ID   VM2CO_AGKCO             Reviewed;         483 AA.
AC   Q9IAB0;
DT   07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 98.
DE   RecName: Full=Zinc metalloproteinase/disintegrin;
DE   Contains:
DE     RecName: Full=Snake venom metalloproteinase;
DE              Short=SVMP;
DE              EC=3.4.24.-;
DE   Contains:
DE     RecName: Full=Disintegrin contortrostatin;
DE   Flags: Precursor;
OS   Agkistrodon contortrix contortrix (Southern copperhead).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX   NCBI_TaxID=8713 {ECO:0000312|EMBL:AAF65171.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 419-433, FUNCTION, AND
RP   SUBUNIT.
RC   TISSUE=Venom, and Venom gland {ECO:0000269|PubMed:10700384};
RX   PubMed=10700384; DOI=10.1006/abbi.1999.1682;
RA   Zhou Q., Hu P., Ritter M.R., Swenson S.D., Argounova S., Epstein A.L.,
RA   Markland F.S.;
RT   "Molecular cloning and functional expression of contortrostatin, a
RT   homodimeric disintegrin from southern copperhead snake venom.";
RL   Arch. Biochem. Biophys. 375:278-288(2000).
CC   -!- FUNCTION: [Snake venom metalloproteinase]: Impairs hemostasis in the
CC       envenomed animal (By similarity). This product has not been identified
CC       in the venom. {ECO:0000250, ECO:0000269|PubMed:10700384}.
CC   -!- FUNCTION: [Disintegrin contortrostatin]: Inhibits ADP-induced platelet
CC       aggregation. Binds and inhibits integrins GPIIb/GPIIIa (ITGA2B/ITGB3),
CC       alpha-5/beta-1 (ITGA5/ITGB1), alpha-V/beta-3 (ITGAV/ITGB3), and alpha-
CC       V/beta-5 (ITGAV/ITGB5). It blocks cancer cell adhesion to fibronectin
CC       and vitronectin and thus prevents invasion of cancer cells.
CC       {ECO:0000269|PubMed:10700384}.
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: Homodimer; disulfide-linked (disintegrin).
CC       {ECO:0000269|PubMed:10700384}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- MISCELLANEOUS: The disintegrin belongs to the dimeric disintegrin
CC       subfamily.
CC   -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC       subfamily. P-IId sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF212305; AAF65171.1; -; mRNA.
DR   AlphaFoldDB; Q9IAB0; -.
DR   SMR; Q9IAB0; -.
DR   MEROPS; M12.178; -.
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; 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; PF00200; Disintegrin; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   PRINTS; PR00289; DISINTEGRIN.
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; Cell adhesion impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW   Metalloprotease; Platelet aggregation inhibiting toxin; Protease; Secreted;
KW   Signal; Toxin; Zinc; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..190
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028961"
FT   CHAIN           191..394
FT                   /note="Snake venom metalloproteinase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028962"
FT   PROPEP          395..418
FT                   /evidence="ECO:0000269|PubMed:10700384"
FT                   /id="PRO_0000028963"
FT   CHAIN           419..483
FT                   /note="Disintegrin contortrostatin"
FT                   /evidence="ECO:0000269|PubMed:10700384"
FT                   /id="PRO_0000028964"
FT   DOMAIN          198..394
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          402..483
FT                   /note="Disintegrin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   MOTIF           461..463
FT                   /note="Cell attachment site"
FT   ACT_SITE        335
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                   /evidence="ECO:0000250"
FT   BINDING         285
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   BINDING         334
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
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         344
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         389
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   BINDING         392
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   DISULFID        309..389
FT                   /evidence="ECO:0000250"
FT   DISULFID        349..373
FT                   /evidence="ECO:0000250"
FT   DISULFID        351..356
FT                   /evidence="ECO:0000250"
FT   DISULFID        425..448
FT                   /evidence="ECO:0000250|UniProtKB:P18619"
FT   DISULFID        439..445
FT                   /evidence="ECO:0000250|UniProtKB:P18619"
FT   DISULFID        444..469
FT                   /evidence="ECO:0000250|UniProtKB:P18619"
FT   DISULFID        457..476
FT                   /evidence="ECO:0000250|UniProtKB:P18619"
SQ   SEQUENCE   483 AA;  53948 MW;  2DBB370FDC590007 CRC64;
     MIQVLLVTLC LAAFPYQGSS IILESGNVND YEVLYPQKVT ALPKGAVQPK YEDTMQYEFK
     VNGEPVVLHL EKNKGLFSKD YSETHYSSDG RKITTNPPVE DHCYYHGRIQ NDADSTASIS
     ACNGLKGHFK LQGETYLIEP LKLSDSEAHA VYKYENVEKE DEAPKMCGVT QTNWESDEPI
     KKASQLNLTP EQQGFPQRYI ELVVVADHRM FTKYNGNLNT IRIWVHELVN TMNVFYRPLN
     IRVSLTDLEV WSDQDLINVQ PAAADTLEAF GDWRETVLLN RISHDNAQLL TAIELDGETI
     GLANRGTMCD PKLSTGIVQD HSAINLWVAV TMAHEMGHNL GISHDGNQCH CDANSCIMSE
     ELREQLSFEF SDCSQNQYQT YLTDHNPQCM LNEPLRTDIV STPVSGNELL ETGEESDFDA
     PANPCCDAAT CKLTTGSQCA DGLCCDQCKF MKEGTVCRRA RGDDLDDYCN GISAGCPRNP
     FHA