ID   VM2JA_BOTJA             Reviewed;          88 AA.
AC   Q0NZX5;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   19-SEP-2006, sequence version 1.
DT   25-MAY-2022, entry version 60.
DE   RecName: Full=Disintegrin jarastatin;
DE            Short=JT;
DE   AltName: Full=Platelet aggregation activation inhibitor;
DE   Contains:
DE     RecName: Full=Disintegrin jarastatin;
DE   Contains:
DE     RecName: Full=Disintegrin jarastatin-AGEEC;
DE   Contains:
DE     RecName: Full=Disintegrin jarastatin-GEEC;
DE   Contains:
DE     RecName: Full=Disintegrin jarastatin-EC;
DE   Flags: Precursor; Fragment;
OS   Bothrops jararaca (Jararaca) (Bothrops jajaraca).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX   NCBI_TaxID=8724;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=16919699; DOI=10.1016/j.toxicon.2006.07.010;
RA   Cidade D.A.P., Wermelinger L.S., Lobo-Hajdu G., Davila A.M.R., Bon C.,
RA   Zingali R.B., Albano R.M.;
RT   "Molecular diversity of disintegrin-like domains within metalloproteinase
RT   precursors of Bothrops jararaca.";
RL   Toxicon 48:590-599(2006).
RN   [2]
RP   PROTEIN SEQUENCE OF 16-84, AND FUNCTION.
RX   PubMed=10471323; DOI=10.1006/excr.1999.4583;
RA   Coelho A.L.J., de Freitas M.S., Oliveira-Carvalho A.L., Moura-Neto V.,
RA   Zingali R.B., Barja-Fidalgo C.;
RT   "Effects of jarastatin, a novel snake venom disintegrin, on neutrophil
RT   migration and actin cytoskeleton dynamics.";
RL   Exp. Cell Res. 251:379-387(1999).
RN   [3]
RP   FUNCTION.
RX   PubMed=14697344; DOI=10.1016/j.yexcr.2003.09.013;
RA   Coelho A.L.J., De Freitas M.S., Mariano-Oliveira A., Rapozo D.C.M.,
RA   Pinto L.F.R., Niewiarowski S., Zingali R.B., Marcinkiewicz C.,
RA   Barja-Fidalgo C.;
RT   "RGD- and MLD-disintegrins, jarastatin and EC3, activate integrin-mediated
RT   signaling modulating the human neutrophils chemotaxis, apoptosis and IL-8
RT   gene expression.";
RL   Exp. Cell Res. 292:371-384(2004).
RN   [4]
RP   FUNCTION ON MELANOMA CELLS.
RX   PubMed=17854854; DOI=10.1016/j.toxicon.2007.07.016;
RA   Oliva I.B., Coelho R.M., Barcellos G.G., Saldanha-Gama R.,
RA   Wermelinger L.S., Marcinkiewicz C., Zingali R.B., Barja-Fidalgo C.;
RT   "Effect of RGD-disintegrins on melanoma cell growth and metastasis:
RT   involvement of the actin cytoskeleton, FAK and c-Fos.";
RL   Toxicon 50:1053-1063(2007).
CC   -!- FUNCTION: Binds alpha-5/beta-1 (ITGAV/ITGB1), alpha-V/beta-3
CC       (ITGAV/ITGB3) and alpha-M/beta-2 (ITGAM/ITGB2) integrins. Is a potent
CC       inhibitor of platelet aggregation induced by ADP, collagen, and
CC       thrombin. Induces neutrophil chemotaxis and inhibits the chemotaxis of
CC       human neutrophils toward fMLP, IL-8, and jarastatin itself. Directly
CC       activates an integrin-coupled signaling and modulate the MAPK pathway
CC       in different ways, leading the neutrophils to express different
CC       functional response. Jarastatin-treated neutrophils accumulates F-actin
CC       at the plasmalemma. Induces PTK2/FAK1 and phosphoinositide 3-kinase
CC       (PI3K) activation. Induces Erk-2 translocation to nucleus and a delay
CC       of the spontaneous apoptosis of neutrophils. Increases the IL-8 mRNA
CC       levels in neutrophils. When injected simultaneously with melanoma cells
CC       in mice, jarastatin, flavoridin (FL) and kistrin (KR), significantly
CC       reduce tumor lung colonization. Jarastatin inhibits B16F10 cell growth
CC       in vitro. When it interacts with melanoma cells, it induces actin
CC       cytoskeleton rearrangement, increasing actin polymerization and
CC       PTK2/FAK1 phosphorylation. Interferes with NF-kappaB translocation in
CC       melanoma cells. {ECO:0000269|PubMed:10471323,
CC       ECO:0000269|PubMed:14697344, ECO:0000269|PubMed:17854854}.
CC   -!- SUBUNIT: Monomer.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- MASS SPECTROMETRY: [Disintegrin jarastatin]: Mass=7753.89;
CC       Method=MALDI; Evidence={ECO:0000269|PubMed:16919699};
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; DQ375441; ABD34834.1; -; mRNA.
DR   AlphaFoldDB; Q0NZX5; -.
DR   SMR; Q0NZX5; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0006935; P:chemotaxis; 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   Apoptosis; Cell adhesion impairing toxin; Chemotaxis;
KW   Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW   Platelet aggregation inhibiting toxin; Secreted; Toxin.
FT   PROPEP          <1..15
FT                   /evidence="ECO:0000269|PubMed:10471323"
FT                   /id="PRO_0000340281"
FT   CHAIN           16..88
FT                   /note="Disintegrin jarastatin"
FT                   /id="PRO_0000340282"
FT   CHAIN           17..88
FT                   /note="Disintegrin jarastatin-AGEEC"
FT                   /id="PRO_0000340283"
FT   CHAIN           18..88
FT                   /note="Disintegrin jarastatin-GEEC"
FT                   /id="PRO_0000340284"
FT   CHAIN           20..88
FT                   /note="Disintegrin jarastatin-EC"
FT                   /id="PRO_0000340285"
FT   DOMAIN          7..88
FT                   /note="Disintegrin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   MOTIF           66..68
FT                   /note="Cell attachment site"
FT   DISULFID        21..30
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DISULFID        23..31
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DISULFID        36..50
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DISULFID        44..74
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DISULFID        49..53
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DISULFID        62..81
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   CONFLICT        27
FT                   /note="G -> E (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   NON_TER         1
SQ   SEQUENCE   88 AA;  9323 MW;  906F0B51A408D280 CRC64;
     RTDTVSTPVS GNELLEAGEE CDCGTPGNPC CDAATCKLRP GAQCAEGLCC DQCRFMKEGT
     VCRRARGDDM DDYCNGISAG CPRNPFHA