VSPH1_VIPAA
ID VSPH1_VIPAA Reviewed; 260 AA.
AC A0A1I9KNP0;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2017, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Vaa serine proteinase homolog 1 {ECO:0000303|PubMed:27327134, ECO:0000303|PubMed:30235482};
DE Short=VaaSPH-1 {ECO:0000303|PubMed:27327134, ECO:0000303|PubMed:30235482};
DE AltName: Full=Enzymatically inactive serine proteinase-like protein SPH-1 {ECO:0000312|EMBL:AMB36342.1};
DE AltName: Full=Snake venom serine protease homolog;
DE Flags: Precursor;
OS Vipera ammodytes ammodytes (Western sand viper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Vipera.
OX NCBI_TaxID=8705;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=27327134; DOI=10.1016/j.jprot.2016.06.020;
RA Latinovic Z., Leonardi A., Sribar J., Sajevic T., Zuzek M.C., Frangez R.,
RA Halassy B., Trampus-Bakija A., Pungercar J., Krizaj I.;
RT "Venomics of Vipera berus berus to explain differences in pathology
RT elicited by Vipera ammodytes ammodytes envenomation: therapeutic
RT implications.";
RL J. Proteomics 146:34-47(2016).
RN [2]
RP PROTEIN SEQUENCE OF 25-29, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, 3D-STRUCTURE MODELING IN COMPLEX WITH FVIIIA, AND
RP GLYCOSYLATION.
RC TISSUE=Venom;
RX PubMed=30235482; DOI=10.1055/s-0038-1669785;
RA Latinovic Z., Leonardi A., Kovacic L., Koh C.Y., Sribar J., Bakija A.T.,
RA Venkateswarlu D., Kini R.M., Krizaj I.;
RT "The first intrinsic tenase complex inhibitor with serine protease
RT structure offers a new perspective in anticoagulant therapy.";
RL Thromb. Haemost. 118:1713-1728(2018).
CC -!- FUNCTION: This is the first member of the serine protease family that
CC has strong anticoagulant activity and lacks enzymatic activity. It
CC inhibits activities of three blood coagulation complexes: (1)
CC prothrombinase complex (composed of blood coagulation factors Va and Xa
CC (F5 and F10)) (IC(50)=164.1 nM), (2) intrinsic tenase complex (composed
CC of factors VIIIa and IXa (F8 and F9)), and (3) extrinsic tenase complex
CC (composed of tissue factor and factor VIIa (F7)). The toxin has also
CC been observed to bind prothrombin, factor FVa, non-activated and
CC activated forms of factors FVII (F7) (FVII and FVIIa), factor FVIIIa
CC (F8), factors FIX and FIXa (F9) and factors FX and FXa (F10). The toxin
CC inhibits the activity of the intrinsic tenase complex mainly by
CC competing with FIXa (F9) for binding to FVIIIa (F8).
CC {ECO:0000269|PubMed:30235482}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30235482}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:27327134}.
CC -!- PTM: N-glycosylated. The toxin exists in multiple glycoforms.
CC {ECO:0000269|PubMed:30235482}.
CC -!- PHARMACEUTICAL: This first serine protease family member whose strong
CC anticoagulant activity is not proteolytic activity-dependent represents
CC an original molecular platform to develop innovative anticoagulant
CC substances by targeting FVIIIa. {ECO:0000305|PubMed:30235482}.
CC -!- MISCELLANEOUS: It does not hydrolysis fibrinogen, prothrombin, FIX, FX
CC and protein C (PubMed:30235482). It does not induce platelet
CC aggregation or agglutination (PubMed:30235482). It does not bind to
CC platelet phospholipids (PubMed:30235482). It does not bind to factor
CC FXI and FXIa, FXII and FXIIa, kallikrein and thrombin
CC (PubMed:30235482). {ECO:0000269|PubMed:30235482}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Lacks the canonical catalytic triad. Two of the three residues
CC necessary for catalytic activity are mutated. Arg-67 stands instead of
CC an His and at position Asn-206 stands instead of a Ser. As a result,
CC the protein is not proteolytically active.
CC {ECO:0000305|PubMed:30235482}.
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DR EMBL; KT148824; AMB36342.1; -; mRNA.
DR AlphaFoldDB; A0A1I9KNP0; -.
DR SMR; A0A1I9KNP0; -.
DR BRENDA; 3.4.21.74; 10997.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 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; Pharmaceutical;
KW Secreted; Serine protease homolog; Signal; Toxin.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..24
FT /evidence="ECO:0000305"
FT /id="PRO_0000445811"
FT CHAIN 25..260
FT /note="Vaa serine proteinase homolog 1"
FT /evidence="ECO:0000269|PubMed:30235482"
FT /id="PRO_5012045934"
FT DOMAIN 25..251
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 172..186
FT /note="Key residues for binding to FVIIIa"
FT /evidence="ECO:0000305|PubMed:30235482"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 52..68
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 100..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 144..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 176..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 202..227
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 260 AA; 28928 MW; D87ECAC91F3B2496 CRC64;
MVLIRVLANL LVLQLSYAQK SSELVIGGDE CNINEHPFLV ALHTARSKRF YCAGTLINQE
WVLTAARCDR KNIRIILGVH SKNVPNEDEQ MRVPKEKFFC LSSKTYTRWD KDIMLIRLKR
PVNDSTHIAP LSLPSSPPSV GSVCRIMGWG TITTTKVTYP DVPHCADINM FDYSVCQKVY
RKLPEKSRTL CAGILQGGID SCKVDNGGPL ICNGQIQGIV SWGGYPCAQP HKPALYTNVF
DYTDWIQSII AGNITATCPP
