VM3VA_MACLB
ID VM3VA_MACLB Reviewed; 616 AA.
AC Q4VM08;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like VLAIP-A;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE AltName: Full=Vipera lebetina apoptosis-inducing protein;
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 198-203; 270-277; 362-374;
RP 391-401; 441-457; 461-492; 552-560; 575-596 AND 608-616, PYROGLUTAMATE
RP FORMATION AT GLN-195, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND SUBUNIT.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15922394; DOI=10.1016/j.toxicon.2005.03.008;
RA Trummal K., Tonismagi K., Siigur E., Aaspollu A., Lopp A., Sillat T.,
RA Saat R., Kasak L., Tammiste I., Kogerman P., Kalkkinen N., Siigur J.;
RT "A novel metalloprotease from Vipera lebetina venom induces human
RT endothelial cell apoptosis.";
RL Toxicon 46:46-61(2005).
CC -!- FUNCTION: Snake venom zinc metalloprotease that hydrolyzes the alpha-
CC chain (FGA) and more slowly the beta-chain (FGB) of fibrinogen, without
CC affecting the gamma-chain. Cleaves alpha-chain of fibrinogen at '432-
CC Lys-|-Leu-433' and '535-Pro-|-Met-536' bonds. Induces apoptosis in
CC vascular endothelial cells and inhibits endothelial cell adhesion to
CC extracellular matrix proteins such as fibrinogen, fibronectin,
CC vitronectin, collagen I, and collagen IV. Also hydrolyzes azocasein,
CC and insulin B-chain (at the '38-Ala-|-Leu-39' bond).
CC {ECO:0000269|PubMed:15922394}.
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 or 1,10-phenanthroline. Not
CC inhibited by PMSF. {ECO:0000269|PubMed:15922394}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked. {ECO:0000269|PubMed:15922394}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:15922394}.
CC -!- MISCELLANEOUS: Does not cleave fibrin. {ECO:0000305|PubMed:15922394}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIc sub-subfamily. {ECO:0000305}.
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DR EMBL; AY835996; AAX38181.1; -; mRNA.
DR AlphaFoldDB; Q4VM08; -.
DR SMR; Q4VM08; -.
DR MEROPS; M12.315; -.
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:0006915; P:apoptotic process; 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; 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 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; 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 Apoptosis; Calcium; Cell adhesion impairing toxin;
KW Direct protein sequencing; Disulfide bond; Fibrinogenolytic toxin;
KW Glycoprotein; Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Pyrrolidone carboxylic acid; Secreted; Signal;
KW Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..194
FT /evidence="ECO:0000250"
FT /id="PRO_0000340312"
FT CHAIN 195..616
FT /note="Zinc metalloproteinase-disintegrin-like VLAIP-A"
FT /id="PRO_0000340313"
FT DOMAIN 203..399
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 407..493
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 471..473
FT /note="D/ECD-tripeptide"
FT ACT_SITE 340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 349
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 414
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 416
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 419
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 422
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:0000305|PubMed:15922394"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 314..394
FT /evidence="ECO:0000250"
FT DISULFID 354..378
FT /evidence="ECO:0000250"
FT DISULFID 356..361
FT /evidence="ECO:0000250"
FT DISULFID 369
FT /note="Interchain (with C-368 in VLAIP-B)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 410..439
FT /evidence="ECO:0000250"
FT DISULFID 421..434
FT /evidence="ECO:0000250"
FT DISULFID 423..429
FT /evidence="ECO:0000250"
FT DISULFID 433..456
FT /evidence="ECO:0000250"
FT DISULFID 447..453
FT /evidence="ECO:0000250"
FT DISULFID 452..478
FT /evidence="ECO:0000250"
FT DISULFID 465..485
FT /evidence="ECO:0000250"
FT DISULFID 472..504
FT /evidence="ECO:0000250"
FT DISULFID 497..509
FT /evidence="ECO:0000250"
FT DISULFID 516..566
FT /evidence="ECO:0000250"
FT DISULFID 531..577
FT /evidence="ECO:0000250"
FT DISULFID 544..554
FT /evidence="ECO:0000250"
FT DISULFID 561..603
FT /evidence="ECO:0000250"
FT DISULFID 597..609
FT /evidence="ECO:0000250"
SQ SEQUENCE 616 AA; 68710 MW; 08535A52136D43AA CRC64;
MMQVLLVTIS LAVFPYQGSS IILESGNVND YEVVYPQKVT AMPKGAVKQP EQKYEDAMQY
EFKVKGEPVV LLLEKNKDLF SEDYSETHYS PDGREITTNP PVEDHCYYHG RIQNDADSSA
SISACNGLKG HFMLQGETYL IEPLKLPDSE AHAVYKYENV EKEDEAPKMC GVTQTNWESD
EPIKKASQLN LTPEQRRYLN SPKYIKLVIV ADYIMFLKYG RSLITIRTRI YEIVNILNVI
YRVLNIYIAL LGLEIWNNGD KINVLPETKV TLDLFGKWRE RDLLNRRKHD NAQLLTDINF
NGPTAGLGYV GSMCDPQYSA GIVQDHNKVN FLVALAMAHE MGHNLGMEHD EIHCTCGAKS
CIMSGTLSCE ASIRFSNCSR EEHQKYLINK MPQCILNKPL KTDIVSPAVC GNYLVELGED
CDCGSPRDCQ NPCCNAATCK LTPGSQCADG ECCDQCKFRR AGTVCRPANG ECDVSDLCTG
QSAECPTDQF QRNGQPCQNN NGYCYSGTCP IMGKQCISLF GASATVAQDA CFQFNSLGNE
YGYCRKENGR KIPCAPQDVK CGRLYCFDNL PEHKNPCQIY YTPSDENKGM VDPGTKCGDG
KACSSNRQCV DVNTAY
