ID   KUNI_ORNKA              Reviewed;         134 AA.
AC   Q8WPG5;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   03-AUG-2022, entry version 46.
DE   RecName: Full=Thrombin inhibitor savignin {ECO:0000303|PubMed:10502470, ECO:0000303|PubMed:12044499};
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:AAL37210.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], 3D-STRUCTURE MODELING, AND FUNCTION.
RC   TISSUE=Salivary gland;
RX   PubMed=12044499; DOI=10.1016/s0965-1748(01)00169-2;
RA   Mans B.J., Louw A.I., Neitz A.W.;
RT   "Amino acid sequence and structure modeling of savignin, a thrombin
RT   inhibitor from the tick, Ornithodoros savignyi.";
RL   Insect Biochem. Mol. Biol. 32:821-828(2002).
RN   [2]
RP   PROTEIN SEQUENCE OF 17-27, FUNCTION, AND MASS SPECTROMETRY.
RC   TISSUE=Salivary gland;
RX   PubMed=10502470; DOI=10.1006/expr.1999.4448;
RA   Nienaber J., Gaspar A.R., Neitz A.W.;
RT   "Savignin, a potent thrombin inhibitor isolated from the salivary glands of
RT   the tick Ornithodoros savignyi (Acari: Argasidae).";
RL   Exp. Parasitol. 93:82-91(1999).
CC   -!- FUNCTION: Tick salivary thrombin inhibitor that plays an important part
CC       in the anti-hemostatic strategy of ticks. Inhibits thrombin-induced
CC       platelet aggregation, but has no effect on ADP- or collagen-induced
CC       aggregation (PubMed:10502470). Is a competitive, slow-, tight-binding
CC       inhibitor of thrombin (Ki=4.89 pM) (PubMed:10502470). It requires
CC       thrombin fibrinogen-binding exosite for optimal inhibition, as its
CC       affinity for thrombin lacking the exosite is much lower (Ki=22.3 nM)
CC       (PubMed:10502470). Its N-terminal amino acid residues may bind inside
CC       the active site cleft of thrombin, while its C-terminal domain may
CC       interact with the basic fibrinogen recognition exosite of thrombin
CC       (PubMed:12044499). It does not inhibit plasmin, factor Xa (F10), and
CC       trypsin (PubMed:10502470). {ECO:0000269|PubMed:10502470,
CC       ECO:0000269|PubMed:12044499}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC       {ECO:0000250|UniProtKB:Q8MVZ2}. Secreted {ECO:0000305|PubMed:10502470}.
CC   -!- TISSUE SPECIFICITY: Expressed in salivary glands.
CC       {ECO:0000305|PubMed:10502470}.
CC   -!- MASS SPECTROMETRY: Mass=12430.4; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:10502470};
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DR   EMBL; AF321524; AAL37210.1; -; mRNA.
DR   MEROPS; I02.035; -.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   Gene3D; 4.10.410.10; -; 2.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   SUPFAM; SSF57362; SSF57362; 2.
PE   1: Evidence at protein level;
KW   Blood coagulation cascade inhibiting toxin; Cytoplasmic vesicle;
KW   Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW   Platelet aggregation inhibiting toxin; Repeat; Secreted; Signal; Toxin.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..134
FT                   /note="Thrombin inhibitor savignin"
FT                   /evidence="ECO:0000305|PubMed:10502470,
FT                   ECO:0000305|PubMed:12044499"
FT                   /id="PRO_5004315397"
FT   DOMAIN          17..69
FT                   /note="BPTI/Kunitz inhibitor 1"
FT                   /evidence="ECO:0000250|UniProtKB:P56409,
FT                   ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DOMAIN          83..129
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   REGION          70..82
FT                   /note="Linker"
FT                   /evidence="ECO:0000305"
FT   DISULFID        21..66
FT                   /evidence="ECO:0000250|UniProtKB:P56409"
FT   DISULFID        29..51
FT                   /evidence="ECO:0000250|UniProtKB:P56409"
FT   DISULFID        45..62
FT                   /evidence="ECO:0000250|UniProtKB:P56409"
FT   DISULFID        81..129
FT                   /evidence="ECO:0000250|UniProtKB:P56409"
FT   DISULFID        89..112
FT                   /evidence="ECO:0000250|UniProtKB:P56409"
FT   DISULFID        105..125
FT                   /evidence="ECO:0000250|UniProtKB:P56409"
SQ   SEQUENCE   134 AA;  14100 MW;  7D66220BF6BBB608 CRC64;
     MLFYVVITLV AGTVSGLNVR CNNPHTANCE NGAKLESYFR EGETCVGSPA CPGEGYATKE
     DCQKACFPGG GDHSTNVDSS CFGQPPTSCE TGAEVTYYDS GSRTCKVLQH GCPSSENAFD
     SEIECQVACG VSME