VM2L2_MACLB
ID VM2L2_MACLB Reviewed; 478 AA.
AC Q98995;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase lebetase;
DE Short=SVMP;
DE EC=3.4.24.-;
DE AltName: Full=Fibrinolytic protease;
DE AltName: Full=Le-3;
DE Short=Le3;
DE AltName: Full=Lebetase II;
DE AltName: Full=Lebetase-2;
DE Contains:
DE RecName: Full=Disintegrin VLE5A;
DE Flags: Precursor;
OS Macrovipera lebetina (Levantine viper) (Vipera lebetina).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Macrovipera.
OX NCBI_TaxID=8709;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-236, FUNCTION OF THE
RP METALLOPROTEINASE, SUBUNIT, AND PYROGLUTAMATE FORMATION AT GLN-195.
RC TISSUE=Venom, and Venom gland;
RX PubMed=8694817; DOI=10.1006/bbrc.1996.1012;
RA Siigur E., Aaspollu A., Tu A.T., Siigur J.;
RT "cDNA cloning and deduced amino acid sequence of fibrinolytic enzyme
RT (lebetase) from Vipera lebetina snake venom.";
RL Biochem. Biophys. Res. Commun. 224:229-236(1996).
RN [2]
RP FUNCTION OF THE METALLOPROTEINASE, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=2065076; DOI=10.1016/0304-4165(91)90156-b;
RA Siigur E., Siigur J.;
RT "Purification and characterization of lebetase, a fibrinolytic enzyme from
RT Vipera lebetina (snake) venom.";
RL Biochim. Biophys. Acta 1074:223-229(1991).
RN [3]
RP FUNCTION OF THE METALLOPROTEINASE, ACTIVITY REGULATION, SUBUNIT OF THE
RP METALLOPROTEINASE, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=9678676; DOI=10.1016/s0049-3848(98)00009-7;
RA Siigur J., Samel M., Tonismagi K., Subbi J., Siigur E., Tu A.T.;
RT "Biochemical characterization of lebetase, a direct-acting fibrinolytic
RT enzyme from Vipera lebetina snake venom.";
RL Thromb. Res. 90:39-49(1998).
RN [4]
RP FUNCTION OF THE METALLOPROTEINASE.
RX PubMed=10556563; DOI=10.1016/s0167-4838(99)00164-8;
RA Saidi N., Samel M., Siigur J., Jensen P.E.H.;
RT "Lebetase, an alpha(beta)-fibrin(ogen)olytic metalloproteinase of Vipera
RT lebetina snake venom, is inhibited by human alpha-macroglobulins.";
RL Biochim. Biophys. Acta 1434:94-102(1999).
RN [5]
RP FUNCTION OF THE METALLOPROTEINASE.
RX PubMed=10669797; DOI=10.1016/s0167-4838(99)00236-8;
RA Trummal K., Vija H., Subbi J., Siigur J.;
RT "MALDI-TOF mass spectrometry analysis of substrate specificity of lebetase,
RT a direct-acting fibrinolytic metalloproteinase from Vipera lebetina snake
RT venom.";
RL Biochim. Biophys. Acta 1476:331-336(2000).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11910177; DOI=10.1159/000048055;
RA Siigur J., Aaspollu A., Tonismagi K., Trummal K., Samel M., Vija H.,
RA Subbi J., Siigur E.;
RT "Proteases from Vipera lebetina venom affecting coagulation and
RT fibrinolysis.";
RL Haemostasis 31:123-132(2001).
CC -!- FUNCTION: [Snake venom metalloproteinase lebetase]: Fibrinolytic and
CC fibrinogenolytic metalloproteinase that hydrolyzes the Aalpha-chain and
CC more slowly the Bbeta-chain of fibrin and fibrinogen. Its fibrinolytic
CC activity is direct, without any plasminogen activation. Also hydrolyzes
CC casein and B-chain of oxidized insulin. Inhibits ADP-induced and
CC collagen-induced platelet aggregation. Shows low hemorrhagic activity.
CC Cleaves the plasma proteinase inhibitors alpha(2)-macroglobulin (A2M)
CC and pregnancy zone protein (PZP), and is inhibited by them. The
CC metalloprotease has no strict P1-P1' specificity requirement.
CC Hydrolysis at sites with a Pro residue at P1 is observed with
CC bradykinin, substance P, PZP and alpha chain fibrinogen (FGA)
CC (PubMed:11910177). {ECO:0000269|PubMed:10556563,
CC ECO:0000269|PubMed:10669797, ECO:0000269|PubMed:11910177,
CC ECO:0000269|PubMed:2065076, ECO:0000269|PubMed:8694817,
CC ECO:0000269|PubMed:9678676}.
CC -!- FUNCTION: [Disintegrin VLE5A]: Poor inhibitor of platelet aggregation.
CC The disintegrin inhibits the adhesion of the alpha-4/beta-1
CC (ITGA4/ITGB1) integrin to VCAM-1. Inhibition on alpha-2b/beta-3
CC (ITGA2B/ITGB3) is low (By similarity). {ECO:0000250}.
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: Fibrinolytic and caseinolytic activities are
CC inhibited by Cd(2+), Cu(2+) and Co(2+) ions. Not inhibited by Mg(2+),
CC Ca(2+) and Ba(2+). Also inhibited by EDTA, EGTA and 1,10-
CC phenanthroline. {ECO:0000269|PubMed:2065076,
CC ECO:0000269|PubMed:9678676}.
CC -!- SUBUNIT: Monomer (metalloproteinase). Heterodimer; disulfide-linked
CC (disintegrin) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: [Snake venom metalloproteinase lebetase]:
CC Mass=22912; Mass_error=20; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9678676};
CC -!- MISCELLANEOUS: 2 lebetase isoforms have been isolated designated
CC lebetase I (22.719 Da, pI 5.0) and lebetase II (22.912 Da, pI 5.3).
CC {ECO:0000305|PubMed:10556563}.
CC -!- MISCELLANEOUS: Disintegrin VLE5A does not interact with the collagen-
CC binding alpha-1/beta-1 (ITGA1/ITGB1) and alpha-2/beta-1 (ITGA2/ITGB1)
CC integrins. {ECO:0000250}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the dimeric disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIe sub-subfamily. {ECO:0000305}.
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DR EMBL; X97894; CAA66471.1; -; mRNA.
DR PIR; JC4880; JC4880.
DR AlphaFoldDB; Q98995; -.
DR SMR; Q98995; -.
DR MEROPS; M12.164; -.
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; 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 Calcium; Cell adhesion impairing toxin; Direct protein sequencing;
KW Disulfide bond; Fibrinogenolytic toxin; Fibrinolytic 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..194
FT /id="PRO_0000318582"
FT CHAIN 195..397
FT /note="Snake venom metalloproteinase lebetase"
FT /id="PRO_5000146862"
FT PROPEP 398..413
FT /evidence="ECO:0000250"
FT /id="PRO_0000318583"
FT CHAIN 414..478
FT /note="Disintegrin VLE5A"
FT /id="PRO_5000146863"
FT DOMAIN 201..397
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 405..478
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 456..458
FT /note="Cell attachment site; atypical (VGD)"
FT ACT_SITE 338
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 347
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 195
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250"
FT DISULFID 312..392
FT /evidence="ECO:0000250"
FT DISULFID 352..376
FT /evidence="ECO:0000250"
FT DISULFID 354..359
FT /evidence="ECO:0000250"
FT DISULFID 426..440
FT /evidence="ECO:0000250"
FT DISULFID 434..464
FT /evidence="ECO:0000250"
FT DISULFID 439..443
FT /evidence="ECO:0000250"
FT DISULFID 452..471
FT /evidence="ECO:0000250"
SQ SEQUENCE 478 AA; 53480 MW; 781915F7D897BF03 CRC64;
MIQVLLVTIC LAVFPYQGSS KTLKSGNVND YEVVNPQAVT GLPKGAVKQP EKKYEDTMQY
EFEVNGEPVV LHLEKNRGLF SKDYSETHYS PDGREITTNP AVEDHCYYHG RIQNDADSTA
SISACNGLKG YFTLRGETYL IEPLKLPDSE AHAVYKYENI EKEDEAPKMC GVTQTNWASD
EPIKKASQLN LTPEQQRFEP RYIELVIVAD HAMVTKYNGD LAAITTWVHQ LVNNINGFYR
DLNVHITLSA VEVWTNGDLI NVQPAASVTL NLFGEWRERD LLNRRMHDHA QLLTGIDLDD
NIIGLAYDDS MCDPRYSVGI VQDHSAIIRL VAVTMAHELG HNLGMNHDGD QCNCGANGCV
MSVVLIEQRS YQFSDCSKNK YQTYLTNRNP QCILNQPLRT DTVSTPVSGN ELLQNSGNPC
CDPVTCQPRR GEHCVSGKCC RNCKFLRAGT VCKRAVGDDM DDYCTGISSD CPRNPYKD
