ID   KUNPP_ORNKA             Reviewed;          82 AA.
AC   Q8MVZ3;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   03-AUG-2022, entry version 38.
DE   RecName: Full=Savignygrin (+) {ECO:0000303|PubMed:11932256, ECO:0000303|PubMed:12593588};
DE   AltName: Full=Platelet aggregation inhibitor {ECO:0000303|PubMed:11932256};
DE            Short=PAI {ECO:0000303|PubMed:11932256};
DE   Flags: Precursor;
OS   Ornithodoros kalahariensis (Tick).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC   Parasitiformes; Ixodida; Ixodoidea; Argasidae; Ornithodoros.
OX   NCBI_TaxID=1580572;
RN   [1] {ECO:0000312|EMBL:AAM54047.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-42, FUNCTION, MASS
RP   SPECTROMETRY, AND 3D-STRUCTURE MODELING.
RC   TISSUE=Salivary gland;
RX   PubMed=11932256; DOI=10.1074/jbc.m112060200;
RA   Mans B.J., Louw A.I., Neitz A.W.;
RT   "Savignygrin, a platelet aggregation inhibitor from the soft tick
RT   Ornithodoros savignyi, presents the RGD integrin recognition motif on the
RT   Kunitz-BPTI fold.";
RL   J. Biol. Chem. 277:21371-21378(2002).
RN   [2]
RP   FUNCTION.
RX   PubMed=12593588; DOI=10.1023/a:1021613001297;
RA   Mans B.J., Louw A.I., Neitz A.W.;
RT   "Disaggregation of aggregated platelets by savignygrin, a alphaIIbeta3
RT   antagonist from Ornithodoros savignyi.";
RL   Exp. Appl. Acarol. 27:231-239(2002).
RN   [3]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Salivary gland;
RX   PubMed=15285144; DOI=10.1023/b:appa.0000030012.47964.b3;
RA   Mans B.J., Venter J.D., Coons L.B., Louw A.I., Neitz A.W.;
RT   "A reassessment of argasid tick salivary gland ultrastructure from an
RT   immuno-cytochemical perspective.";
RL   Exp. Appl. Acarol. 33:119-129(2004).
RN   [4]
RP   FUNCTION, AND 3D-STRUCTURE MODELING IN COMPLEX WITH INTEGRIN ITGA2B/ITGB3.
RC   TISSUE=Salivary gland;
RX   PubMed=15147758; DOI=10.1016/j.ibmb.2004.03.005;
RA   Mans B.J., Neitz A.W.;
RT   "The mechanism of alphaIIbbeta3 antagonism by savignygrin and its
RT   implications for the evolution of anti-hemostatic strategies in soft
RT   ticks.";
RL   Insect Biochem. Mol. Biol. 34:573-584(2004).
CC   -!- FUNCTION: Tick salivary platelet aggregation inhibitor that plays an
CC       important part in the anti-hemostatic strategy of ticks
CC       (PubMed:11932256). Inhibits platelet aggregation induced by ADP
CC       (IC(50)=130 nM), collagen, the thrombin receptor-activating peptide,
CC       and epinephrine, although platelets are activated and their shape
CC       changed (PubMed:11932256). Binding to platelets is similar for resting
CC       and activated platelets (Kd=50-70 nM) (PubMed:15147758). Acts by
CC       specifically binding to platelet membrane glycoprotein IIb-IIIa
CC       (ITGA2B/ITGB3) in a divalent metal ion dependent manner (Probable)
CC       (PubMed:15147758). In contrast to many disintegrins which only
CC       interacts with the beta-3 subunit, this protein interacts with the two
CC       subunits (alpha-IIb and beta-3) (Probable). Also causes disaggregation
CC       of aggregated platelets without influencing the activated spherical
CC       shape associated with aggregated platelets and causes a decrease in the
CC       number of pseudopodia on the activated platelet surface
CC       (PubMed:12593588). Does not show any inhibitory activity for the
CC       different serine proteases tested (PubMed:11932256).
CC       {ECO:0000269|PubMed:11932256, ECO:0000269|PubMed:12593588,
CC       ECO:0000269|PubMed:15147758, ECO:0000305|PubMed:11932256,
CC       ECO:0000305|PubMed:12593588, ECO:0000305|PubMed:15147758}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC       {ECO:0000269|PubMed:15285144}. Secreted {ECO:0000305|PubMed:11932256,
CC       ECO:0000305|PubMed:15285144}. Note=Before secretion, is localized to
CC       dense core granule type 'a' and to granule type 'b', but not to
CC       granules 'c' or 'd'. {ECO:0000269|PubMed:15285144}.
CC   -!- TISSUE SPECIFICITY: Expressed in salivary glands.
CC       {ECO:0000269|PubMed:15285144}.
CC   -!- MASS SPECTROMETRY: Mass=6966.18; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:11932256};
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DR   EMBL; AF452885; AAM54047.1; -; mRNA.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   Gene3D; 4.10.410.10; -; 1.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   SUPFAM; SSF57362; SSF57362; 1.
PE   1: Evidence at protein level;
KW   Cell adhesion impairing toxin; Cytoplasmic vesicle;
KW   Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW   Platelet aggregation inhibiting toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000305|PubMed:11932256"
FT   CHAIN           22..82
FT                   /note="Savignygrin (+)"
FT                   /evidence="ECO:0000305|PubMed:11932256"
FT                   /id="PRO_0000456103"
FT   MOTIF           35..37
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000269|PubMed:11932256"
FT   DISULFID        26..79
FT                   /evidence="ECO:0000305|PubMed:11932256"
FT   DISULFID        34..59
FT                   /evidence="ECO:0000305|PubMed:11932256"
FT   DISULFID        53..75
FT                   /evidence="ECO:0000305|PubMed:11932256"
SQ   SEQUENCE   82 AA;  9199 MW;  0621D5767C73344D CRC64;
     MQANIFVFAF LLLSVAVAAY GYQPECLEPS LYGCRGDEDA TFGWTFDRED GGCRQGSYCT
     RFGQPKNYFR SERDCKKACG NA