Checksum: F70377EA9A05BCD2	FASTA	455	51,464
	10 20 30 40 50 60 MAPQLLLCLI LTFLWSLPEA ESNVFLKSKV ANRFLQRTKR SNSLFEEIRP GNIERECIEE 70 80 90 100 110 120 KCSKEEAREV FEDNEKTETF WNVYVDGDQC SSNPCHYRGT CKDGIGSYTC TCLPNYEGKN 130 140 150 160 170 180 CEKVLYQSCR VDNGNCWHFC KRVQSETQCS CAESYRLGVD GHSCVAEGDF SCGRNIKARN 190 200 210 220 230 240 KREASLPDFV QSQKATLLKK SDNPSPDIRI VNGMDCKLGE CPWQAVLINE KGEVFCGGTI 250 260 270 280 290 300 LSPIHVLTAA HCINQTKSVS VIVGEIDISR KETRRLLSVD KIYVHTKFVP PNYYYVHQNF 310 320 330 340 350 360 DRVAYDYDIA IIRMKTPIQF SENVVPACLP TADFANEVLM KQDSGIVSGF GRIRFKEPTS 370 380 390 400 410 420 NTLKVITVPY VDRHTCMLSS DFRITQNMFC AGYDTLPQDA CQGDSGGPHI TAYRDTHFIT 430 440 450 GIISWGEGCA RKGKYGVYTK VSRFIPWIKK IMSLK

References

[1]	"Notecarin D, a prothrombin activator and factor Xa-like protease." Panizzi P.R., Panizzi J.R., Bock P.E. Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[2]	"Identification and purification of vitamin K-dependent proteins and peptides with monoclonal antibodies specific for gamma-carboxyglutamyl (Gla) residues." Brown M.A., Stenberg L.M., Persson U., Stenflo J. J. Biol. Chem. 275:19795-19802(2000) [PubMed: 10779512] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-80; 210-247 AND 296-315, FUNCTION, 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. Tissue: Venom.
[3]	"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 41-76 AND 210-235, FUNCTION, 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, MASS SPECTROMETRY. Tissue: Venom.
[4]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ104218 mRNA. Translation: AAZ14091.1.
3D structure databases
ProteinModelPortal	P82807.
SMR	P82807. Positions 42-86, 210-453.
ModBase	Search...
Protein family/group databases
MEROPS	S01.425.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
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

FAXD1_NOTSC

Accession

Primary (citable) accession number: P82807
Secondary accession number(s): Q4F879

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	June 28, 2011
Last modified:	November 16, 2011
This is version 65 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Annotation program

Chordata Protein Annotation Program