ID   KUNPG_ORNMO             Reviewed;          60 AA.
AC   P36235;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   03-AUG-2022, entry version 60.
DE   RecName: Full=Disagregin {ECO:0000303|PubMed:8120028};
DE   AltName: Full=Antihemostatic agent {ECO:0000303|PubMed:33537548};
DE   AltName: Full=Platelet aggregation inhibitor {ECO:0000303|PubMed:8120028};
DE            Short=PAI {ECO:0000250|UniProtKB:Q8MVZ2};
OS   Ornithodoros moubata (Soft tick) (Argasid tick).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC   Parasitiformes; Ixodida; Ixodoidea; Argasidae; Ornithodoros.
OX   NCBI_TaxID=6938;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Salivary gland;
RX   PubMed=8120028; DOI=10.1016/s0021-9258(17)37432-x;
RA   Karczewski J., Endris R., Connolly T.M.;
RT   "Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp
RT   sequence from the tick, Ornithodoros moubata.";
RL   J. Biol. Chem. 269:6702-6708(1994).
RN   [2]
RP   FUNCTION.
RX   PubMed=9434779; DOI=10.1006/bbrc.1997.7881;
RA   Karczewski J., Connolly T.M.;
RT   "The interaction of disagregin with the platelet fibrinogen receptor,
RT   glycoprotein IIb-IIIa.";
RL   Biochem. Biophys. Res. Commun. 241:744-748(1997).
RN   [3]
RP   FUNCTION, SYNTHESIS, 3D-STRUCTURE MODELING IN COMPLEX WITH ITGA2B/ITGB3,
RP   AND MUTAGENESIS OF GLU-15.
RX   PubMed=33537548; DOI=10.1002/rth2.12466;
RA   van den Kerkhof D.L., Nagy M., Wichapong K., Brouns S.L.N.,
RA   Heemskerk J.W.M., Hackeng T.M., Dijkgraaf I.;
RT   "Inhibition of platelet adhesion, thrombus formation, and fibrin formation
RT   by a potent alphaIIbbeta3 integrin inhibitor from ticks.";
RL   Res. Pract. Thromb. Haemost. 5:231-242(2021).
CC   -!- FUNCTION: Tick salivary platelet aggregation inhibitor that plays an
CC       important part in the anti-hemostatic strategy of ticks
CC       (PubMed:8120028). Inhibits fibrinogen interaction with platelets
CC       (PubMed:8120028). Acts by binding (in a divalent metal ion dependent
CC       manner) to the glycoprotein IIb-IIIa receptor (ITGA2B/ITGB3) on the
CC       platelet surface and inhibits aggregation induced by ADP (IC(50)=99-104
CC       nM), thrombin, collagen (IC(50)=64 nM) platelet-activating factor and
CC       collagen (PubMed:8120028, PubMed:9434779, PubMed:33537548). Interacts
CC       to unstimulated platelets (Kd=42.5 nM) and to ADP-stimulated platelets
CC       (Kd=39.4 nM) (PubMed:8120028). In contrast to many disintegrins which
CC       only interact with the beta-3 subunit, interacts with the two subunits
CC       (alpha-IIb and beta-3) (PubMed:8120028, PubMed:9434779). Under flow
CC       conditions, reduces and delays platelet adhesion, aggregation, and
CC       fibrin formation (PubMed:33537548). {ECO:0000269|PubMed:33537548,
CC       ECO:0000269|PubMed:8120028, ECO:0000269|PubMed:9434779}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8120028}.
CC   -!- TISSUE SPECIFICITY: Expressed in salivary glands.
CC       {ECO:0000305|PubMed:8120028}.
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DR   PIR; A54369; A54369.
DR   AlphaFoldDB; P36235; -.
DR   SMR; P36235; -.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
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; Direct protein sequencing;
KW   Hemostasis impairing toxin; Platelet aggregation inhibiting toxin;
KW   Secreted; Toxin.
FT   CHAIN           1..60
FT                   /note="Disagregin"
FT                   /evidence="ECO:0000269|PubMed:8120028"
FT                   /id="PRO_0000079919"
FT   MOTIF           14..16
FT                   /note="Cell attachment site; atypical"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         15
FT                   /note="E->G: RGD-disagregin; no change in ability to
FT                   inhibit platelet aggregation induced by ADP or collagen,
FT                   and under flow conditions, no change in abrogating platelet
FT                   adhesion, aggregation, and fibrin formation."
FT                   /evidence="ECO:0000269|PubMed:33537548"
SQ   SEQUENCE   60 AA;  6962 MW;  EB102D1F7FA56F98 CRC64;
     SDDKCQGRPM YGCREDDDSV FGWTYDSNHG QCWKGSYCKH RRQPSNYFAS QQECRNTCGA