3SPM_DENJA
ID 3SPM_DENJA Reviewed; 59 AA.
AC P28375;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Dendroaspin {ECO:0000303|PubMed:16798616, ECO:0000303|PubMed:7634091, ECO:0000303|PubMed:7813476};
DE AltName: Full=Glycoprotein IIb-IIIa antagonist;
DE AltName: Full=Mambin {ECO:0000303|PubMed:1591238};
DE AltName: Full=Platelet aggregation inhibitor;
OS Dendroaspis jamesoni kaimosae (Eastern Jameson's mamba).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX NCBI_TaxID=8619;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1591238; DOI=10.1021/bi00135a004;
RA McDowell R.S., Dennis M.S., Louie A., Shuster M., Mulkerrin M.G.,
RA Lazarus R.A.;
RT "Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation
RT inhibitor structurally related to the short neurotoxins.";
RL Biochemistry 31:4766-4772(1992).
RN [2]
RP MUTAGENESIS OF PRO-42; PRO-47; PRO-49; 42-PRO--PRO-47 AND 47-PRO--PRO-49,
RP AND FUNCTION.
RX PubMed=11311124; DOI=10.1042/bj3550633;
RA Lu X., Sun Y., Shang D., Wattam B., Egglezou S., Hughes T., Hyde E.,
RA Scully M., Kakkar V.;
RT "Evaluation of the role of proline residues flanking the RGD motif of
RT dendroaspin, an inhibitior of platelet aggregation and cell adhesion.";
RL Biochem. J. 355:633-638(2001).
RN [3]
RP MUTAGENESIS OF GLY-44, AND FUNCTION.
RX PubMed=11336631; DOI=10.1042/0264-6021:3560011;
RA Wattam B., Shang D., Rahman S., Egglezou S., Scully M., Kakkar V., Lu X.;
RT "Arg-Tyr-Asp (RYD) and Arg-Cys-Asp (RCD) motifs in dendroaspin promote
RT selective inhibition of beta1 and beta3 integrins.";
RL Biochem. J. 356:11-17(2001).
RN [4]
RP MUTAGENESIS OF ARG-43, AND FUNCTION.
RX PubMed=16798616; DOI=10.1080/15419060600726183;
RA Lu X., Davies J., Lu D., Xia M., Wattam B., Shang D., Sun Y., Scully M.,
RA Kakkar V.;
RT "The effect of the single substitution of arginine within the RGD
RT tripeptide motif of a modified neurotoxin dendroaspin on its activity of
RT platelet aggregation and cell adhesion.";
RL Cell Commun. Adhes. 13:171-183(2006).
RN [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7634091; DOI=10.1038/nsb1194-802;
RA Sutcliffe M.J., Jaseja M., Hyde E.I., Lu X., Williams J.A.;
RT "Three-dimensional structure of the RGD-containing neurotoxin homologue
RT dendroaspin.";
RL Nat. Struct. Biol. 1:802-807(1994).
RN [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7813476; DOI=10.1111/j.1432-1033.1994.00861.x;
RA Jaseja M., Lu X., Williams J.A., Sutcliffe M.J., Kakkar V.V., Parslow R.A.,
RA Hyde E.I.;
RT "1H-NMR assignments and secondary structure of dendroaspin, an RGD-
RT containing glycoprotein IIb-IIIa (alpha IIb-beta 3) antagonist with a
RT neurotoxin fold.";
RL Eur. J. Biochem. 226:861-868(1994).
CC -!- FUNCTION: Inhibits ADP-induced platelet aggregation and inhibits the
CC binding of purified platelet fibrinogen receptor alpha-IIb/beta-3
CC (ITGA2B/ITGB3) to immobilized fibrinogen (PubMed:1591238). Has also
CC been described to inhibit cell adhesion to fibrinogen, fibronectin,
CC laminin and collagen (PubMed:16798616, PubMed:11336631).
CC {ECO:0000269|PubMed:11336631, ECO:0000269|PubMed:1591238,
CC ECO:0000269|PubMed:16798616}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1591238}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Antiplatelet toxin sub-subfamily. {ECO:0000305}.
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DR PIR; A42561; T6EP5J.
DR PDB; 1DRS; NMR; -; A=1-59.
DR PDB; 2LA1; NMR; -; A=1-59.
DR PDBsum; 1DRS; -.
DR PDBsum; 2LA1; -.
DR AlphaFoldDB; P28375; -.
DR BMRB; P28375; -.
DR SMR; P28375; -.
DR EvolutionaryTrace; P28375; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR SUPFAM; SSF57302; SSF57302; 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..59
FT /note="Dendroaspin"
FT /evidence="ECO:0000269|PubMed:1591238"
FT /id="PRO_0000093659"
FT MOTIF 43..45
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT DISULFID 3..22
FT /evidence="ECO:0000269|PubMed:7634091,
FT ECO:0000269|PubMed:7813476, ECO:0000312|PDB:1DRS,
FT ECO:0000312|PDB:2LA1"
FT DISULFID 17..37
FT /evidence="ECO:0000269|PubMed:7634091,
FT ECO:0000269|PubMed:7813476, ECO:0000312|PDB:1DRS,
FT ECO:0000312|PDB:2LA1"
FT DISULFID 39..51
FT /evidence="ECO:0000269|PubMed:7634091,
FT ECO:0000269|PubMed:7813476, ECO:0000312|PDB:1DRS,
FT ECO:0000312|PDB:2LA1"
FT DISULFID 52..57
FT /evidence="ECO:0000269|PubMed:7634091,
FT ECO:0000269|PubMed:7813476, ECO:0000312|PDB:1DRS,
FT ECO:0000312|PDB:2LA1"
FT MUTAGEN 42..47
FT /note="PRGDMP->ARGDMA: 7-fold loss of ability to inhibit
FT ADP-induced platelet aggregation."
FT /evidence="ECO:0000269|PubMed:11311124"
FT MUTAGEN 42
FT /note="P->A: No change in ability to inhibit ADP-induced
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:11311124"
FT MUTAGEN 43
FT /note="R->A: This mutation alters integrin binding
FT selectivity. It provokes 95-fold loss of ability to inhibit
FT ADP-induced platelet aggregation, 71-fold loss of ability
FT to inhibit A375 cell adhesion to fibrinogen, and almost
FT complete loss of ability to inhibit HEL cell adhesion to
FT fibrinogen."
FT /evidence="ECO:0000269|PubMed:16798616"
FT MUTAGEN 43
FT /note="R->H: This mutation alters integrin binding
FT selectivity. It provokes 14-fold loss of ability to inhibit
FT ADP-induced platelet aggregation, 3-fold loss of ability to
FT inhibit A375 cell adhesion to fibrinogen, 8-fold loss of
FT ability to inhibit HEL cell adhesion to fibrinogen."
FT /evidence="ECO:0000269|PubMed:16798616"
FT MUTAGEN 43
FT /note="R->K: This mutation alters integrin binding
FT selectivity. It provokes 1.4-fold loss of ability to
FT inhibit ADP-induced platelet aggregation, 6-fold loss of
FT ability to inhibit A375 cell adhesion to fibrinogen and 8-
FT fold loss of ability to inhibit HEL cell adhesion to
FT fibrinogen."
FT /evidence="ECO:0000269|PubMed:16798616"
FT MUTAGEN 43
FT /note="R->Q: This mutation alters integrin binding
FT selectivity. It provokes 33-fold loss of ability to inhibit
FT ADP-induced platelet aggregation, 5-fold loss of ability to
FT inhibit A375 cell adhesion to fibrinogen, and almost
FT complete loss of ability to inhibit HEL cell adhesion to
FT fibrinogen."
FT /evidence="ECO:0000269|PubMed:16798616"
FT MUTAGEN 44
FT /note="G->C: This mutation promotes selective inhibition of
FT beta-3 integrin; it provokes 1.8-fold loss of ability to
FT inhibit ADP-induced platelet aggregation, 6-fold loss of
FT ability to inhibit A375 cell adhesion to fibrinogen and
FT 330-fold loss of ability to inhibit K562 cell adhesion to
FT fibrinogen."
FT /evidence="ECO:0000269|PubMed:11336631"
FT MUTAGEN 44
FT /note="G->Y: This mutation promotes selective inhibition of
FT beta-1 integrin; provokes 1.2-fold loss of ability to
FT inhibit ADP-induced platelet aggregation, 11-fold loss of
FT ability to inhibit A375 cell adhesion to fibrinogen and 75-
FT fold loss of ability to inhibit K562 cell adhesion to
FT fibrinogen."
FT /evidence="ECO:0000269|PubMed:11336631"
FT MUTAGEN 47..49
FT /note="PGP->AGA: 8.5-fold loss of ability to inhibit ADP-
FT induced platelet aggregation."
FT /evidence="ECO:0000269|PubMed:11311124"
FT MUTAGEN 47
FT /note="P->A: No change in ability to inhibit ADP-induced
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:11311124"
FT MUTAGEN 49
FT /note="P->A: No change in ability to inhibit ADP-induced
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:11311124"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:1DRS"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:1DRS"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1DRS"
FT TURN 28..31
FT /evidence="ECO:0007829|PDB:1DRS"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:2LA1"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:1DRS"
SQ SEQUENCE 59 AA; 6754 MW; 20DDC6A5D9DF9E41 CRC64;
RICYNHLGTK PPTTETCQED SCYKNIWTFD NIIRRGCGCF TPRGDMPGPY CCESDKCNL
