VM3VA_CROAT
ID VM3VA_CROAT Reviewed; 607 AA.
AC A4PBQ9;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like VAP2A;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE AltName: Full=Vascular apoptosis-inducing protein 2A;
DE Short=VAP2A;
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 211-217; 226-236; 240-250
RP AND 505-517, AND SUBUNIT.
RC TISSUE=Venom, and Venom gland;
RX PubMed=17497365; DOI=10.1080/10623320701346882;
RA Masuda S., Maeda H., Miao J.Y., Hayashi H., Araki S.;
RT "cDNA cloning and some additional peptide characterization of a single-
RT chain vascular apoptosis-inducing protein, VAP2.";
RL Endothelium 14:89-96(2007).
RN [2]
RP PROTEIN SEQUENCE OF 226-236 AND 240-250, FUNCTION, AND TOXIC DOSE.
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 IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=24297900; DOI=10.1073/pnas.1314702110;
RA Vonk F.J., Casewell N.R., Henkel C.V., Heimberg A.M., Jansen H.J.,
RA McCleary R.J., Kerkkamp H.M., Vos R.A., Guerreiro I., Calvete J.J.,
RA Wuster W., Woods A.E., Logan J.M., Harrison R.A., Castoe T.A.,
RA de Koning A.P., Pollock D.D., Yandell M., Calderon D., Renjifo C.,
RA Currier R.B., Salgado D., Pla D., Sanz L., Hyder A.S., Ribeiro J.M.,
RA Arntzen J.W., van den Thillart G.E., Boetzer M., Pirovano W., Dirks R.P.,
RA Spaink H.P., Duboule D., McGlinn E., Kini R.M., Richardson M.K.;
RT "The king cobra genome reveals dynamic gene evolution and adaptation in the
RT snake venom system.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20651-20656(2013).
CC -!- FUNCTION: Heterodimeric zinc metalloprotease VAP2 that induces
CC apoptosis in endothelial cells, without triggering cell detachment.
CC {ECO:0000269|PubMed:9578458}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Heterodimer of VAP2A and VAP2B; non-covalently linked.
CC {ECO:0000269|PubMed:17497365}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 0.1 ug/ml against vascular endothelial cells in
CC culture. {ECO:0000269|PubMed:9578458}.
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; AB257084; BAF56420.1; -; mRNA.
DR AlphaFoldDB; A4PBQ9; -.
DR SMR; A4PBQ9; -.
DR MEROPS; M12.332; -.
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; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Secreted; Signal; Toxin; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..189
FT /evidence="ECO:0000250"
FT /id="PRO_0000406907"
FT CHAIN 190..607
FT /note="Zinc metalloproteinase-disintegrin-like VAP2A"
FT /id="PRO_0000406908"
FT DOMAIN 198..393
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 401..487
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 459..472
FT /note="Inhibits platelet aggregation"
FT /evidence="ECO:0000250"
FT MOTIF 465..467
FT /note="D/ECD-tripeptide"
FT ACT_SITE 334
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:0000250"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
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 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 403
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 410
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 416
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 482
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 308..388
FT /evidence="ECO:0000250"
FT DISULFID 348..372
FT /evidence="ECO:0000250"
FT DISULFID 350..355
FT /evidence="ECO:0000250"
FT DISULFID 404..433
FT /evidence="ECO:0000250"
FT DISULFID 415..428
FT /evidence="ECO:0000250"
FT DISULFID 417..423
FT /evidence="ECO:0000250"
FT DISULFID 427..450
FT /evidence="ECO:0000250"
FT DISULFID 441..447
FT /evidence="ECO:0000250"
FT DISULFID 446..472
FT /evidence="ECO:0000250"
FT DISULFID 459..479
FT /evidence="ECO:0000250"
FT DISULFID 491..501
FT /evidence="ECO:0000250"
FT DISULFID 508..558
FT /evidence="ECO:0000250"
FT DISULFID 523..569
FT /evidence="ECO:0000250"
FT DISULFID 536..546
FT /evidence="ECO:0000250"
FT DISULFID 553..595
FT /evidence="ECO:0000250"
FT DISULFID 589..600
FT /evidence="ECO:0000250"
SQ SEQUENCE 607 AA; 68035 MW; 7CA5D7EFAC9E04FD CRC64;
MIQVLLVTIC LAAFPYQGSS IILESGNVND YEIVYPRKVT ALPKGAVQPK YEDAMQYELK
VNGEPVVLHL EKNKQLFSKD YSETHYSPDG REITTYPLVE DHCYYHGRIE NDADSTASIS
ACNGLKGHFK LQGEMYLIEP LKLSDSEAHA VYKYENVEKE DEAPKMCGVT QNWKSYEPIK
KASQLVVTAE HQKYNPFRFV ELVLVVDKAM VTKNNGDLDK IKTRMYELAN TVNDIYRYMY
IHVALVGLEI WSNEDKITVK PEADYTLNAF GEWRKTDLLT RKKHDNAQLL TAIDLDRVIG
LAYVGSMCHP KRSTGIIQDY SPINLVVAVI MAHEMGHNLG INHDRGYCSC GDYACIMRPE
ISPEPSTFFS NCSYFDCWDF ITNHNPECIV NEPLGTDIIS PPVCGNELLE VGEECDCGTP
ENCQNECCDA ATCKLKSGSQ CGHGDCCEQC KFSKSGTECR ASMSECDPAE HCTGQSSECP
ADVFHKNGQP CLDNYGYNGN CPIMYHQCYD LFGADVYEAE DSCFERNQKG NYYGYCRKEN
GNKIPCAPED VKCGRLYCKD NSPGQNNSCK MFYSNEDEHK GMVLPGTKCA DGKVCSNGHC
VDVATAY
