VM2_BITAR
ID VM2_BITAR Reviewed; 83 AA.
AC P17497; Q4JCS2;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Disintegrin bitistatin {ECO:0000303|PubMed:25363287, ECO:0000303|PubMed:2600082, ECO:0000303|PubMed:9369214};
DE AltName: Full=Arietin {ECO:0000303|PubMed:2043663, ECO:0000303|PubMed:2043664};
DE AltName: Full=Bitan-alpha {ECO:0000303|PubMed:2320569};
DE AltName: Full=Bitistatin D1 {ECO:0000303|PubMed:16786436};
DE AltName: Full=Platelet aggregation activation inhibitor;
DE AltName: Full=Venom protein CM-2 {ECO:0000303|PubMed:7141413};
OS Bitis arietans (African puff adder).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Bitis.
OX NCBI_TaxID=8692;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2600082; DOI=10.1016/s0021-9258(20)88220-9;
RA Shebuski R.J., Ramjit D.R., Bencen G.H., Polokoff M.A.;
RT "Characterization and platelet inhibitory activity of bitistatin, a potent
RT arginine-glycine-aspartic acid-containing peptide from the venom of the
RT viper Bitis arietans.";
RL J. Biol. Chem. 264:21550-21556(1989).
RN [2]
RP PROTEIN SEQUENCE.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=16786436; DOI=10.1007/s00239-005-0268-z;
RA Juarez P., Wagstaff S.C., Oliver J., Sanz L., Harrison R.A., Calvete J.J.;
RT "Molecular cloning of disintegrin-like transcript BA-5A from a Bitis
RT arietans venom gland cDNA library: a putative intermediate in the evolution
RT of the long-chain disintegrin bitistatin.";
RL J. Mol. Evol. 63:142-152(2006).
RN [4]
RP PRELIMINARY PROTEIN SEQUENCE.
RC TISSUE=Venom;
RX PubMed=7141413; DOI=10.1515/bchm2.1982.363.2.1087;
RA Joubert F.J., Haylett T., Strydom D.J., Taljaard N.;
RT "Snake venom: protein CM-2 from Bitis arietans (puff adder) venom.";
RL Hoppe-Seyler's Z. Physiol. Chem. 363:1087-1096(1982).
RN [5]
RP PROTEIN SEQUENCE OF 1-17 AND 56-70.
RC TISSUE=Venom;
RX PubMed=2043663; DOI=10.1016/0304-4165(91)90052-i;
RA Huang T.-F., Wang W.J., Teng C.-M., Liu C.-S., Ouyang C.;
RT "Purification and characterization of an antiplatelet peptide, arietin,
RT from Bitis arietans venom.";
RL Biochim. Biophys. Acta 1074:136-143(1991).
RN [6]
RP MECHANISM OF ACTION.
RX PubMed=2043664; DOI=10.1016/0304-4165(91)90053-j;
RA Huang T.-F., Wang W.J., Teng C.-M., Ouyang C.;
RT "Mechanism of action of the antiplatelet peptide, arietin, from Bitis
RT arietans venom.";
RL Biochim. Biophys. Acta 1074:144-150(1991).
RN [7]
RP DISULFIDE BONDS OF FORM A.
RX PubMed=9369214; DOI=10.1016/s0014-5793(97)01203-9;
RA Calvete J.J., Schrader M., Raida M., McLane M.A., Romero A.,
RA Niewiarowski S.;
RT "The disulphide bond pattern of bitistatin, a disintegrin isolated from the
RT venom of the viper Bitis arietans.";
RL FEBS Lett. 416:197-202(1997).
RN [8]
RP STRUCTURE BY NMR OF FORMS A AND B, DISULFIDE BOND OF FORM A, AND DISULFIDE
RP BOND OF FORM B.
RX PubMed=25363287; DOI=10.1111/febs.13138;
RA Carbajo R.J., Sanz L., Perez A., Calvete J.J.;
RT "NMR structure of bitistatin - a missing piece in the evolutionary pathway
RT of snake venom disintegrins.";
RL FEBS J. 282:341-360(2015).
CC -!- FUNCTION: Inhibits fibrinogen interaction with platelets. Acts by
CC binding to alpha-IIb/beta-3 (ITGA2B/ITGB3) on the platelet surface and
CC inhibits aggregation induced by ADP, thrombin, platelet-activating
CC factor and collagen. {ECO:0000269|PubMed:2600082}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:2600082}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2600082}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2600082}.
CC -!- PTM: Exists in 3 forms in the venom. The forms A, B, and C are present
CC at 53%, 32% and 15%. The forms A and B differ by their disulfide bond
CC pattern in the N-terminal part. No information is known about form C.
CC {ECO:0000269|PubMed:25363287}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the long disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIa sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY924402; AAY43681.1; -; mRNA.
DR PIR; A34156; A34156.
DR PIR; F35982; F35982.
DR PIR; S15982; S15982.
DR PDB; 2MOP; NMR; -; 1=1-83.
DR PDB; 2MP5; NMR; -; 1=1-83.
DR PDBsum; 2MOP; -.
DR PDBsum; 2MP5; -.
DR AlphaFoldDB; P17497; -.
DR BMRB; P17497; -.
DR SMR; P17497; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR Pfam; PF00200; Disintegrin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion impairing toxin; Direct protein sequencing;
KW Disulfide bond; Hemostasis impairing toxin;
KW Platelet aggregation inhibiting toxin; Secreted; Toxin.
FT CHAIN 1..83
FT /note="Disintegrin bitistatin"
FT /evidence="ECO:0000269|PubMed:2320569,
FT ECO:0000269|PubMed:2600082"
FT /id="PRO_0000101784"
FT DOMAIN 2..83
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 64..66
FT /note="Cell attachment site"
FT DISULFID 5..34
FT /note="In form B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000312|PDB:2MP5"
FT DISULFID 5..24
FT /note="In form A"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MP5"
FT DISULFID 16..34
FT /note="In form A"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MP5"
FT DISULFID 16..29
FT /note="In form B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000312|PDB:2MP5"
FT DISULFID 18..29
FT /note="In form A"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MP5"
FT DISULFID 18..24
FT /note="In form B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000312|PDB:2MP5"
FT DISULFID 28..51
FT /note="In forms A and B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MOP,
FT ECO:0000312|PDB:2MP5"
FT DISULFID 42..48
FT /note="In form A and B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MOP,
FT ECO:0000312|PDB:2MP5"
FT DISULFID 47..72
FT /note="In form A and B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MOP,
FT ECO:0000312|PDB:2MP5"
FT DISULFID 60..79
FT /note="In form A and B"
FT /evidence="ECO:0000269|PubMed:25363287,
FT ECO:0000269|PubMed:9369214, ECO:0000312|PDB:2MOP,
FT ECO:0000312|PDB:2MP5"
FT CONFLICT 57
FT /note="G -> L (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="W -> S (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:2MOP"
FT TURN 21..25
FT /evidence="ECO:0007829|PDB:2MOP"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:2MOP"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:2MOP"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:2MOP"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2MOP"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:2MOP"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:2MOP"
SQ SEQUENCE 83 AA; 9004 MW; EE3406FF9B757E92 CRC64;
SPPVCGNKIL EQGEDCDCGS PANCQDRCCN AATCKLTPGS QCNYGECCDQ CRFKKAGTVC
RIARGDWNDD YCTGKSSDCP WNH
