VM2TO_ERIMA
ID VM2TO_ERIMA Reviewed; 49 AA.
AC P0C6S4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 1.
DT 25-MAY-2022, entry version 47.
DE RecName: Full=Disintegrin eristostatin {ECO:0000303|PubMed:8042985};
OS Eristicophis macmahoni (Leaf-nosed viper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Eristicophis.
OX NCBI_TaxID=110227;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8042985; DOI=10.1042/bj3010429;
RA McLane M.A., Kowalska M.A., Silver L., Shattil S.J., Niewiarowski S.;
RT "Interaction of disintegrins with the alpha IIb beta 3 receptor on resting
RT and activated human platelets.";
RL Biochem. J. 301:429-436(1994).
RN [2]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=7538018; DOI=10.3109/15419069409014213;
RA Pfaff M., McLane M.A., Beviglia L., Niewiarowski S., Timpl R.;
RT "Comparison of disintegrins with limited variation in the RGD loop in their
RT binding to purified integrins alpha IIb beta 3, alpha V beta 3 and alpha 5
RT beta 1 and in cell adhesion inhibition.";
RL Cell Adhes. Commun. 2:491-501(1994).
RN [3]
RP FUNCTION ON METASTASIS.
RX PubMed=7641809; DOI=10.1006/excr.1995.1266;
RA Morris V.L., Schmidt E.E., Koop S., MacDonald I.C., Grattan M., Khokha R.,
RA McLane M.A., Niewiarowski S., Chambers A.F., Groom A.C.;
RT "Effects of the disintegrin eristostatin on individual steps of
RT hematogenous metastasis.";
RL Exp. Cell Res. 219:571-578(1995).
RN [4]
RP FUNCTION ON METASTASIS.
RX PubMed=7549046;
RA Beviglia L., Stewart G.J., Niewiarowski S.;
RT "Effect of four disintegrins on the adhesive and metastatic properties of
RT B16F10 melanoma cells in a murine model.";
RL Oncol. Res. 7:7-20(1995).
RN [5]
RP DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=8706902; DOI=10.1016/0014-5793(96)00716-8;
RA McLane M.A., Vijay-Kumar S., Marcinkiewicz C., Calvete J.J.,
RA Niewiarowski S.;
RT "Importance of the structure of the RGD-containing loop in the disintegrins
RT echistatin and eristostatin for recognition of alpha IIb beta 3 and alpha v
RT beta 3 integrins.";
RL FEBS Lett. 391:139-143(1996).
RN [6]
RP FUNCTION ON METASTASIS.
RX PubMed=9457071; DOI=10.1006/excr.1997.3821;
RA Danen E.H., Marcinkiewicz C., Cornelissen I.M., van Kraats A.A.,
RA Pachter J.A., Ruiter D.J., Niewiarowski S., van Muijen G.N.;
RT "The disintegrin eristostatin interferes with integrin alpha 4 beta 1
RT function and with experimental metastasis of human melanoma cells.";
RL Exp. Cell Res. 238:188-196(1998).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF GLN-1; GLU-2; GLU-3; PRO-4; THR-7; ARG-13;
RP LYS-17; ARG-18; LYS-21; VAL-22; ARG-24; VAL-25; ARG-27; GLY-28; ASP-29;
RP TRP-30; ASN-31; ASP-33; SER-39; ASP-41; TRP-47; ASN-48 AND GLY-49.
RC TISSUE=Venom;
RX PubMed=17316731; DOI=10.1016/j.toxicon.2006.12.013;
RA Tian J., Paquette-Straub C., Sage E.H., Funk S.E., Patel V., Galileo D.,
RA McLane M.A.;
RT "Inhibition of melanoma cell motility by the snake venom disintegrin
RT eristostatin.";
RL Toxicon 49:899-908(2007).
CC -!- FUNCTION: Is a potent inhibitor of ADP-induced platelet aggregation.
CC Acts by binding to alpha-IIb/beta-3 (ITGA2B/ITGB3) receptor on the
CC platelet surface. Binds with the same high affinity to resting and
CC activated platelets. Also binds the alpha-4/beta-1 (ITGA4/ITGB1)
CC integrin. Is a potent inhibitor of human and murine melanoma metastases
CC in mouse model systems, also due to the inhibition of binding between
CC the alpha-4/beta-1 integrin and the vascular cell adhesion protein
CC VCAM1. Reacts neither with the integrin alpha-V/beta-3 (ITGAV/ITGB3)
CC vitronectin receptor nor with the integrin alpha-5/beta-1 (ITGA5/ITGB1)
CC fibronectin receptor. Has no effect on cell proliferation or
CC angiogenesis. Specifically inhibits cell migration on fibronectin, but
CC not that on collagen IV or laminin. May involve fibronectin-binding
CC integrins that mediate cell migration. {ECO:0000269|PubMed:17316731,
CC ECO:0000269|PubMed:7538018, ECO:0000269|PubMed:7549046,
CC ECO:0000269|PubMed:7641809, ECO:0000269|PubMed:8042985,
CC ECO:0000269|PubMed:9457071}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8042985}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8042985}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the short disintegrin
CC subfamily. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIa sub-subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0C6S4; -.
DR SMR; P0C6S4; -.
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 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 Cell adhesion impairing toxin; Direct protein sequencing; Disulfide bond;
KW Hemostasis impairing toxin; Platelet aggregation inhibiting toxin;
KW Secreted; Toxin.
FT CHAIN 1..49
FT /note="Disintegrin eristostatin"
FT /evidence="ECO:0000269|PubMed:8042985"
FT /id="PRO_0000326414"
FT DOMAIN 1..49
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 27..29
FT /note="Cell attachment site"
FT DISULFID 5..14
FT /evidence="ECO:0000269|PubMed:8706902"
FT DISULFID 10..35
FT /evidence="ECO:0000269|PubMed:8706902"
FT DISULFID 11..40
FT /evidence="ECO:0000269|PubMed:8706902"
FT DISULFID 23..42
FT /evidence="ECO:0000269|PubMed:8706902"
FT MUTAGEN 1
FT /note="Q->A: No change in inhibition of wound closure and
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 2
FT /note="E->A: Loss of inhibition of wound closure, but no
FT change in platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 3
FT /note="E->A: No change in inhibition of wound closure and
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 4
FT /note="P->A: Only inhibition of platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 7
FT /note="T->A: Loss of inhibition of wound closure, but no
FT change in platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 13
FT /note="R->A: Loss of inhibition of wound closure, but no
FT change in platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 17
FT /note="K->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 18
FT /note="R->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 21
FT /note="K->A: Only inhibition of platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 22
FT /note="V->A: Only inhibition of platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 24
FT /note="R->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 25
FT /note="V->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 27
FT /note="R->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 28
FT /note="G->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 29
FT /note="D->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 30
FT /note="W->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 31
FT /note="N->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 33
FT /note="D->A: No change in inhibition of wound closure and
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 39
FT /note="S->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 41
FT /note="D->A: Loss of inhibition of wound closure, and of
FT platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 47
FT /note="W->A: Loss of inhibition of wound closure, but no
FT change in platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 48
FT /note="N->A: Loss of inhibition of wound closure, but no
FT change in platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
FT MUTAGEN 49
FT /note="G->A: Loss of inhibition of wound closure, but no
FT change in platelet aggregation."
FT /evidence="ECO:0000269|PubMed:17316731"
SQ SEQUENCE 49 AA; 5511 MW; BCFCA3F3C5EDAE5E CRC64;
QEEPCATGPC CRRCKFKRAG KVCRVARGDW NDDYCTGKSC DCPKNPWNG
