VM2_GLOHA
ID VM2_GLOHA Reviewed; 73 AA.
AC Q9DGH6;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 25-MAY-2022, entry version 74.
DE RecName: Full=Disintegrin saxatilin;
OS Gloydius halys (Chinese water mocassin) (Agkistrodon halys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Gloydius.
OX NCBI_TaxID=8714;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND MASS SPECTROMETRY.
RC TISSUE=Venom gland;
RX PubMed=11864711; DOI=10.1016/s0049-3848(01)00416-9;
RA Hong S.-Y., Koh Y.-S., Chung K.-H., Kim D.-S.;
RT "Snake venom disintegrin, saxatilin, inhibits platelet aggregation, human
RT umbilical vein endothelial cell proliferation, and smooth muscle cell
RT migration.";
RL Thromb. Res. 105:79-86(2002).
RN [2]
RP DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=12054633; DOI=10.1016/s0006-291x(02)00258-9;
RA Hong S.-Y., Sohn Y.-D., Chung K.-H., Kim D.-S.;
RT "Structural and functional significance of disulfide bonds in saxatilin, a
RT 7.7 kDa disintegrin.";
RL Biochem. Biophys. Res. Commun. 293:530-536(2002).
RN [3]
RP FUNCTION.
RX PubMed=16410825; DOI=10.1038/sj.cgt.7700924;
RA Kim K.S., Kim D.-S., Chung K.-H., Park Y.S.;
RT "Inhibition of angiogenesis and tumor progression by hydrodynamic
RT cotransfection of angiostatin K1-3, endostatin, and saxatilin genes.";
RL Cancer Gene Ther. 13:563-571(2006).
RN [4]
RP FUNCTION.
RX PubMed=17394781; DOI=10.5483/bmbrep.2007.40.2.290;
RA Kim D.S., Jang Y.J., Jeon O.H., Kim D.-S.;
RT "Saxatilin, a snake venom disintegrin, suppresses TNF-alpha-induced ovarian
RT cancer cell invasion.";
RL J. Biochem. Mol. Biol. 40:290-294(2007).
RN [5]
RP FUNCTION.
RX PubMed=17562297; DOI=10.5483/bmbrep.2007.40.3.439;
RA Jang Y.J., Kim D.S., Jeon O.H., Kim D.-S.;
RT "Saxatilin suppresses tumor-induced angiogenesis by regulating VEGF
RT expression in NCI-H460 human lung cancer cells.";
RL J. Biochem. Mol. Biol. 40:439-443(2007).
RN [6]
RP FUNCTION.
RX PubMed=17215584; DOI=10.1159/000098519;
RA Jang Y.J., Jeon O.H., Kim D.-S.;
RT "Saxatilin, a snake venom disintegrin, regulates platelet activation
RT associated with human vascular endothelial cell migration and invasion.";
RL J. Vasc. Res. 44:129-137(2007).
RN [7]
RP FUNCTION.
RX PubMed=16806476; DOI=10.1016/j.molimm.2006.05.001;
RA Kim D.S., Jang Y.J., Jeon O.H., Kim D.-S.;
RT "Saxatilin inhibits TNF-alpha-induced proliferation by suppressing AP-1-
RT dependent IL-8 expression in the ovarian cancer cell line MDAH 2774.";
RL Mol. Immunol. 44:1409-1416(2007).
RN [8]
RP TOXIC DOSE.
RC TISSUE=Venom gland;
RX PubMed=18155118; DOI=10.1016/j.toxicon.2007.10.019;
RA Sohn Y.-D., Hong S.-Y., Cho K.-S., Choi W.-S., Song S.-W., Bae J.-S.,
RA Kim D.-S., Chung K.-H.;
RT "Acute and repeated dose toxicity studies of recombinant saxatilin, a
RT disintegrin from the Korean snake (Gloydius saxatilis).";
RL Toxicon 51:406-417(2008).
CC -!- FUNCTION: Inhibits fibrinogen interaction with platelets by binding to
CC alpha-IIb/beta-3 (ITGA2B/ITGB3). Also inhibits ADP-induced platelet
CC aggregation. Inhibits basic fibroblast growth factor (bFGF)-induced
CC proliferation of human vascular endothelial cell (HUVEC), and
CC vitronectin-induced migration of smooth muscle cells (SMC). It also
CC regulates platelet activation associated with HUVEC migration and
CC invasion, suppresses TNF-alpha-induced ovarian cancer cell
CC proliferation and invasion, and inhibits angiogenesis and tumor
CC progression. {ECO:0000269|PubMed:11864711, ECO:0000269|PubMed:16410825,
CC ECO:0000269|PubMed:16806476, ECO:0000269|PubMed:17215584,
CC ECO:0000269|PubMed:17394781, ECO:0000269|PubMed:17562297}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11864711}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: Mass=7712; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11864711};
CC -!- TOXIC DOSE: LD(50) is 400 mg/kg body weight in male mice and 600 mg/kg
CC in female mice (intravenous). From the autopsies of test mice, hepatic
CC congestion is found in dead mice, but the organs of surviving mice
CC lacked any other abnormal indications. {ECO:0000269|PubMed:18155118}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the medium disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIa sub-subfamily. {ECO:0000305}.
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DR EMBL; AY005480; AAG01882.1; -; mRNA.
DR AlphaFoldDB; Q9DGH6; -.
DR SMR; Q9DGH6; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR Pfam; PF00200; Disintegrin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Cell adhesion impairing toxin; Developmental protein;
KW Differentiation; Disulfide bond; Hemostasis impairing toxin;
KW Platelet aggregation inhibiting toxin; Secreted; Toxin.
FT CHAIN 1..73
FT /note="Disintegrin saxatilin"
FT /id="PRO_0000318181"
FT DOMAIN 1..73
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 51..53
FT /note="Cell attachment site"
FT DISULFID 6..15
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000269|PubMed:12054633"
FT DISULFID 8..16
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000269|PubMed:12054633"
FT DISULFID 21..35
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000269|PubMed:12054633"
FT DISULFID 29..59
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000269|PubMed:12054633"
FT DISULFID 34..38
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000269|PubMed:12054633"
FT DISULFID 47..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000269|PubMed:12054633"
SQ SEQUENCE 73 AA; 7726 MW; 8F0225BBD5502FE7 CRC64;
EAGEECDCGA PANPCCDAAT CKLRPGAQCA EGLCCDQCRF MKEGTICRMA RGDDMDDYCN
GISAGCPRNP FHA
