ID VM3BP_BOTJA Reviewed; 610 AA.
AC O93523;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 2.
DT 22-FEB-2023, entry version 118.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like bothropasin {ECO:0000303|PubMed:6819660};
DE EC=3.4.24.49;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Contains:
DE RecName: Full=Disintegrin-like bothropasin;
DE Flags: Precursor;
OS Bothrops jararaca (Jararaca) (Bothrops jajaraca).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8724;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 248-253; 257-268; 273-276;
RP 296-303 AND 395-420, AND FUNCTION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=12565741; DOI=10.1016/s0041-0101(02)00279-9;
RA Assakura M.T., Silva C.A., Mentele R., Camargo A.C.M., Serrano S.M.T.;
RT "Molecular cloning and expression of structural domains of bothropasin, a
RT P-III metalloproteinase from the venom of Bothrops jararaca.";
RL Toxicon 41:217-227(2003).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=6819660; DOI=10.1016/0041-0101(82)90098-8;
RA Mandelbaum F.R., Reichel A.P., Assakura M.T.;
RT "Isolation and characterization of a proteolytic enzyme from the venom of
RT the snake Bothrops jararaca (Jararaca).";
RL Toxicon 20:955-972(1982).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 192-610 IN COMPLEX WITH ZINC AND
RP CALCIUM IONS, COFACTOR, METAL-BINDING SITES, GLYCOSYLATION AT ASN-372,
RP PYROGLUTAMATE FORMATION AT GLN-192, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=18831982; DOI=10.1016/j.toxicon.2008.08.021;
RA Muniz J.R.C., Ambrosio A.L.B., Selistre-de-Araujo H.S., Cominetti M.R.,
RA Moura-da-Silva A.M., Oliva G., Garratt R.C., Souza D.H.F.;
RT "The three-dimensional structure of bothropasin, the main hemorrhagic
RT factor from Bothrops jararaca venom: insights for a new classification of
RT snake venom metalloprotease subgroups.";
RL Toxicon 52:807-816(2008).
CC -!- FUNCTION: [Zinc metalloproteinase-disintegrin-like bothropasin]: Has
CC caseinolytic activity. Causes hemorrhage on rabbit skin and causes
CC myonecrosis in mouse tibialis anterior muscle.
CC -!- FUNCTION: [Disintegrin-like bothropasin]: Inhibits platelet
CC aggregation.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of 5-His-|-Leu-6, 10-His-|-Leu-11, 14-Ala-|-Leu-15,
CC 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 in insulin B chain.;
CC EC=3.4.24.49; Evidence={ECO:0000269|PubMed:6819660};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18831982};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18831982};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and EGTA.
CC {ECO:0000269|PubMed:6819660}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:18831982,
CC ECO:0000269|PubMed:6819660}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MISCELLANEOUS: The metalloproteinase domain which is released from the
CC cleavage of the disintegrin bothropasin may be unstable.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIb sub-subfamily. {ECO:0000305}.
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DR EMBL; AF056025; AAC61986.2; -; mRNA.
DR PDB; 3DSL; X-ray; 2.70 A; A/B=192-610.
DR PDBsum; 3DSL; -.
DR AlphaFoldDB; O93523; -.
DR SMR; O93523; -.
DR MEROPS; M12.140; -.
DR iPTMnet; O93523; -.
DR KEGG; ag:AAC61986; -.
DR BRENDA; 3.4.24.49; 911.
DR EvolutionaryTrace; O93523; -.
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; Collagenase (Catalytic Domain); 1.
DR Gene3D; 4.10.70.10; Disintegrin domain; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
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 PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1.
DR PANTHER; PTHR11905:SF32; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 28; 1.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; Blood coagulation inhibitor (disintegrin); 1.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 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; Glycoprotein; Hemorrhagic toxin;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Platelet aggregation inhibiting toxin; Protease;
KW Pyrrolidone carboxylic acid; Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..191
FT /evidence="ECO:0000250"
FT /id="PRO_0000326418"
FT CHAIN 192..610
FT /note="Zinc metalloproteinase-disintegrin-like bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982"
FT /id="PRO_0000326419"
FT CHAIN 399..610
FT /note="Disintegrin-like bothropasin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000326420"
FT DOMAIN 198..394
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 402..488
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 466..468
FT /note="D/ECD-tripeptide"
FT ACT_SITE 335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 334
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 338
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 404
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 407
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 414
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 417
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT BINDING 484
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT SITE 378
FT /note="Necessary, but not sufficient, for proteolytic
FT processing"
FT /evidence="ECO:0000250"
FT MOD_RES 192
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:18831982"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18831982"
FT DISULFID 309..389
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 349..373
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 351..356
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 405..434
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 405..424
FT /note="In disintegrin-like bothropasin; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 416..434
FT /note="In disintegrin-like bothropasin; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 416..429
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 418..424
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 428..451
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 442..448
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 447..473
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 460..480
FT /note="In both disintegrin-like bothropasin and zinc
FT metalloproteinase-disintegrin-like bothropasin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000269|PubMed:18831982, ECO:0000312|PDB:3DSL"
FT DISULFID 467..499
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 467..492
FT /note="In disintegrin-like bothropasin; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 492..504
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 499..504
FT /note="In disintegrin-like bothropasin"
FT /evidence="ECO:0000250"
FT DISULFID 511..561
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 511..526
FT /note="In disintegrin-like bothropasin; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 526..572
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 539..549
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 549..556
FT /note="In disintegrin-like bothropasin; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 556..598
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 561..572
FT /note="In disintegrin-like bothropasin"
FT /evidence="ECO:0000250"
FT DISULFID 592..603
FT /note="In zinc metalloproteinase-disintegrin-like
FT bothropasin; alternate"
FT /evidence="ECO:0000269|PubMed:18831982,
FT ECO:0000312|PDB:3DSL"
FT DISULFID 598..603
FT /note="In disintegrin-like bothropasin"
FT /evidence="ECO:0000250"
SQ SEQUENCE 610 AA; 68213 MW; 014C8AE6B86F25DD CRC64;
MIEVLLVTIC LAAFPYQGSS IILESGNVND YEVVYPRKVT ALPKGAVQPK YEDAMQYEFK
VNGEPVVLHL EKNKGLFSKD YSETHYSPDG REITTYPAVE DHCYYHGRIE NDADSTASIS
ACNGLKGHFK LQRETYFIEP LKLSNSEAHA VFKYENVEKE DEAPKMCGVT QNWKSYEPIK
KASQLVVTAE QQKYNPFRYV ELFIVVDQGM VTKNNGDLDK IKARMYELAN IVNEILRYLY
MHAALVGLEI WSNGDKITVK PDVDYTLNSF AEWRKTDLLT RKKHDNAQLL TAIDFNGPTI
GYAYIGSMCH PKRSVAIVED YSPINLVVAV IMAHEMGHNL GIHHDTDFCS CGDYPCIMGP
TISNEPSKFF SNCSYIQCWD FIMKENPQCI LNEPLGTDIV SPPVCGNELL EVGEECDCGT
PENCQNECCD AATCKLKSGS QCGHGDCCEQ CKFSKSGTEC RASMSECDPA EHCTGQSSEC
PADVFHKNGQ PCLDNYGYCY NGNCPIMYHQ CYALFGADVY EAEDSCFKDN QKGNYYGYCR
KENGKKIPCA PEDVKCGRLY CKDNSPGQNN PCKMFYSNDD EHKGMVLPGT KCADGKVCSN
GHCVDVATAY
//
