VM2IA_BOTIN
ID VM2IA_BOTIN Reviewed; 476 AA.
AC Q5XUW8;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase insularinase-A;
DE Short=SVMP;
DE EC=3.4.24.-;
DE Contains:
DE RecName: Full=Disintegrin insularin {ECO:0000303|PubMed:21073888};
DE Flags: Precursor;
OS Bothrops insularis (Golden lancehead) (Lachesis insularis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8723;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 195-212; 325-338; 354-362
RP AND 364-386, FUNCTION OF THE METALLOPROTEINASE, ACTIVITY REGULATION,
RP SUBUNIT, AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=16006246; DOI=10.1515/bc.2005.069;
RA de Albuquerque Modesto J.C., Junqueira-de-Azevedo I.L.M.,
RA Neves-Ferreira A.G.C., Fritzen M., Oliva M.L.V., Ho P.L., Perales J.,
RA Chudzinski-Tavassi A.M.;
RT "Insularinase A, a prothrombin activator from Bothrops insularis venom, is
RT a metalloprotease derived from a gene encoding protease and disintegrin
RT domains.";
RL Biol. Chem. 386:589-600(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Venom gland;
RX PubMed=12459276; DOI=10.1016/s0378-1119(02)01080-6;
RA Junqueira-de-Azevedo I.L.M., Ho P.L.;
RT "A survey of gene expression and diversity in the venom glands of the
RT pitviper snake Bothrops insularis through the generation of expressed
RT sequence tags (ESTs).";
RL Gene 299:279-291(2002).
RN [3]
RP PROTEIN SEQUENCE OF 404-423, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY,
RP AND RECOMBINANT EXPRESSION.
RC TISSUE=Venom;
RX PubMed=21073888; DOI=10.1016/j.toxicon.2010.10.013;
RA Della-Casa M.S., Junqueira-de-Azevedo I., Butera D., Clissa P.B.,
RA Lopes D.S., Serrano S.M., Pimenta D.C., Magalhaes G.S., Ho P.L.,
RA Moura-da-Silva A.M.;
RT "Insularin, a disintegrin from Bothrops insularis venom: inhibition of
RT platelet aggregation and endothelial cell adhesion by the native and
RT recombinant GST-insularin proteins.";
RL Toxicon 57:125-133(2011).
CC -!- FUNCTION: [Snake venom metalloproteinase insularinase-A]: Non-
CC hemorrhagic proteinase that activates prothrombin (F2) calcium-
CC independently. Activates factor X (F10) and hydrolyzes the Aalpha-chain
CC and more slowly the Bbeta-chain of fibrin and fibrinogen without
CC affecting the gamma chain. It induces neither detachment nor apoptosis
CC of human endothelial cells and is also not able to trigger an
CC endothelial pro-inflammatory cell response. Nitric oxide and
CC prostacyclin levels released by endothelial cells are significantly
CC increased after treatment with insularinase A.
CC {ECO:0000269|PubMed:16006246}.
CC -!- FUNCTION: [Disintegrin insularin]: Inhibits ADP-induced platelet
CC aggregation (IC(50)=0.8 uM for native protein) (PubMed:21073888).
CC Interestingly, inhibits the adhesion of HUVECs to immobilized
CC fibrinogen at very low concentrations (IC(50)=36 nM) (PubMed:21073888).
CC {ECO:0000269|PubMed:21073888}.
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 1,10-phenanthroline, but
CC not by PMSF. {ECO:0000269|PubMed:16006246}.
CC -!- SUBUNIT: Monomer (metalloprotease). {ECO:0000269|PubMed:16006246}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Not glycosylated.
CC -!- MASS SPECTROMETRY: [Snake venom metalloproteinase insularinase-A]:
CC Mass=22639; Method=MALDI; Evidence={ECO:0000269|PubMed:16006246};
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; AY736107; AAU47334.1; -; mRNA.
DR AlphaFoldDB; Q5XUW8; -.
DR SMR; Q5XUW8; -.
DR MEROPS; M12.325; -.
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:0016504; F:peptidase activator activity; IEA:UniProtKB-KW.
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; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 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 Blood coagulation cascade activating toxin; Calcium;
KW Cell adhesion impairing toxin; Direct protein sequencing; Disulfide bond;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Platelet aggregation inhibiting toxin; Protease; Prothrombin activator;
KW Pyrrolidone carboxylic acid; Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..192
FT /evidence="ECO:0000250"
FT /id="PRO_5000094063"
FT CHAIN 193..393
FT /note="Snake venom metalloproteinase insularinase-A"
FT /evidence="ECO:0000305|PubMed:16006246"
FT /id="PRO_5000094064"
FT PROPEP 394..403
FT /evidence="ECO:0000250"
FT /id="PRO_0000326262"
FT CHAIN 404..476
FT /note="Disintegrin insularin"
FT /evidence="ECO:0000305|PubMed:21073888"
FT /id="PRO_5000094065"
FT DOMAIN 198..393
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 395..476
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 454..456
FT /note="Cell attachment site"
FT /evidence="ECO:0000305|PubMed:21073888"
FT ACT_SITE 335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 334
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 338
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 193
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250"
FT DISULFID 309..388
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 348..372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 350..355
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 409..424
FT /evidence="ECO:0000250|UniProtKB:P30403"
FT DISULFID 411..419
FT /evidence="ECO:0000250|UniProtKB:P30403"
FT DISULFID 418..441
FT /evidence="ECO:0000250|UniProtKB:P30403"
FT DISULFID 432..438
FT /evidence="ECO:0000250|UniProtKB:P30403"
FT DISULFID 437..462
FT /evidence="ECO:0000250|UniProtKB:P30403"
FT DISULFID 450..469
FT /evidence="ECO:0000250|UniProtKB:P30403"
SQ SEQUENCE 476 AA; 53313 MW; 07874077D4B23515 CRC64;
MIQVLLVTIC LAAFPYQGSS IILESGNVND YEVVYARKVT ELPKGAVQQK YEDAMQYEFK
VNGEPVVLHL EKNKGLFSED YSETHYSPDG RQIITYPPFE DHCYYHGRIE NDADSTASIS
ACNGLKGHFK LQGETYLIEP LKLPDSEAHA VYKYENVEKE DEAPKMCGVT ETNWESYEPI
EKASQSNLTP EQQKFSPRYI ELAVVADHGM FTKYNSNLNT IRTRVHEMVN TLNGFFRSVN
VDASLANLEV WSKKDLIKVE KDSSKTLTSF GEWRERDLLP RISHDHAQLL TTIVFDQQTI
GLAYTAGMCD PRQSVAVVMD HSKKNLRVAV TMAHELGHNL GMDHDDTCTC GAKSCIMAST
ISKGLSFEFS KCSQNQYQTY LTDHNPQCIL NKPLTTVSGN ELLEAGEECD CGAPENPCCD
AATCKLRPRA QCAEGLCCDQ CRFKGAGKIC RRARGDNPDD RCTGQSADCP RNRFHA
