VM2_BOTAL
ID VM2_BOTAL Reviewed; 78 AA.
AC Q801Z4;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2013, sequence version 2.
DT 25-MAY-2022, entry version 61.
DE RecName: Full=Disintegrin DisBa-01;
OS Bothrops alternatus (Urutu) (Rhinocerophis alternatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=64174;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION ON ITGAV/ITGB3, 3D-STRUCTURE MODELING
RP IN COMPLEX WITH ALPHA-5/BETA-3 (ITGAV/ITGB3), AND SITES ARG-52; ARG-55;
RP ASP-57; ARG-72; PHE-75 AND HIS-76.
RC TISSUE=Venom gland;
RX PubMed=17952617; DOI=10.1007/s10585-007-9101-y;
RA Ramos O.H., Kauskot A., Cominetti M.R., Bechyne I., Salla Pontes C.L.,
RA Chareyre F., Manent J., Vassy R., Giovannini M., Legrand C.,
RA Selistre-de-Araujo H.S., Crepin M., Bonnefoy A.;
RT "A novel alpha(v)beta (3)-blocking disintegrin containing the RGD motive,
RT DisBa-01, inhibits bFGF-induced angiogenesis and melanoma metastasis.";
RL Clin. Exp. Metastasis 25:53-64(2008).
RN [2]
RP FUNCTION ON ITGA2B/ITGB3.
RX PubMed=18508682; DOI=10.2741/3176;
RA Kauskot A., Cominetti M.R., Ramos O.H., Bechyne I., Renard J.M.,
RA Hoylaerts M.F., Crepin M., Legrand C., Selistre-de-Araujo H.S.,
RA Bonnefoy A.;
RT "Hemostatic effects of recombinant DisBa-01, a disintegrin from Bothrops
RT alternatus.";
RL Front. Biosci. 13:6604-6616(2008).
RN [3]
RP FUNCTION, AND REVIEW.
RX PubMed=22069567; DOI=10.3390/toxins2112606;
RA Selistre-de-Araujo H.S., Pontes C.L., Montenegro C.F., Martin A.C.;
RT "Snake venom disintegrins and cell migration.";
RL Toxins 2:2606-2621(2010).
RN [4]
RP FUNCTION IN TUMOR MICROENVIRONMENT.
RX PubMed=22561350; DOI=10.1016/j.biochi.2012.04.020;
RA Montenegro C.F., Salla-Pontes C.L., Ribeiro J.U., Machado A.Z., Ramos R.F.,
RA Figueiredo C.C., Morandi V., Selistre-de-Araujo H.S.;
RT "Blocking alphavbeta3 integrin by a recombinant RGD disintegrin impairs
RT VEGF signaling in endothelial cells.";
RL Biochimie 94:1812-1820(2012).
CC -!- FUNCTION: This recombinant disintegrin antagonizes integrins alpha-
CC IIb/beta-3 (ITGA2B/ITGB3) and alpha-V/beta-3 (ITGAV/ITGB3). On
CC ITGA2B/ITGB3, it interferes with the outside/-in phosphorylation of the
CC focal adhesion kinase (PTK2 / FAK) downstream of the integrin. It
CC strongly inhibits platelet aggregation induced by ADP, thrombin, and
CC collagen, abolishes and reverses dynamic platelet recruitment to
CC immobilized fibrinogen. In vivo, it induces a dramatic increase in the
CC tail bleeding time, and has a strong antithrombotic activity
CC (PubMed:18508682). On ITGAV/ITGB3, it inhibits the adhesion of
CC ITGAV/ITGB3-expressing human microvascular endothelial cell line and
CC murine melanoma cell line to vitronectin (IC(50) = 555 nM and 225 nM,
CC respectively), and transiently inhibits their proliferation without
CC direct cell toxicity. In vivo, it potently inhibits angiogenesis and
CC metastasis (PubMed:17952617), probably due to its capability to
CC strongly inhibit the expression of VEGF and its receptors in
CC endothelial cells (PubMed:22561350). It also inhibits tumor cell
CC migration in vitro (PubMed:22069567). {ECO:0000269|PubMed:17952617,
CC ECO:0000269|PubMed:18508682, ECO:0000269|PubMed:22069567,
CC ECO:0000269|PubMed:22561350}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MISCELLANEOUS: Is derived from the P-II subfamily of the venom
CC metalloproteinase (M12B) family.
CC -!- MISCELLANEOUS: The interaction between the disintegrin and the integrin
CC ITGAV/ITGB3 is inhibited by EDTA, indicating a cation sensitive
CC binding. {ECO:0000305|PubMed:17952617}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the medium disintegrin
CC subfamily.
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; AY259516; AAO75107.1; -; mRNA.
DR AlphaFoldDB; Q801Z4; -.
DR SMR; Q801Z4; -.
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 Cell adhesion impairing toxin; Disulfide bond; Hemostasis impairing toxin;
KW Platelet aggregation inhibiting toxin; Secreted; Toxin.
FT CHAIN 1..78
FT /note="Disintegrin DisBa-01"
FT /id="PRO_0000424615"
FT DOMAIN 1..78
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 56..58
FT /note="Cell attachment site"
FT SITE 53
FT /note="May bind to alpha-V integrin (ITGAV) subunit"
FT SITE 56
FT /note="May bind to alpha-V integrin (ITGAV) subunit"
FT SITE 58
FT /note="May bind to metal ioncoordinated at the beta-3
FT integrin (ITGB3) subunit"
FT SITE 73
FT /note="May bind to alpha-V integrin (ITGAV) subunit"
FT SITE 76
FT /note="May bind to beta-3 integrin (ITGB3) subunit"
FT SITE 77
FT /note="May bind to both beta-3 (ITGB3) and alpha-V (ITGAV)
FT integrin subunits"
FT DISULFID 11..20
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 13..21
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 26..40
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 34..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 39..43
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 52..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
SQ SEQUENCE 78 AA; 8236 MW; 1BAA8D926E29180D CRC64;
GNELLEAGEE CDCGTPGNPC CDAATCKLRP GAQCAEGLCC DQCRFMKEGT VCRIARGDDM
DDYCNGISAG CPRNPFHA
