VKT_OXYSC
ID VKT_OXYSC Reviewed; 88 AA.
AC B7S4N9; B5L5M8; B7S4N8; Q7LZE4;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 25-MAY-2022, entry version 46.
DE RecName: Full=Kunitz-type serine protease inhibitor taicotoxin;
DE AltName: Full=Taicatoxin, serine protease inhibitor component;
DE Short=TCX;
DE Short=TSPI;
DE AltName: Full=Venom protease inhibitor 1;
DE AltName: Full=Venom protease inhibitor 2;
DE Flags: Precursor;
OS Oxyuranus scutellatus scutellatus (Australian taipan) (Coastal taipan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Acanthophiinae; Oxyuranus.
OX NCBI_TaxID=8667;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Earl S.T., Flight S., Liao A., Masci P.P., de Jersey J., Lavin M.F.;
RT "Characterization of a serine protease inhibitor from Oxyuranus scutellatus
RT venom.";
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Venom gland;
RX PubMed=18979207; DOI=10.1007/s00018-008-8573-5;
RA St Pierre L., Earl S.T., Filippovich I., Sorokina N., Masci P.P.,
RA De Jersey J., Lavin M.F.;
RT "Common evolution of waprin and Kunitz-like toxin families in Australian
RT venomous snakes.";
RL Cell. Mol. Life Sci. 65:4039-4054(2008).
RN [3]
RP PROTEIN SEQUENCE OF 25-86, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=1485334; DOI=10.1016/0041-0101(92)90511-3;
RA Possani L.D., Martin B.M., Yatani A., Mochca-Morales J., Zamudio F.Z.,
RA Gurrola G.B., Brown A.M.;
RT "Isolation and physiological characterization of taicatoxin, a complex
RT toxin with specific effects on calcium channels.";
RL Toxicon 30:1343-1364(1992).
RN [4]
RP PROTEIN SEQUENCE OF 25-36, FUNCTION OF THE MONOMER, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=21843588; DOI=10.1016/j.biochi.2011.08.003;
RA Earl S.T., Richards R., Johnson L.A., Flight S., Anderson S., Liao A.,
RA de Jersey J., Masci P.P., Lavin M.F.;
RT "Identification and characterisation of Kunitz-type plasma kallikrein
RT inhibitors unique to Oxyuranus sp. snake venoms.";
RL Biochimie 94:365-373(2012).
RN [5]
RP FUNCTION.
RX PubMed=8901456; DOI=10.1007/bf00240032;
RA Fantini E., Athias P., Tirosh R., Pinson A.;
RT "Effect of TaiCatoxin (TCX) on the electrophysiological, mechanical and
RT biochemical characteristics of spontaneously beating ventricular
RT cardiomyocytes.";
RL Mol. Cell. Biochem. 160:61-66(1996).
RN [6]
RP FUNCTION.
RX PubMed=9242659; DOI=10.1074/jbc.272.32.19925;
RA Doorty K.B., Bevan S., Wadsworth J.D.F., Strong P.N.;
RT "A novel small conductance Ca2+-activated K+ channel blocker from Oxyuranus
RT scutellatus taipan venom. Re-evaluation of taicatoxin as a selective Ca2+
RT channel probe.";
RL J. Biol. Chem. 272:19925-19930(1997).
RN [7]
RP FUNCTION.
RX PubMed=15855042; DOI=10.1016/j.heares.2004.12.003;
RA Su M.-C., Lee S.-Y., Tan C.-T., Su C.-C., Li S.-Y., Lin R.-H., Hung C.-C.,
RA Lin M.-J.;
RT "Taicatoxin inhibits the calcium-dependent slow motility of mammalian outer
RT hair cells.";
RL Hear. Res. 203:172-179(2005).
CC -!- FUNCTION: Heterotrimer: blocks the voltage-dependent L-type calcium
CC channels (Cav) from the heart, and the small conductance calcium-
CC activated potassium channels (KCa) in the chromaffin cells and in the
CC brain. Is very toxic to mice.
CC -!- FUNCTION: Monomer: serine protease inhibitor that inhibits plasma
CC kallikrein (Ki=0.057 nM), tissue kallikrein (Ki=0.23 nM), trypsin
CC (Ki=0.31 nM), plasmin (Ki=6.1 nM), elastase (Ki=201 nM), factor Xa
CC (Ki=871 nM), alpha-factor XIIa (Ki=2380 nM). Does not inhibit APC,
CC urokinase-type plasminogen activator (uPA/PLAU), tissue plasminogen
CC activator (tPA/PLAT), thrombin and factor VIIa. In addition, the
CC monomer inhibits fibrinolysis in whole blood and prolonged the
CC intrinsec clotting time.
CC -!- SUBUNIT: Heterotrimer composed of an alpha-neurotoxin-like peptide of 8
CC kDa (AC P0CJ35), a neurotoxic phospholipase of 16 kDa (AC Q7LZG2) and
CC this serine protease inhibitor of 7 kDa at an approximate stoichiometry
CC of 1:1:4; non-covalently linked. {ECO:0000269|PubMed:1485334}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1485334}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:1485334}.
CC -!- TOXIC DOSE: LD(50) of the heterotrimer is 50-100 ug/kg to mice.
CC {ECO:0000269|PubMed:1485334}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Taicatoxin entry;
CC URL="https://en.wikipedia.org/wiki/Taicatoxin";
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DR EMBL; EF112394; ABO31438.1; -; mRNA.
DR EMBL; EF112393; ABO31437.1; -; mRNA.
DR EMBL; EU401816; ACC77765.1; -; Genomic_DNA.
DR PIR; A44180; A44180.
DR AlphaFoldDB; B7S4N9; -.
DR SMR; B7S4N9; -.
DR MEROPS; I02.062; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd00109; KU; 1.
DR Gene3D; 4.10.410.10; -; 1.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR Pfam; PF00014; Kunitz_BPTI; 1.
DR PRINTS; PR00759; BASICPTASE.
DR SMART; SM00131; KU; 1.
DR SUPFAM; SSF57362; SSF57362; 1.
DR PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE 1: Evidence at protein level;
KW Blood coagulation cascade inhibiting toxin;
KW Calcium channel impairing toxin;
KW Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Protease inhibitor; Secreted; Serine protease inhibitor; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:1485334,
FT ECO:0000269|PubMed:21843588"
FT CHAIN 25..86
FT /note="Kunitz-type serine protease inhibitor taicotoxin"
FT /id="PRO_0000155443"
FT PROPEP 87..88
FT /id="PRO_0000376929"
FT DOMAIN 31..81
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 41..42
FT /note="Reactive bond for trypsin"
FT /evidence="ECO:0000250"
FT DISULFID 31..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 40..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 56..77
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT CONFLICT 17..18
FT /note="EV -> AE (in Ref. 2; ACC77765)"
FT /evidence="ECO:0000305"
FT CONFLICT 24..25
FT /note="SK -> GQ (in Ref. 2; ACC77765)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="K -> Q (in Ref. 2; ACC77765)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="K -> N (in Ref. 2; ACC77765 and 1; ABO31437)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="S -> K (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 88 AA; 9711 MW; BA22F6D73E1D6F38 CRC64;
MSSGGLLLLL GLLTLWEVLT PVSSKDRPKF CHLPPKPGPC RAAIPRFYYN PHSKQCEKFI
YGGCHGNANS FKTPDECNYT CLGVSLPK
