VM2B1_AGKBI
ID VM2B1_AGKBI Reviewed; 291 AA.
AC P0C6E3;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Zinc metalloproteinase-disintegrin bilitoxin-1;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Contains:
DE RecName: Full=Disintegrin;
OS Agkistrodon bilineatus (Cantil) (Tropical moccasin).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX NCBI_TaxID=8718;
RN [1]
RP PROTEIN SEQUENCE, SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY,
RP GLYCOSYLATION AT ASN-89; ASN-155 AND ASN-181, PYROGLUTAMATE FORMATION AT
RP GLN-1, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom;
RX PubMed=10871038; DOI=10.1006/abbi.2000.1795;
RA Nikai T., Taniguchi K., Komori Y., Masuda K., Fox J.W., Sugihara H.;
RT "Primary structure and functional characterization of bilitoxin-1, a novel
RT dimeric P-II snake venom metalloproteinase from Agkistrodon bilineatus
RT venom.";
RL Arch. Biochem. Biophys. 378:6-15(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=2676645; DOI=10.1016/0020-711x(89)90388-1;
RA Imai K., Nikai T., Sugihara H., Ownby C.L.;
RT "Hemorrhagic toxin from the venom of Agkistrodon bilineatus (common
RT cantil).";
RL Int. J. Biochem. 21:667-673(1989).
RN [3]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=2219144; DOI=10.1016/s0041-0101(09)80006-8;
RA Ownby C.L., Nika T., Imai K., Sugihara H.;
RT "Pathogenesis of hemorrhage induced by bilitoxin, a hemorrhagic toxin
RT isolated from the venom of the common cantil (Agkistrodon bilineatus
RT bilineatus).";
RL Toxicon 28:837-846(1990).
CC -!- FUNCTION: This hemorrhagic toxin hydrolyzes the Aalpha-chain (FGA) and
CC more slowly the Bbeta-chain (FGB) of fibrin and fibrinogen. Also
CC hydrolyzes casein. It lacks platelet aggregation inhibitory activity.
CC After intramuscular injection, it acts rapidly to disrupt the capillary
CC endothelium without damaging the intercellular junctions, and also
CC appears to damage skeletal muscle cells. Cleaves insulin B chain at
CC '27-Asn-|-Gln-28', '34-His-|-Leu-35', '38-Ala-|-Leu-39', '40-Tyr-|-Leu-
CC 41', '46-Arg-|-Gly-47' and '48-Phe-|-Phe-49' bonds (PubMed:2676645).
CC {ECO:0000269|PubMed:2219144, ECO:0000269|PubMed:2676645}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and EGTA, but not by cysteine or
CC soybean trypsin inhibitor (SBTI). {ECO:0000269|PubMed:2676645}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:10871038}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: Glycosylated; glycans contain fucose, galactosamine, glucosamine,
CC galactose, and mannose. Sialylated; 75% of the hemorrhagic activity of
CC native bilitoxin-1 is lost upon removal of the sialic acid moieties of
CC bilitoxin-1. {ECO:0000269|PubMed:10871038}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the long disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIc sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: This protein does not undergo proteolytic processing to
CC release the disintegrin domain. However, in experimental conditions
CC (absence of calcium), the disintegrin domain is autoproteolytically
CC processed from the mature protein and give the chain 208-291.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; P0C6E3; -.
DR SMR; P0C6E3; -.
DR iPTMnet; P0C6E3; -.
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 Calcium; Direct protein sequencing; Disulfide bond; Fibrinogenolytic toxin;
KW Fibrinolytic toxin; Glycoprotein; Hemorrhagic toxin;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Myotoxin; Protease; Pyrrolidone carboxylic acid; Secreted; Sialic acid;
KW Toxin; Zinc.
FT CHAIN 1..291
FT /note="Zinc metalloproteinase-disintegrin bilitoxin-1"
FT /id="PRO_0000321885"
FT CHAIN 208..291
FT /note="Disintegrin"
FT /id="PRO_0000424723"
FT DOMAIN 7..203
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 211..291
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 273..275
FT /note="Cell attachment site; atypical (MGD)"
FT ACT_SITE 144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 10
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 216
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 220
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:10871038"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10871038"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10871038"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10871038"
FT DISULFID 61
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT DISULFID 118..198
FT /evidence="ECO:0000250"
FT DISULFID 158..182
FT /evidence="ECO:0000250"
FT DISULFID 160..165
FT /evidence="ECO:0000250"
FT DISULFID 214..233
FT /evidence="ECO:0000255"
FT DISULFID 225..243
FT /evidence="ECO:0000250"
FT DISULFID 227..238
FT /evidence="ECO:0000250"
FT DISULFID 229
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT DISULFID 237..260
FT /evidence="ECO:0000250"
FT DISULFID 251..257
FT /evidence="ECO:0000250"
FT DISULFID 256..281
FT /evidence="ECO:0000250"
FT DISULFID 269..288
FT /evidence="ECO:0000250"
SQ SEQUENCE 291 AA; 32314 MW; 97048A61775660B0 CRC64;
QRYNPYKYIE LFLVVDNRMV TKYNGDLDKI KTRIYELVNI LNEIYRPLYI RVALVGIEFW
CNKDLINVKS ASSVTLASFA NWRESVLPNR TSHDNAQLLT AIVFNRGVIG SAYPAGMCDP
NRSVGTVQDH SEINLQVAIT MAHEIGHNLG MGHDNNSCTC GGYSCIMLPA LSDQPSKYFS
NCSYIQYRDF IMNQDPQCIL NEPSGTDIVS PPVCGNDILE VGEECDCGCP RNCQDPCCNA
ATCKKYSWVQ CESGECCDQC RFKGAGTECR RAMGDDPGGR CTGQSADCPR N
