ID   VM2RH_CALRH             Reviewed;         478 AA.
AC   P30403; P17494;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 2.
DT   02-SEP-2026, entry version 151.
DE   RecName: Full=Zinc metalloproteinase/disintegrin;
DE   Contains:
DE     RecName: Full=Snake venom metalloproteinase rhodostoxin {ECO:0000303|PubMed:8561498};
DE              Short=SVMP;
DE              EC=3.4.24.-;
DE     AltName: Full=Hemorrhagic protein {ECO:0000303|PubMed:8561498};
DE   Contains:
DE     RecName: Full=Disintegrin rhodostomin {ECO:0000303|PubMed:1755841, ECO:0000303|PubMed:7916592};
DE              Short=RHO;
DE              Short=RHOD;
DE     AltName: Full=Disintegrin kistrin {ECO:0000303|PubMed:1734953};
DE     AltName: Full=Platelet aggregation activation inhibitor;
DE   Flags: Precursor;
OS   Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Calloselasma.
OX   NCBI_TaxID=8717;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=7916635; DOI=10.1016/0167-4781(93)90190-o;
RA   Au L.-C.;
RT   "Nucleotide sequence of a full-length cDNA encoding a common precursor of
RT   platelet aggregation inhibitor and hemorrhagic protein from Calloselasma
RT   rhodostoma venom.";
RL   Biochim. Biophys. Acta 1173:243-245(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 77-478.
RC   TISSUE=Venom gland;
RX   PubMed=1755841; DOI=10.1016/0006-291x(91)91230-a;
RA   Au L.-C., Huang Y.-B., Huang T.-F., Teh G.-W., Lin H.-H., Choo K.-B.;
RT   "A common precursor for a putative hemorrhagic protein and rhodostomin, a
RT   platelet aggregation inhibitor of the venom of Calloselasma rhodostoma:
RT   molecular cloning and sequence analysis.";
RL   Biochem. Biophys. Res. Commun. 181:585-593(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 408-475.
RC   TISSUE=Venom gland;
RX   PubMed=7916592; DOI=10.1006/bbrc.1993.1037;
RA   Chang H.H., Hu S.T., Huang T.-F., Chen S.H., Lee Y.H., Lo S.J.;
RT   "Rhodostomin, an RGD-containing peptide expressed from a synthetic gene in
RT   Escherichia coli, facilitates the attachment of human hepatoma cells.";
RL   Biochem. Biophys. Res. Commun. 190:242-249(1993).
RN   [4]
RP   PROTEIN SEQUENCE OF 189-391, DISULFIDE BONDS, GLYCOSYLATION AT ASN-279 AND
RP   ASN-369, GLYCAN STRUCTURE, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=8561498; DOI=10.1006/abbi.1996.0025;
RA   Chung M.C., Ponnudurai G., Kataoka M., Shimizu S., Tan N.H.;
RT   "Structural studies of a major hemorrhagin (rhodostoxin) from the venom of
RT   Calloselasma rhodostoma (Malayan pit viper).";
RL   Arch. Biochem. Biophys. 325:199-208(1996).
RN   [5]
RP   PROTEIN SEQUENCE OF 408-475, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=2236100; DOI=10.3181/00379727-195-43129b;
RA   Gould R.J., Polokoff M.A., Friedman P.A., Huang T.-F., Holt J.C.,
RA   Cook J.J., Niecviarowski S.;
RT   "Disintegrins: a family of integrin inhibitory proteins from viper
RT   venoms.";
RL   Proc. Soc. Exp. Biol. Med. 195:168-171(1990).
RN   [6]
RP   PROTEIN SEQUENCE OF 408-475, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=2320569; DOI=10.1073/pnas.87.7.2471;
RA   Dennis M.S., Henzel W.J., Pitti R.M., Lipari M.T., Napier M.A.,
RA   Deisher T.A., Bunting S., Lazarus R.A.;
RT   "Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms:
RT   evidence for a family of platelet-aggregation inhibitors.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:2471-2475(1990).
RN   [7]
RP   STRUCTURE BY NMR OF 408-475.
RX   PubMed=8418848; DOI=10.1021/bi00052a036;
RA   Adler M., Carter P., Lazarus R.A., Wagner G.;
RT   "Cysteine pairing in the glycoprotein IIbIIIa antagonist kistrin using NMR,
RT   chemical analysis, and structure calculations.";
RL   Biochemistry 32:282-289(1993).
RN   [8] {ECO:0000312|PDB:1N4Y}
RP   STRUCTURE BY NMR OF 408-475, AND DISULFIDE BONDS.
RX   PubMed=1862345; DOI=10.1126/science.1862345;
RA   Adler M., Lazarus R.A., Dennis M.S., Wagner G.;
RT   "Solution structure of kistrin, a potent platelet aggregation inhibitor and
RT   GP IIb-IIIa antagonist.";
RL   Science 253:445-448(1991).
RN   [9]
RP   STRUCTURE BY NMR OF 408-475.
RX   PubMed=1734953; DOI=10.1021/bi00119a011;
RA   Adler M., Wagner G.;
RT   "Sequential 1H NMR assignments of kistrin, a potent platelet aggregation
RT   inhibitor and glycoprotein IIb-IIIa antagonist.";
RL   Biochemistry 31:1031-1039(1992).
CC   -!- FUNCTION: [Snake venom metalloproteinase rhodostoxin]: Impairs
CC       hemostasis in the envenomed animal. {ECO:0000250}.
CC   -!- FUNCTION: [Disintegrin rhodostomin]: Inhibits platelet aggregation
CC       induced by ADP, thrombin, platelet-activating factor and collagen. Acts
CC       by inhibiting fibrinogen interaction with platelet receptors alpha-
CC       IIb/beta-3 (ITGA2B/ITGB3).
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: Monomeric (disintegrin). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Snake venom metalloproteinase rhodostoxin]:
CC       Secreted {ECO:0000269|PubMed:2236100, ECO:0000269|PubMed:2320569,
CC       ECO:0000269|PubMed:8561498}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:2236100, ECO:0000305|PubMed:2320569,
CC       ECO:0000305|PubMed:8561498}.
CC   -!- PTM: Glycans are composed of 4 GlcNAc, 3 Man, 2 Gal, 2 NeuAC and 1 Fuc
CC       residue. {ECO:0000269|PubMed:8561498}.
CC   -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC       subfamily. P-IIa sub-subfamily. {ECO:0000305}.
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DR   EMBL; L08780; AAA49196.1; -; mRNA.
DR   PIR; S33792; JQ1301.
DR   PDB; 1N4Y; NMR; -; A=408-475.
DR   PDB; 1Q7I; NMR; -; A=408-475.
DR   PDB; 1Q7J; NMR; -; A=408-475.
DR   PDB; 2LJV; NMR; -; A=408-475.
DR   PDB; 2M75; NMR; -; A=408-475.
DR   PDB; 2M7F; NMR; -; A=408-478.
DR   PDB; 2M7H; NMR; -; A=408-478.
DR   PDB; 2PJF; NMR; -; A=408-475.
DR   PDB; 2PJG; NMR; -; A=408-475.
DR   PDB; 2PJI; NMR; -; A=408-475.
DR   PDB; 3UCI; X-ray; 1.35 A; A=408-475.
DR   PDB; 4M4C; X-ray; 1.80 A; A/B/C/D=408-475.
DR   PDB; 4R5R; X-ray; 0.96 A; A/B=408-475.
DR   PDB; 4R5U; X-ray; 1.81 A; A/B=408-475.
DR   PDB; 4RQG; X-ray; 1.66 A; A/B=408-475.
DR   PDB; 7X4S; X-ray; 1.80 A; A/B=408-475.
DR   PDB; 7X4V; X-ray; 1.38 A; A/B=408-475.
DR   PDB; 7X4Z; X-ray; 1.48 A; A/B=408-475.
DR   PDB; 9IUJ; EM; 2.78 A; C=408-475.
DR   AlphaFoldDB; P30403; -.
DR   BMRB; P30403; -.
DR   EMDB; EMD-60907; -.
DR   MDposit; P30403; -.
DR   SMR; P30403; -.
DR   MEROPS; M12.161; -.
DR   iPTMnet; P30403; -.
DR   EvolutionaryTrace; P30403; -.
DR   GO; GO:0005576; C:extracellular region; EXP:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:TreeGrafter.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR   FunFam; 3.40.390.10:FF:000002; Disintegrin and metalloproteinase domain-containing protein 22; 1.
DR   FunFam; 4.10.70.10:FF:000005; Zinc metalloproteinase/disintegrin; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 4.10.70.10; Disintegrin domain; 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   PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1.
DR   PANTHER; PTHR11905:SF32; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 28; 1.
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; Blood coagulation inhibitor (disintegrin); 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 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.
DR   PDBsum; 1N4Y; -.
DR   PDBsum; 1Q7I; -.
DR   PDBsum; 1Q7J; -.
DR   PDBsum; 2LJV; -.
DR   PDBsum; 2M75; -.
DR   PDBsum; 2M7F; -.
DR   PDBsum; 2M7H; -.
DR   PDBsum; 2PJF; -.
DR   PDBsum; 2PJG; -.
DR   PDBsum; 2PJI; -.
DR   PDBsum; 3UCI; -.
DR   PDBsum; 4M4C; -.
DR   PDBsum; 4R5R; -.
DR   PDBsum; 4R5U; -.
DR   PDBsum; 4RQG; -.
DR   PDBsum; 7X4S; -.
DR   PDBsum; 7X4V; -.
DR   PDBsum; 7X4Z; -.
DR   PDBsum; 9IUJ; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cell adhesion impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Hemostasis impairing toxin; Hydrolase;
KW   Metal-binding; Metalloprotease; Platelet aggregation inhibiting toxin;
KW   Protease; Secreted; Signal; Toxin; Zinc; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..188
FT                   /evidence="ECO:0000305|PubMed:8561498"
FT                   /id="PRO_0000028956"
FT   CHAIN           189..391
FT                   /note="Snake venom metalloproteinase rhodostoxin"
FT                   /evidence="ECO:0000269|PubMed:8561498"
FT                   /id="PRO_0000028957"
FT   PROPEP          392..407
FT                   /id="PRO_0000028958"
FT   CHAIN           408..475
FT                   /note="Disintegrin rhodostomin"
FT                   /evidence="ECO:0000269|PubMed:2236100,
FT                   ECO:0000269|PubMed:2320569"
FT                   /id="PRO_0000028959"
FT   PROPEP          476..478
FT                   /id="PRO_0000028960"
FT   DOMAIN          194..391
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          397..478
FT                   /note="Disintegrin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   MOTIF           456..458
FT                   /note="Cell attachment site"
FT   ACT_SITE        331
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   BINDING         330
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   BINDING         334
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   BINDING         340
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8561498"
FT   CARBOHYD        369
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8561498"
FT   DISULFID        207..248
FT                   /evidence="ECO:0000305"
FT   DISULFID        305..386
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DISULFID        345..370
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DISULFID        347..353
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DISULFID        411..426
FT                   /evidence="ECO:0000269|PubMed:1862345,
FT                   ECO:0007744|PDB:1N4Y"
FT   DISULFID        413..421
FT                   /evidence="ECO:0000269|PubMed:1862345,
FT                   ECO:0007744|PDB:1N4Y"
FT   DISULFID        420..443
FT                   /evidence="ECO:0000269|PubMed:1862345,
FT                   ECO:0007744|PDB:1N4Y"
FT   DISULFID        434..440
FT                   /evidence="ECO:0000269|PubMed:1862345,
FT                   ECO:0007744|PDB:1N4Y"
FT   DISULFID        439..464
FT                   /evidence="ECO:0000269|PubMed:1862345,
FT                   ECO:0007744|PDB:1N4Y"
FT   DISULFID        452..471
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT                   ECO:0000269|PubMed:1862345, ECO:0007744|PDB:1N4Y"
FT   CONFLICT        287
FT                   /note="M -> T (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           408..410
FT                   /evidence="ECO:0007829|PDB:3UCI"
FT   STRAND          412..415
FT                   /evidence="ECO:0007829|PDB:7X4V"
FT   STRAND          419..421
FT                   /evidence="ECO:0007829|PDB:1N4Y"
FT   TURN            423..425
FT                   /evidence="ECO:0007829|PDB:4R5R"
FT   STRAND          426..428
FT                   /evidence="ECO:0007829|PDB:4R5R"
FT   STRAND          429..431
FT                   /evidence="ECO:0007829|PDB:2PJI"
FT   STRAND          435..437
FT                   /evidence="ECO:0007829|PDB:4R5R"
FT   STRAND          438..441
FT                   /evidence="ECO:0007829|PDB:1Q7I"
FT   STRAND          451..453
FT                   /evidence="ECO:0007829|PDB:4R5R"
FT   STRAND          456..458
FT                   /evidence="ECO:0007829|PDB:4R5R"
FT   HELIX           459..461
FT                   /evidence="ECO:0007829|PDB:4R5R"
FT   STRAND          462..464
FT                   /evidence="ECO:0007829|PDB:1Q7J"
FT   STRAND          466..470
FT                   /evidence="ECO:0007829|PDB:9IUJ"
FT   HELIX           472..474
FT                   /evidence="ECO:0007829|PDB:7X4V"
SQ   SEQUENCE   478 AA;  54006 MW;  6490A2B171D3A830 CRC64;
     MIQVLLVTIC LAAFPYQGSS IILESGNVND YEVVYPRKVI ALSEGAAQQK YEDTMQYEFK
     VNGEPVVLHL EKNKGLFAKD YSETHYSPDG TRITTYPSVE DHCYYQGRIH NDADSTASIS
     ACNGLKGHFK LQGETYFIEP MKLPDSEAHA VFKYENIEKE DESPKMCGVT ETNWESDEPI
     KKVSQLNLNH EIKRHVDIVV VVDSRFCTKH SNDLEVIRKF VHEVVNAIIE SYKYMHFGIS
     LVNLETWCNG DLINVQEDSY ETLKAFGKWR ESDLIKHVNH SNAQFLMDMK FIKNIIGKAY
     LDSICDPERS VGIVQNYHGI TLNVAAIMAH EMGHNLGVRH DGEYCTCYGS SECIMSSHIS
     DPPSKYFSNC SYYQFWKYIE NQNPQCILNK PLRTVSIPVS GNEHLEAGKE CDCSSPENPC
     CDAATCKLRP GAQCGEGLCC EQCKFSRAGK ICRIPRGDMP DDRCTGQSAD CPRYHSHA
//