VM3V1_CROAT
ID VM3V1_CROAT Reviewed; 610 AA.
AC Q9DGB9;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like VAP1;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE AltName: Full=Vascular apoptosis-inducing protein 1;
DE Short=Vap-1;
DE Flags: Precursor;
OS Crotalus atrox (Western diamondback rattlesnake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX NCBI_TaxID=8730;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 240-251; 274-283; 378-385
RP AND 507-519, FUNCTION, AND ACTIVITY REGULATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11071872; DOI=10.1006/bbrc.2000.3770;
RA Masuda S., Ohta T., Kaji K., Fox J.W., Hayashi H., Araki S.;
RT "cDNA cloning and characterization of vascular apoptosis-inducing protein
RT 1.";
RL Biochem. Biophys. Res. Commun. 278:197-204(2000).
RN [2]
RP PROTEIN SEQUENCE OF 274-283 AND 584-591.
RC TISSUE=Venom;
RX PubMed=9578458; DOI=10.1046/j.1432-1327.1998.2530036.x;
RA Masuda S., Hayashi H., Araki S.;
RT "Two vascular apoptosis-inducing proteins from snake venom are members of
RT the metalloprotease/disintegrin family.";
RL Eur. J. Biochem. 253:36-41(1998).
RN [3]
RP PROTEIN SEQUENCE OF 51-60; 109-126 AND 258-273, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=19371136; DOI=10.1021/pr900249q;
RA Calvete J.J., Fasoli E., Sanz L., Boschetti E., Righetti P.G.;
RT "Exploring the venom proteome of the western diamondback rattlesnake,
RT Crotalus atrox, via snake venomics and combinatorial peptide ligand library
RT approaches.";
RL J. Proteome Res. 8:3055-3067(2009).
RN [4]
RP FUNCTION, SUBUNIT, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=9196035; DOI=10.1006/bbrc.1997.6728;
RA Masuda S., Araki S., Yamamoto T., Kaji K., Hayashi H.;
RT "Purification of a vascular apoptosis-inducing factor from hemorrhagic
RT snake venom.";
RL Biochem. Biophys. Res. Commun. 235:59-63(1997).
RN [5]
RP FUNCTION.
RX PubMed=11821125; DOI=10.1016/s0041-0101(01)00249-5;
RA Araki S., Masuda S., Maeda H., Ying M.J., Hayashi H.;
RT "Involvement of specific integrins in apoptosis induced by vascular
RT apoptosis-inducing protein 1.";
RL Toxicon 40:535-542(2002).
RN [6]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=15922392; DOI=10.1016/j.toxicon.2005.02.002;
RA Maruyama J., Hayashi H., Miao J., Sawada H., Araki S.;
RT "Severe cell fragmentation in the endothelial cell apoptosis induced by
RT snake apoptosis toxin VAP1 is an apoptotic characteristic controlled by
RT caspases.";
RL Toxicon 46:1-6(2005).
RN [7]
RP FUNCTION.
RX PubMed=18657564; DOI=10.1016/j.toxicon.2008.06.027;
RA Kikushima E., Nakamura S., Oshima Y., Shibuya T., Miao J.Y., Hayashi H.,
RA Nikai T., Araki S.;
RT "Hemorrhagic activity of the vascular apoptosis-inducing proteins VAP1 and
RT VAP2 from Crotalus atrox.";
RL Toxicon 52:589-593(2008).
RN [8]
RP CRYSTALLIZATION.
RC TISSUE=Venom;
RX PubMed=16820695; DOI=10.1107/s1744309106022548;
RA Igarashi T., Oishi Y., Araki S., Mori H., Takeda S.;
RT "Crystallization and preliminary X-ray crystallographic analysis of two
RT vascular apoptosis-inducing proteins (VAPs) from Crotalus atrox venom.";
RL Acta Crystallogr. F 62:688-691(2006).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 185-610, SUBUNIT, METAL-BINDING
RP SITES, GLYCOSYLATION AT ASN-218, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=16688218; DOI=10.1038/sj.emboj.7601131;
RA Takeda S., Igarashi T., Mori H., Araki S.;
RT "Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its
RT unique C-shaped scaffold.";
RL EMBO J. 25:2388-2396(2006).
CC -!- FUNCTION: Zinc metalloprotease that has fibrinogenolytic and
CC hemorrhagic activities. It induces apoptosis in vascular endothelial
CC cells (VEC), without degrading extracellular matrix (it cannot cleave
CC collagen) or inhibiting adhesion of VEC. VAP1-induced apoptosis is
CC inhibited by antibodies for integrin alpha-3, alpha-6, beta-1 and CD9.
CC Apoptosis is accompanied by severe cell fragmentation, which is
CC controlled by caspases. {ECO:0000269|PubMed:11071872,
CC ECO:0000269|PubMed:11821125, ECO:0000269|PubMed:15922392,
CC ECO:0000269|PubMed:18657564, ECO:0000269|PubMed:9196035}.
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 EGTA, but not by PMSF.
CC {ECO:0000269|PubMed:11071872}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:16688218,
CC ECO:0000269|PubMed:9196035}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:19371136}.
CC -!- TOXIC DOSE: LD(50) is 0.3 ug/ml against vascular endothelial cells in
CC culture. {ECO:0000269|PubMed:9196035}.
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; AB042840; BAB18307.1; -; mRNA.
DR PIR; JC7530; JC7530.
DR PDB; 2ERO; X-ray; 2.50 A; A/B=184-610.
DR PDB; 2ERP; X-ray; 2.95 A; A/B=184-610.
DR PDB; 2ERQ; X-ray; 2.50 A; A/B=184-610.
DR PDBsum; 2ERO; -.
DR PDBsum; 2ERP; -.
DR PDBsum; 2ERQ; -.
DR AlphaFoldDB; Q9DGB9; -.
DR SMR; Q9DGB9; -.
DR MEROPS; M12.186; -.
DR iPTMnet; Q9DGB9; -.
DR EvolutionaryTrace; Q9DGB9; -.
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 3D-structure; Apoptosis; Calcium; Cell adhesion impairing toxin;
KW Direct protein sequencing; Disulfide bond; Fibrinogenolytic toxin;
KW Glycoprotein; Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Pyrrolidone carboxylic acid;
KW Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..189
FT /evidence="ECO:0000250"
FT /id="PRO_0000340299"
FT CHAIN 190..610
FT /note="Zinc metalloproteinase-disintegrin-like VAP1"
FT /id="PRO_0000340300"
FT DOMAIN 199..395
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 403..488
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 467..469
FT /note="D/ECD-tripeptide"
FT ACT_SITE 336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 335
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 405
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 410
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 412
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 418
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 472
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 484
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT MOD_RES 190
FT /note="Pyrrolidone carboxylic acid (Glu)"
FT /evidence="ECO:0000250|UniProtKB:P0DM89"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 310..390
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 350..374
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 352..357
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 365
FT /note="Interchain (with C-365)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000269|PubMed:16688218"
FT DISULFID 406..435
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 417..430
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 419..425
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 429..452
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 443..449
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 448..474
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 461..481
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 468..499
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 492..504
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 511..561
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 526..572
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 539..549
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 556..598
FT /evidence="ECO:0000269|PubMed:16688218"
FT DISULFID 592..603
FT /evidence="ECO:0000269|PubMed:16688218"
FT HELIX 189..196
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 199..207
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 219..238
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 264..278
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 279..282
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 286..292
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 316..320
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 326..340
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 373..386
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 432..434
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 465..469
FT /evidence="ECO:0007829|PDB:2ERP"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 507..515
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 524..531
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 539..547
FT /evidence="ECO:0007829|PDB:2ERO"
FT HELIX 551..556
FT /evidence="ECO:0007829|PDB:2ERO"
FT TURN 581..584
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:2ERO"
FT STRAND 596..605
FT /evidence="ECO:0007829|PDB:2ERO"
SQ SEQUENCE 610 AA; 67960 MW; 9E5F4EFE092E2141 CRC64;
MIQVLLVTIS LAVFPYQGSS VILESGNVND YEVVYPRKVT ALPKGAVQPK YEDAMQYEFK
VNGEPVVLHL EKNKGLFSED YSETHYSPDG REITTYPPVE DHCYYHGRIE NDADSTASIS
ACNGLKGHFK LQGEMYLIEP LKLPDSEAHA VFKYENVEKE DEAPKMCGVT QNWESYEPIK
KASQSNLTPE QQRYLNAKKY VKLFLVADYI MYLKYGRNLT AVRTRMYDIV NVITPIYHRM
NIHVALVGLE IWSNTDKIIV QSSADVTLDL FAKWRATDLL SRKSHDNAQL LTGINFNGPT
AGLGYLGGIC NTMYSAGIVQ DHSKIHHLVA IAMAHEMGHN LGMDHDKDTC TCGTRPCVMA
GALSCEASFL FSDCSQKDHR EFLIKNMPQC ILKKPLKTDV VSPAVCGNYF VEVGEECDCG
SPRTCRDPCC DATTCKLRQG AQCAEGLCCD QCRFKGAGTE CRAAKDECDM ADVCTGRSAE
CTDRFQRNGQ PCKNNNGYCY NGKCPIMADQ CIALFGPGAT VSQDACFQFN REGNHYGYCR
KEQNTKIACE PQDVKCGRLY CFPNSPENKN PCNIYYSPND EDKGMVLPGT KCADRKACSN
GQCVDVTTPY
