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B7S4N9

- VKT_OXYSC

UniProt

B7S4N9 - VKT_OXYSC

Protein

Kunitz-type serine protease inhibitor taicotoxin

Gene
N/A
Organism
Oxyuranus scutellatus scutellatus (Australian taipan) (Coastal taipan)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Heterotrimer: blocks the voltage-dependent L-type calcium channels (Cav) from the heart, and the small conductance calcium-activated potassium channels (KCa) in the chromaffin cells and in the brain. Is very toxic to mice.
    Monomer: serine protease inhibitor that inhibits plasma kallikrein (Ki=0.057 nM), tissue kallikrein (Ki=0.23 nM), trypsin (Ki=0.31 nM), plasmin (Ki=6.1 nM), elastase (Ki=201 nM), factor Xa (Ki=871 nM), alpha-factor XIIa (Ki=2380 nM). Does not inhibit APC, urokinase-type plasminogen activator (uPA/PLAU), tissue plasminogen activator (tPA/PLAT), thrombin and factor VIIa. In addition, the monomer inhibits fibrinolysis in whole blood and prolonged the intrinsec clotting time.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei41 – 422Reactive bond for trypsinBy similarity

    GO - Molecular functioni

    1. serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

    Keywords - Molecular functioni

    Blood coagulation cascade inhibiting toxin, Calcium channel impairing toxin, Calcium-activated potassium channel impairing toxin, Hemostasis impairing toxin, Ion channel impairing toxin, Neurotoxin, Potassium channel impairing toxin, Protease inhibitor, Serine protease inhibitor, Toxin, Voltage-gated calcium channel impairing toxin

    Protein family/group databases

    MEROPSiI02.062.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Kunitz-type serine protease inhibitor taicotoxin
    Alternative name(s):
    Taicatoxin, serine protease inhibitor component
    Short name:
    TCX
    Short name:
    TSPI
    Venom protease inhibitor 1
    Venom protease inhibitor 2
    OrganismiOxyuranus scutellatus scutellatus (Australian taipan) (Coastal taipan)
    Taxonomic identifieri8667 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeAcanthophiinaeOxyuranus

    Subcellular locationi

    Secreted 1 Publication

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Toxic dosei

    LD50 of the heterotrimer is 50-100 µg/kg to mice.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 24242 PublicationsAdd
    BLAST
    Chaini25 – 8662Kunitz-type serine protease inhibitor taicotoxinPRO_0000155443Add
    BLAST
    Propeptidei87 – 882PRO_0000376929

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi31 ↔ 81PROSITE-ProRule annotation
    Disulfide bondi40 ↔ 64PROSITE-ProRule annotation
    Disulfide bondi56 ↔ 77PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond

    Expressioni

    Tissue specificityi

    Expressed by the venom gland.1 Publication

    Interactioni

    Subunit structurei

    Heterotrimer composed of an alpha-neurotoxin-like peptide of 8 kDa (AC P0CJ35), a neurotoxic phospholipase of 16 kDa (AC Q7LZG2) and this serine protease inhibitor of 7 kDa at an approximate stoichiometry of 1:1:4; non-covalently linked.1 Publication

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini31 – 8151BPTI/Kunitz inhibitorPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the venom Kunitz-type family.Curated
    Contains 1 BPTI/Kunitz inhibitor domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    HOVERGENiHBG006193.

    Family and domain databases

    Gene3Di4.10.410.10. 1 hit.
    InterProiIPR002223. Prot_inh_Kunz-m.
    IPR020901. Prtase_inh_Kunz-CS.
    [Graphical view]
    PfamiPF00014. Kunitz_BPTI. 1 hit.
    [Graphical view]
    PRINTSiPR00759. BASICPTASE.
    SMARTiSM00131. KU. 1 hit.
    [Graphical view]
    SUPFAMiSSF57362. SSF57362. 1 hit.
    PROSITEiPS00280. BPTI_KUNITZ_1. 1 hit.
    PS50279. BPTI_KUNITZ_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    B7S4N9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSSGGLLLLL GLLTLWEVLT PVSSKDRPKF CHLPPKPGPC RAAIPRFYYN   50
    PHSKQCEKFI YGGCHGNANS FKTPDECNYT CLGVSLPK 88
    Length:88
    Mass (Da):9,711
    Last modified:February 10, 2009 - v1
    Checksum:iBA22F6D73E1D6F38
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti17 – 182EV → AE in ACC77765. (PubMed:18979207)Curated
    Sequence conflicti24 – 252SK → GQ in ACC77765. (PubMed:18979207)Curated
    Sequence conflicti25 – 251K → Q in ACC77765. (PubMed:18979207)Curated
    Sequence conflicti36 – 361K → N in ACC77765. (PubMed:18979207)Curated
    Sequence conflicti36 – 361K → N in ABO31437. 1 PublicationCurated
    Sequence conflicti70 – 701S → K AA sequence (PubMed:1485334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    EF112394 mRNA. Translation: ABO31438.1.
    EF112393 mRNA. Translation: ABO31437.1.
    EU401816 Genomic DNA. Translation: ACC77765.1.
    PIRiA44180.

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Taicatoxin entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    EF112394 mRNA. Translation: ABO31438.1 .
    EF112393 mRNA. Translation: ABO31437.1 .
    EU401816 Genomic DNA. Translation: ACC77765.1 .
    PIRi A44180.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi I02.062.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    HOVERGENi HBG006193.

    Family and domain databases

    Gene3Di 4.10.410.10. 1 hit.
    InterProi IPR002223. Prot_inh_Kunz-m.
    IPR020901. Prtase_inh_Kunz-CS.
    [Graphical view ]
    Pfami PF00014. Kunitz_BPTI. 1 hit.
    [Graphical view ]
    PRINTSi PR00759. BASICPTASE.
    SMARTi SM00131. KU. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57362. SSF57362. 1 hit.
    PROSITEi PS00280. BPTI_KUNITZ_1. 1 hit.
    PS50279. BPTI_KUNITZ_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of a serine protease inhibitor from Oxyuranus scutellatus venom."
      Earl S.T., Flight S., Liao A., Masci P.P., de Jersey J., Lavin M.F.
      Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Venom gland.
    2. "Common evolution of waprin and Kunitz-like toxin families in Australian venomous snakes."
      St Pierre L., Earl S.T., Filippovich I., Sorokina N., Masci P.P., De Jersey J., Lavin M.F.
      Cell. Mol. Life Sci. 65:4039-4054(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Venom gland.
    3. "Isolation and physiological characterization of taicatoxin, a complex toxin with specific effects on calcium channels."
      Possani L.D., Martin B.M., Yatani A., Mochca-Morales J., Zamudio F.Z., Gurrola G.B., Brown A.M.
      Toxicon 30:1343-1364(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 25-86, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, LETHAL DOSE.
      Tissue: Venom.
    4. "Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms."
      Earl S.T., Richards R., Johnson L.A., Flight S., Anderson S., Liao A., de Jersey J., Masci P.P., Lavin M.F.
      Biochimie 94:365-373(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 25-36, FUNCTION OF THE MONOMER, IDENTIFICATION BY MASS SPECTROMETRY.
    5. "Effect of TaiCatoxin (TCX) on the electrophysiological, mechanical and biochemical characteristics of spontaneously beating ventricular cardiomyocytes."
      Fantini E., Athias P., Tirosh R., Pinson A.
      Mol. Cell. Biochem. 160:61-66(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "A novel small conductance Ca2+-activated K+ channel blocker from Oxyuranus scutellatus taipan venom. Re-evaluation of taicatoxin as a selective Ca2+ channel probe."
      Doorty K.B., Bevan S., Wadsworth J.D.F., Strong P.N.
      J. Biol. Chem. 272:19925-19930(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Taicatoxin inhibits the calcium-dependent slow motility of mammalian outer hair cells."
      Su M.-C., Lee S.-Y., Tan C.-T., Su C.-C., Li S.-Y., Lin R.-H., Hung C.-C., Lin M.-J.
      Hear. Res. 203:172-179(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiVKT_OXYSC
    AccessioniPrimary (citable) accession number: B7S4N9
    Secondary accession number(s): B5L5M8, B7S4N8, Q7LZE4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 16, 2009
    Last sequence update: February 10, 2009
    Last modified: October 1, 2014
    This is version 30 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programAnimal Toxin Annotation Program
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Direct protein sequencing

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3