VM3AA_CROAT
ID VM3AA_CROAT Reviewed; 419 AA.
AC Q92043;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like atrolysin-A;
DE EC=3.4.24.1 {ECO:0000269|PubMed:2817904};
DE AltName: Full=Alpha-proteinase;
DE AltName: Full=Hemorrhagic toxin A;
DE Short=HT-A;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Flags: Fragment;
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].
RC TISSUE=Venom gland;
RX PubMed=8311451; DOI=10.1006/abbi.1994.1026;
RA Hite L.A., Jia L.-G., Bjarnason J.B., Fox J.W.;
RT "cDNA sequences for four snake venom metalloproteinases: structure,
RT classification, and their relationship to mammalian reproductive
RT proteins.";
RL Arch. Biochem. Biophys. 308:182-191(1994).
RN [2]
RP PROTEIN SEQUENCE OF 7-17 AND 261-272, 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 [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2817904; DOI=10.1016/0003-9861(89)90350-0;
RA Baramova E.N., Shannon J.D., Bjarnason J.B., Fox J.W.;
RT "Degradation of extracellular matrix proteins by hemorrhagic
RT metalloproteinases.";
RL Arch. Biochem. Biophys. 275:63-71(1989).
RN [4]
RP FUNCTION.
RX PubMed=10620350; DOI=10.1006/abbi.1999.1517;
RA Jia L.G., Wang X.M., Shannon J.D., Bjarnason J.B., Fox J.W.;
RT "Inhibition of platelet aggregation by the recombinant cysteine-rich domain
RT of the hemorrhagic snake venom metalloproteinase, atrolysin A.";
RL Arch. Biochem. Biophys. 373:281-286(2000).
RN [5]
RP FUNCTION.
RX PubMed=12914938; DOI=10.1016/s0014-5793(03)00799-3;
RA Kamiguti A.S., Gallagher P., Marcinkiewicz C., Theakston R.D., Zuzel M.,
RA Fox J.W.;
RT "Identification of sites in the cysteine-rich domain of the class P-III
RT snake venom metalloproteinases responsible for inhibition of platelet
RT function.";
RL FEBS Lett. 549:129-134(2003).
CC -!- FUNCTION: Snake venom zinc metalloproteinase-disintegrin that causes
CC hemorrhage by provoking the degradation of the sub-endothelial matrix
CC proteins (fibronectin, laminin, type IV collagen, nidogen, and
CC gelatins) and disturbances in platelet function. The recombinant
CC cysteine-rich domain interacts with the alpha-2/beta-1 integrin
CC (ITGA2/ITGB1) (collagen receptor), and inhibits the platelet
CC aggregation induced by collagen. {ECO:0000269|PubMed:10620350,
CC ECO:0000269|PubMed:12914938, ECO:0000269|PubMed:2817904}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of 3-Asn-|-Gln-4, 5-His-|-Leu-6, 10-His-|-Leu-11, 14-
CC Ala-|-Leu-15 and 16-Tyr-|-Leu-17 in insulin B chain. Removes C-
CC terminal Leu from small peptides.; EC=3.4.24.1;
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: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MISCELLANEOUS: The recombinant cysteine-rich domain does not inhibit
CC ADP-induced platelet aggregation (PubMed:10620350) as well as
CC convulxin-induced platelet aggregation, demonstrating no activity on
CC the other collagen receptor GPVI (GP6) (PubMed:12914938).
CC {ECO:0000305|PubMed:10620350, ECO:0000305|PubMed:12914938}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIa sub-subfamily. {ECO:0000305}.
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DR EMBL; U01234; AAA03326.1; -; mRNA.
DR PIR; S41607; S41607.
DR AlphaFoldDB; Q92043; -.
DR SMR; Q92043; -.
DR MEROPS; M12.142; -.
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; 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; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 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 Calcium; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW Metalloprotease; Platelet aggregation inhibiting toxin; Protease; Secreted;
KW Toxin; Zinc.
FT CHAIN 1..>419
FT /note="Zinc metalloproteinase-disintegrin-like atrolysin-A"
FT /id="PRO_5000143927"
FT DOMAIN 6..202
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 210..296
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 274..276
FT /note="D/ECD-tripeptide"
FT ACT_SITE 143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 9
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 215
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 222
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..197
FT /evidence="ECO:0000250"
FT DISULFID 157..181
FT /evidence="ECO:0000250"
FT DISULFID 159..164
FT /evidence="ECO:0000250"
FT DISULFID 213..242
FT /evidence="ECO:0000250"
FT DISULFID 224..237
FT /evidence="ECO:0000250"
FT DISULFID 226..232
FT /evidence="ECO:0000250"
FT DISULFID 236..259
FT /evidence="ECO:0000250"
FT DISULFID 250..256
FT /evidence="ECO:0000250"
FT DISULFID 255..281
FT /evidence="ECO:0000250"
FT DISULFID 268..288
FT /evidence="ECO:0000250"
FT DISULFID 275..307
FT /evidence="ECO:0000250"
FT DISULFID 300..312
FT /evidence="ECO:0000250"
FT DISULFID 319..369
FT /evidence="ECO:0000250"
FT DISULFID 334..376
FT /evidence="ECO:0000250"
FT DISULFID 347..357
FT /evidence="ECO:0000250"
FT DISULFID 364..398
FT /evidence="ECO:0000250"
FT DISULFID 392..403
FT /evidence="ECO:0000250"
FT NON_TER 419
SQ SEQUENCE 419 AA; 46879 MW; 442833518478E416 CRC64;
ERLTKRYVEL VIVADHRMFT KYNGNLKKIR KWIYQIVNTI NEIYIPLNIR VALVRLEIWS
NGDLIDVTSA ANVTLKSFGN WRVTNLLRRK SHDNAQLLTA IDLDEETLGL APLGTMCDPK
LSIGIVQDHS PINLLVAVTM AHELGHNLGM VHDENRCHCS TPACVMCAVL RQRPSYEFSD
CSLNHYRTFI INYNPQCILN EPLQTDIISP PVCGNELLEV GEECDCGSPR TCRDPCCDAA
TCKLHSWVEC ESGECCQQCK FTSAGNVCRP ARSECDIAES CTGQSADCPT DDFHRNGKPC
LHNFGYCYNG NCPIMYHQCY ALWGSNVTVA PDACFDINQS GNNSFYCRKE NGVNIPCAQE
DVKCGRLFCN VNDFLCRHKY SDDGMVDHGT KCADGKVCKN RQCVDVTTAY KSTSGFSQI
