VM2HS_GLOBR
ID VM2HS_GLOBR Reviewed; 317 AA.
AC Q90WC0; Q78CP2;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase brevilysin L4;
DE Short=SVMP;
DE AltName: Full=Snake venom metalloproteinase hxl-1;
DE EC=3.4.24.-;
DE Contains:
DE RecName: Full=Disintegrin salmosin-1;
DE AltName: Full=Platelet aggregation inhibitor;
DE Contains:
DE RecName: Full=Disintegrin salmosin-1 minor component;
DE AltName: Full=Disintegrin brevicaudin-2b;
DE Flags: Precursor; Fragment;
OS Gloydius brevicaudus (Korean slamosa snake) (Agkistrodon halys
OS brevicaudus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Gloydius.
OX NCBI_TaxID=259325;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Xilian H.;
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 213-317, PROTEIN SEQUENCE OF 245-317,
RP FUNCTION, SUBUNIT, AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=9722022; DOI=10.1016/s0049-3848(98)00053-x;
RA Kang I.-C., Chung K.-H., Lee S.-J., Yun Y., Moon H.-M., Kim D.-S.;
RT "Purification and molecular cloning of a platelet aggregation inhibitor
RT from the snake (Agkistrodon halys brevicaudus) venom.";
RL Thromb. Res. 91:65-73(1998).
RN [3]
RP PROTEIN SEQUENCE OF 247-317, AND FUNCTION.
RC TISSUE=Venom;
RA Oshikawa K., Yasukouchi Y., Terada S.;
RT "Isolation and primary structures of platelet aggregation inhibitors from
RT Gloydius halys brevicaudus venom.";
RL Fukuoka Univ. Sci. Rep. 30:201-208(2000).
RN [4]
RP FUNCTION.
RX PubMed=9856345;
RA Park D.-S., Kang I.-C., Kim H.-D., Chung K.-H., Kim D.-S., Yun Y.-D.;
RT "Cloning and characterization of novel disintegrins from Agkistrodon halys
RT venom.";
RL Mol. Cells 8:578-584(1998).
RN [5]
RP FUNCTION ON ANGIOGENESIS.
RX PubMed=10446992;
RA Kang I.-C., Lee Y.D., Kim D.-S.;
RT "A novel disintegrin salmosin inhibits tumor angiogenesis.";
RL Cancer Res. 59:3754-3760(1999).
RN [6]
RP FUNCTION ON MELANOMA CELL METASTASIS.
RX PubMed=10944460; DOI=10.1006/bbrc.2000.3130;
RA Kang I.-C., Kim D.-S., Jang Y., Chung K.-H.;
RT "Suppressive mechanism of salmosin, a novel disintegrin in B16 melanoma
RT cell metastasis.";
RL Biochem. Biophys. Res. Commun. 275:169-173(2000).
RN [7]
RP FUNCTION, AND BINDING TO ITGAV/ITGB3.
RX PubMed=12615062; DOI=10.1016/s0006-291x(03)00213-4;
RA Hong S.Y., Lee H., You W.K., Chung K.H., Kim D.S., Song K.;
RT "The snake venom disintegrin salmosin induces apoptosis by disassembly of
RT focal adhesions in bovine capillary endothelial cells.";
RL Biochem. Biophys. Res. Commun. 302:502-508(2003).
RN [8]
RP FUNCTION ON ANGIOGENESIS.
RX PubMed=14977354; DOI=10.3727/000000003772505353;
RA Kim S.I., Kim K.S., Kim H.S., Choi M.M., Kim D.-S., Chung K.-H., Park Y.S.;
RT "Inhibition of angiogenesis by salmosin expressed in vitro.";
RL Oncol. Res. 14:227-233(2004).
RN [9]
RP STRUCTURE BY NMR OF 245-317, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=14661951; DOI=10.1021/bi0300276;
RA Shin J., Hong S.-Y., Chung K.-H., Kang I.-C., Jang Y., Kim D.-S., Lee W.;
RT "Solution structure of a novel disintegrin, salmosin, from Agkistrondon
RT halys venom.";
RL Biochemistry 42:14408-14415(2003).
CC -!- FUNCTION: [Snake venom metalloproteinase brevilysin L4]:
CC metalloproteinase that impairs hemostasis in the envenomed animal.
CC {ECO:0000250, ECO:0000269|PubMed:10446992, ECO:0000269|PubMed:10944460,
CC ECO:0000269|PubMed:12615062, ECO:0000269|PubMed:14977354,
CC ECO:0000269|PubMed:9722022, ECO:0000269|PubMed:9856345,
CC ECO:0000269|Ref.3}.
CC -!- FUNCTION: [Disintegrin salmosin-1]: Inhibits GPIIb/GPIIIa
CC (ITGA2B/ITGB3) binding to immobilized fibrinogen with an IC(50) of 2.2
CC nM and ADP-induced platelet aggregation with an IC(50) of 131 nM,
CC respectively. Inhibits angiogenesis. By binding to vitronectin receptor
CC (alpha-V/beta-3 (ITGAV/ITGB3)), also induces apoptosis of endothelial
CC cells by blocking their attachment to extracellular matrix proteins.
CC -!- FUNCTION: [Disintegrin salmosin-1 minor component]: Inhibits platelet
CC aggregation induced by ADP (IC(50) is 30 nM), collagen (IC(50) is 500
CC nM), thrombin and epinephrin (IC(50) is 160 nM).
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:9722022}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: [Disintegrin salmosin-1]: Mass=7474; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9722022};
CC -!- MASS SPECTROMETRY: [Disintegrin salmosin-1 minor component]: Mass=7273;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:9722022};
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}.
CC -!- CAUTION: The metalloprotease is also encoded by another precursor (AC
CC Q698K8). {ECO:0000305}.
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DR EMBL; AF367868; AAK73517.1; -; mRNA.
DR EMBL; AF054626; AAC08997.1; -; mRNA.
DR PIR; A59409; A59409.
DR PDB; 1L3X; NMR; -; A=245-317.
DR PDBsum; 1L3X; -.
DR AlphaFoldDB; Q90WC0; -.
DR SMR; Q90WC0; -.
DR MEROPS; M12.326; -.
DR EvolutionaryTrace; Q90WC0; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell adhesion impairing toxin;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Hydrolase; Metal-binding; Metalloprotease;
KW Platelet aggregation inhibiting toxin; Protease; Secreted; Toxin; Zinc;
KW Zymogen.
FT PROPEP <1..26
FT /evidence="ECO:0000250"
FT /id="PRO_0000317493"
FT CHAIN 27..228
FT /note="Snake venom metalloproteinase brevilysin L4"
FT /id="PRO_0000317494"
FT PROPEP 229..244
FT /evidence="ECO:0000250"
FT /id="PRO_0000317495"
FT CHAIN 245..317
FT /note="Disintegrin salmosin-1"
FT /id="PRO_0000317496"
FT CHAIN 247..317
FT /note="Disintegrin salmosin-1 minor component"
FT /id="PRO_0000317497"
FT DOMAIN 32..228
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 236..317
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 295..297
FT /note="Cell attachment site"
FT ACT_SITE 169
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 35
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 119
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 143..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 183..207
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 185..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 250..259
FT /evidence="ECO:0000269|PubMed:14661951"
FT DISULFID 252..260
FT /evidence="ECO:0000269|PubMed:14661951"
FT DISULFID 265..279
FT /evidence="ECO:0000269|PubMed:14661951"
FT DISULFID 273..303
FT /evidence="ECO:0000269|PubMed:14661951"
FT DISULFID 278..282
FT /evidence="ECO:0000269|PubMed:14661951"
FT DISULFID 291..310
FT /evidence="ECO:0000269|PubMed:14661951"
FT NON_TER 1
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:1L3X"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:1L3X"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:1L3X"
SQ SEQUENCE 317 AA; 35110 MW; 9851177BCBE2202E CRC64;
EAPKMCGVTQ NWESYEPIKK ASQSNLTPAH QRYIELVIVA DHGMFTKYNG DSDKIREWVR
QMVNTVDEIY SYMYIDVALA GLEIWSNEDL INVQPAAPHT LDSFGKWRER DLLHRIHHDN
AMLLTAIDFD GPTIGLAYVG TMCKPKGSTG VVQDHSTINL RVAVTMAHEI GHNLGIHHDT
GSCSCGGYSC IMSPVISHEP SKYFSDCSYT QCWDFIMNQK PQCILNKPLR TDTVSTPVSG
NELLEAGEEC DCGSPGNPCC DAATCKLRQG AQCAEGLCCD QCRFMKEGTI CRRARGDDLD
DYCNGISAGC PRNPFHA
