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VKT1_PSETT
ID   VKT1_PSETT              Reviewed;          83 AA.
AC   Q90WA1;
DT   16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   25-MAY-2022, entry version 69.
DE   RecName: Full=Kunitz-type serine protease inhibitor textilinin-1;
DE            Short=Txln-1;
DE   Flags: Precursor;
OS   Pseudonaja textilis textilis (Eastern brown snake).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Acanthophiinae; Pseudonaja.
OX   NCBI_TaxID=169397;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC   TISSUE=Venom gland;
RX   PubMed=12406072; DOI=10.1046/j.1365-2141.2002.03878.x;
RA   Filippovich I., Sorokina N., Masci P.P., de Jersey J., Whitaker A.N.,
RA   Winzor D.J., Gaffney P.J., Lavin M.F.;
RT   "A family of textilinin genes, two of which encode proteins with
RT   antihaemorrhagic properties.";
RL   Br. J. Haematol. 119:376-384(2002).
RN   [2]
RP   PROTEIN SEQUENCE OF 25-83, FUNCTION, AND MASS SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=10847427; DOI=10.1097/00001721-200006000-00011;
RA   Masci P.P., Whitaker A.N., Sparrow L.G., de Jersey J., Winzor D.J.,
RA   Watters D.J., Lavin M.F., Gaffney P.J.;
RT   "Textilinins from Pseudonaja textilis textilis. Characterization of two
RT   plasmin inhibitors that reduce bleeding in an animal model.";
RL   Blood Coagul. Fibrinolysis 11:385-393(2000).
RN   [3]
RP   FUNCTION.
RX   PubMed=16707925; DOI=10.1159/000092421;
RA   Flight S., Johnson L., Trabi M., Gaffney P., Lavin M., de Jersey J.,
RA   Masci P.;
RT   "Comparison of textilinin-1 with aprotinin as serine protease inhibitors
RT   and as antifibrinolytic agents.";
RL   Pathophysiol. Haemost. Thromb. 34:188-193(2005).
RN   [4]
RP   FUNCTION.
RX   PubMed=19236611; DOI=10.1111/j.1365-2141.2009.07605.x;
RA   Flight S.M., Johnson L.A., Du Q.S., Warner R.L., Trabi M., Gaffney P.J.,
RA   Lavin M.F., de Jersey J., Masci P.P.;
RT   "Textilinin-1, an alternative anti-bleeding agent to aprotinin: importance
RT   of plasmin inhibition in controlling blood loss.";
RL   Br. J. Haematol. 145:207-211(2009).
RN   [5]
RP   FUNCTION.
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   [6]
RP   PHARMACEUTICAL.
RX   PubMed=21184772; DOI=10.1016/j.toxicon.2010.12.010;
RA   Earl S.T., Masci P.P., de Jersey J., Lavin M.F., Dixon J.;
RT   "Drug development from Australian elapid snake venoms and the Venomics
RT   pipeline of candidates for haemostasis: Textilinin-1 (Q8008), Haempatch
RT   (Q8009) and CoVase (V0801).";
RL   Toxicon 59:456-463(2012).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=16284125; DOI=10.1074/mcp.m500270-mcp200;
RA   Birrell G.W., Earl S., Masci P.P., de Jersey J., Wallis T.P., Gorman J.J.,
RA   Lavin M.F.;
RT   "Molecular diversity in venom from the Australian Brown snake, Pseudonaja
RT   textilis.";
RL   Mol. Cell. Proteomics 5:379-389(2006).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), AND DISULFIDE BONDS.
RX   PubMed=16820682; DOI=10.1107/s1744309106019099;
RA   Millers E.-K.I., Masci P.P., Lavin M.F., de Jersey J., Guddat L.W.;
RT   "Crystallization and preliminary X-ray analysis of a Kunitz-type inhibitor,
RT   textilinin-1 from Pseudonaja textilis textilis.";
RL   Acta Crystallogr. F 62:642-645(2006).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 25-83, AND DISULFIDE BONDS.
RX   PubMed=19490116; DOI=10.1111/j.1742-4658.2009.07034.x;
RA   Millers E.K., Trabi M., Masci P.P., Lavin M.F., de Jersey J., Guddat L.W.;
RT   "Crystal structure of textilinin-1, a Kunitz-type serine protease inhibitor
RT   from the venom of the Australian common brown snake (Pseudonaja
RT   textilis).";
RL   FEBS J. 276:3163-3175(2009).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 25-83 IN COMPLEXES WITH THE
RP   PROTEASE DOMAIN OF HUMAN PLASMIN AND WITH TRYPSIN, FUNCTION, AND DISULFIDE
RP   BONDS.
RX   PubMed=23335990; DOI=10.1371/journal.pone.0054104;
RA   Millers E.K., Johnson L.A., Birrell G.W., Masci P.P., Lavin M.F.,
RA   de Jersey J., Guddat L.W.;
RT   "The structure of human microplasmin in complex with textilinin-1, an
RT   aprotinin-like inhibitor from the Australian brown snake.";
RL   PLoS ONE 8:E54104-E54104(2013).
CC   -!- FUNCTION: Strongly inhibits plasmin (Ki=0.44 nM) and trypsin (Ki=0.42
CC       nM). Has little effect on plasma (Ki=1870 nM) and tissue (Ki=12900 nM)
CC       kallikreins. In vivo, reduces bleeding in a small animal model.
CC       {ECO:0000269|PubMed:10847427, ECO:0000269|PubMed:12406072,
CC       ECO:0000269|PubMed:16707925, ECO:0000269|PubMed:19236611,
CC       ECO:0000269|PubMed:21843588, ECO:0000269|PubMed:23335990}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- MASS SPECTROMETRY: Mass=6689.3; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:10847427};
CC   -!- PHARMACEUTICAL: Is under preclinical trial by the Australian
CC       biopharmaceutical company QRxPharma Ltd, its subsidiary Venomics Pty
CC       Ltd (VPL) and the University of Queensland (UQ) under the name
CC       textilinin-1 (Q8008). Tested as a potent and selective plasmin
CC       inhibitor that has application as an anti-fibrinolytic agent to reduce
CC       blood loss associated with complex surgeries. It is being investigated
CC       as an alternative treatment to aprotinin (Trasylol).
CC   -!- MISCELLANEOUS: Has no effect on tissue plasminogen inhibitor
CC       (tPA/PLAT), urokinase, activated protein C (APC), elastase, factor Xa,
CC       alpha-factor XIIa, thrombin, and factor VIIa.
CC       {ECO:0000305|PubMed:21843588}.
CC   -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
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DR   EMBL; AF402324; AAK95519.1; -; mRNA.
DR   PDB; 3BYB; X-ray; 1.63 A; A/B/C=25-83.
DR   PDB; 3D65; X-ray; 1.64 A; I=27-83.
DR   PDB; 3UIR; X-ray; 2.78 A; C/D=25-83.
DR   PDB; 5ZJ3; X-ray; 1.88 A; A/B/C=25-83.
DR   PDBsum; 3BYB; -.
DR   PDBsum; 3D65; -.
DR   PDBsum; 3UIR; -.
DR   PDBsum; 5ZJ3; -.
DR   AlphaFoldDB; Q90WA1; -.
DR   SMR; Q90WA1; -.
DR   MEROPS; I02.052; -.
DR   EvolutionaryTrace; Q90WA1; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:CACAO.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0035899; P:negative regulation of blood coagulation in another organism; IDA:CACAO.
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   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Hemostasis impairing toxin; Pharmaceutical; Protease inhibitor; Secreted;
KW   Serine protease inhibitor; Signal; Toxin.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000269|PubMed:10847427"
FT   CHAIN           25..83
FT                   /note="Kunitz-type serine protease inhibitor textilinin-1"
FT                   /id="PRO_0000376901"
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   DISULFID        40..64
FT   DISULFID        56..77
FT   HELIX           29..32
FT                   /evidence="ECO:0007829|PDB:3BYB"
FT   STRAND          44..50
FT                   /evidence="ECO:0007829|PDB:3BYB"
FT   TURN            51..54
FT                   /evidence="ECO:0007829|PDB:3BYB"
FT   STRAND          55..61
FT                   /evidence="ECO:0007829|PDB:3BYB"
FT   STRAND          63..65
FT                   /evidence="ECO:0007829|PDB:3D65"
FT   STRAND          71..73
FT                   /evidence="ECO:0007829|PDB:3BYB"
FT   HELIX           74..81
FT                   /evidence="ECO:0007829|PDB:3BYB"
SQ   SEQUENCE   83 AA;  9173 MW;  2045E50657014221 CRC64;
     MSSGGLLLLL GLLTLWEVLT PVSSKDRPDF CELPADTGPC RVRFPSFYYN PDEKKCLEFI
     YGGCEGNANN FITKEECEST CAA
 
 
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