VM3VB_MACLB
ID VM3VB_MACLB Reviewed; 614 AA.
AC Q4VM07;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like VLAIP-B;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
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 229-241; 317-327; 338-348;
RP 359-379; 440-456; 460-491; 501-513; 563-573 AND 588-614, PYROGLUTAMATE
RP FORMATION AT GLN-194, 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: This metalloproteinase hydrolyzes azocasein, and insulin B-
CC chain (at the '38-Ala-|-Leu-39' bond). Also hydrolyzes the Aalpha-chain
CC (FGA) and more slowly the Bbeta-chain of fibrinogen (FGB), without
CC affecting the gamma-chain. Cleaves alpha-chain of fibrinogen at '432-
CC Lys-|-Leu-433' and '535-Pro-|-Met-536' bonds. Does not cleave fibrin.
CC Inhibits endothelial cell adhesion to extracellular matrix proteins
CC such as fibrinogen, fibronectin, vitronectin, collagen I, and collagen
CC IV. Induces apoptosis in vascular endothelial cells.
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 -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIc sub-subfamily. {ECO:0000305}.
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DR EMBL; AY835997; AAX38182.1; -; mRNA.
DR AlphaFoldDB; Q4VM07; -.
DR SMR; Q4VM07; -.
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..193
FT /evidence="ECO:0000250"
FT /id="PRO_0000340314"
FT CHAIN 194..614
FT /note="Zinc metalloproteinase-disintegrin-like VLAIP-B"
FT /id="PRO_0000340315"
FT DOMAIN 202..398
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 406..492
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 470..472
FT /note="D/ECD-tripeptide"
FT ACT_SITE 339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 205
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 289
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 338
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 342
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 348
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 413
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 418
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 421
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 194
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000305|PubMed:15922394"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 313..393
FT /evidence="ECO:0000250"
FT DISULFID 353..377
FT /evidence="ECO:0000250"
FT DISULFID 355..360
FT /evidence="ECO:0000250"
FT DISULFID 368
FT /note="Interchain (with C-369 in VLAIP-A)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 409..438
FT /evidence="ECO:0000250"
FT DISULFID 420..433
FT /evidence="ECO:0000250"
FT DISULFID 422..428
FT /evidence="ECO:0000250"
FT DISULFID 432..455
FT /evidence="ECO:0000250"
FT DISULFID 446..452
FT /evidence="ECO:0000250"
FT DISULFID 451..477
FT /evidence="ECO:0000250"
FT DISULFID 464..484
FT /evidence="ECO:0000250"
FT DISULFID 471..503
FT /evidence="ECO:0000250"
FT DISULFID 496..508
FT /evidence="ECO:0000250"
FT DISULFID 515..565
FT /evidence="ECO:0000250"
FT DISULFID 530..576
FT /evidence="ECO:0000250"
FT DISULFID 543..553
FT /evidence="ECO:0000250"
FT DISULFID 560..602
FT /evidence="ECO:0000250"
FT DISULFID 596..607
FT /evidence="ECO:0000250"
SQ SEQUENCE 614 AA; 68843 MW; CE4F4912493CDAC9 CRC64;
MMQVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPQKIT ALPKGAIQQP EQKYEDAIKY
EFKVNGKPVV LHLEKNKGLF SEDYSETHYT PDGREITINP PVEDHCYYHG RIQNDADSTA
SISACNGLKG HFKLQGEMYL IEPLRIPDSE AHAIYKYENI EKEDEAPKMC GVTQTNWESD
EPIKASQLNL TPEQRTYLKS KKYVELVIVA DYIMFWKYDR SLSTIRTRIY EIVNTLNVIY
RFLNIYIALV AVEIWSKGDL INVTSSAYDT LDSFGEWRER DLLNRKRHDN AQLLTGINFN
GPSAGRGFVG RMCQPKYSVG IVQDHSKIYL LVASAMAHEM GHNLGMDHDR IDCTCGAKSC
IMSGILRCET SYLFSDCSRE EHRKYLINKM PQCILNKPLK TDIVSPAVCG NYFVEVGEEC
DCGSPANCQD RCCDAATCKL RPGAQCGDGV CCYQCKFRRA GTVCRPANGE CDVSDLCTGQ
SAECPTDQFQ RNGQPCQNNK GYCYNGTCPI MEKQCISLFG ASATVAQDSC FQFNRRGNHY
GYCRKENNTK IACAPEDVKC GRLYCLDNSS GHKNPCQIYY IPSDENKGMV DPGTKCGDGM
VCSNGKCVDV TIAY
