ID   KUN_HAELO               Reviewed;         141 AA.
AC   B6ZIW0;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 1.
DT   03-AUG-2022, entry version 38.
DE   RecName: Full=Thrombin inhibitor hemalin {ECO:0000303|PubMed:19061894};
DE   AltName: Full=Thrombin inhibitor haemalin {ECO:0000312|EMBL:BAH02683.1};
DE   Flags: Precursor;
OS   Haemaphysalis longicornis (Bush tick).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC   Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Haemaphysalinae;
OC   Haemaphysalis.
OX   NCBI_TaxID=44386;
RN   [1] {ECO:0000312|EMBL:BAH02683.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND RECOMBINANT
RP   EXPRESSION.
RC   STRAIN=Okayama; TISSUE=Midgut;
RX   PubMed=19061894; DOI=10.1016/j.jinsphys.2008.11.004;
RA   Liao M., Zhou J., Gong H., Boldbaatar D., Shirafuji R., Battur B.,
RA   Nishikawa Y., Fujisaki K.;
RT   "Hemalin, a thrombin inhibitor isolated from a midgut cDNA library from the
RT   hard tick Haemaphysalis longicornis.";
RL   J. Insect Physiol. 55:164-173(2009).
CC   -!- FUNCTION: Anticoagulant protein that may inhibit thrombin by binding to
CC       its exosite I. Also inhibits the amidolytic activity of trypsin (tested
CC       on the substrate S-2238). The recombinant protein delays plasma
CC       clotting time and inhibits both thrombin-induced fibrinogen clotting
CC       and thrombin-induced platelet aggregation in a dose-dependent manner.
CC       May be an anticoagulant for the common pathway of blood coagulation.
CC       {ECO:0000269|PubMed:19061894}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19061894}.
CC   -!- TISSUE SPECIFICITY: Expressed in the major tissues of the adult female
CC       tick, including the midgut (highest expression), salivary glands,
CC       ovaries, hemolymph, and fat bodies. {ECO:0000269|PubMed:19061894}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at larval, nymphal, and adult stages of
CC       fed and unfed ticks, but not expressed at the egg stage. Has the
CC       highest expression in the rapid blood meal sucking period (3-4 days
CC       after feeding) of all the stages. {ECO:0000269|PubMed:19061894}.
CC   -!- DISRUPTION PHENOTYPE: After gene silencing by RNA interference, the
CC       tick attachment time is prolonged and about 25% of RNA-treated ticks do
CC       not successfully complete the blood feeding and detach from the host.
CC       No significant difference is observed in the engorgement body, egg
CC       weight, and hatching capability of eggs. {ECO:0000269|PubMed:19061894}.
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DR   EMBL; AB440203; BAH02683.1; -; mRNA.
DR   MEROPS; I02.057; -.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0044562; P:envenomation resulting in negative regulation of voltage-gated potassium channel activity in another organism; IEA:UniProt.
DR   CDD; cd00109; KU; 2.
DR   Gene3D; 4.10.410.10; -; 2.
DR   InterPro; IPR002223; Kunitz_BPTI.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR   Pfam; PF00014; Kunitz_BPTI; 2.
DR   PRINTS; PR00759; BASICPTASE.
DR   SMART; SM00131; KU; 2.
DR   SUPFAM; SSF57362; SSF57362; 2.
DR   PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 2.
PE   2: Evidence at transcript level;
KW   Blood coagulation cascade inhibiting toxin; Cell adhesion impairing toxin;
KW   Disulfide bond; Hemostasis impairing toxin;
KW   Platelet aggregation inhibiting toxin; Protease inhibitor; Repeat;
KW   Secreted; Serine protease inhibitor; Signal; Toxin.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000255"
FT   CHAIN           16..141
FT                   /note="Thrombin inhibitor hemalin"
FT                   /id="PRO_5013197916"
FT   DOMAIN          21..71
FT                   /note="BPTI/Kunitz inhibitor 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DOMAIN          89..139
FT                   /note="BPTI/Kunitz inhibitor 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        21..71
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        30..54
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        46..67
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        89..139
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        98..122
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        114..135
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
SQ   SEQUENCE   141 AA;  15886 MW;  6390769873538B4A CRC64;
     MKLFVFLALF GAAFAQRNGF CRLPAEPGIC RAFMPRYYFD VEKGQCEQFI YGGCKGNENN
     FETLKECQDA CGEPERASDF EKADFETGCK AAPETGLCKA SFERWFFNAA SGECEEFIYG
     GCGGNDNNYE NKEECEFACK Y