ID   TICK1_RHIAP             Reviewed;          98 AA.
AC   C5H8E7;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 1.
DT   25-MAY-2022, entry version 26.
DE   RecName: Full=R.appendiculatus Kunitz/BPTI-like protein {ECO:0000303|PubMed:19394347};
DE            Short=Ra-KLP {ECO:0000303|PubMed:19394347};
DE   AltName: Full=Kunitz/BPTI-like protein {ECO:0000312|EMBL:ACM86785.1};
DE   AltName: Full=Pancreatic trypsin inhibitor {ECO:0000312|EMBL:JAP78109.1};
DE   Flags: Precursor;
OS   Rhipicephalus appendiculatus (Brown ear tick).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC   Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Rhipicephalinae;
OC   Rhipicephalus; Rhipicephalus.
OX   NCBI_TaxID=34631;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], RECOMBINANT EXPRESSION, X-RAY CRYSTALLOGRAPHY
RP   (1.6 ANGSTROMS) OF 34-98, DISULFIDE BONDS, SUBUNIT, AND DEVELOPMENTAL
RP   STAGE.
RC   TISSUE=Salivary gland;
RX   PubMed=19394347; DOI=10.1016/j.jmb.2009.04.045;
RA   Paesen G.C., Siebold C., Dallas M.L., Peers C., Harlos K., Nuttall P.A.,
RA   Nunn M.A., Stuart D.I., Esnouf R.M.;
RT   "An ion-channel modulator from the saliva of the brown ear tick has a
RT   highly modified Kunitz/BPTI structure.";
RL   J. Mol. Biol. 389:734-747(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Salivary gland;
RX   PubMed=26830274; DOI=10.1016/j.ttbdis.2016.01.014;
RA   de Castro M.H., de Klerk D., Pienaar R., Latif A.A., Rees D.J., Mans B.J.;
RT   "De novo assembly and annotation of the salivary gland transcriptome of
RT   Rhipicephalus appendiculatus male and female ticks during blood feeding.";
RL   Ticks Tick Borne Dis. 7:536-548(2016).
CC   -!- FUNCTION: Activates large conductance calcium-activated potassium
CC       channels (maxiK, KCNMA1/KCNMB), when tested at micromolar
CC       concentrations, suggesting a potential mechanism for regulating host
CC       blood supply during feeding (PubMed:19394347). Shows no antiprotease
CC       activity, and does not prevent ADP-, PAF- or collagen-induced platelet
CC       aggregation (PubMed:19394347). Has no effect on blood coagulation and
CC       does not inhibit the alternative or classical complement cascades
CC       (PubMed:19394347). {ECO:0000269|PubMed:19394347}.
CC   -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:19394347}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:19394347}.
CC   -!- TISSUE SPECIFICITY: Expressed by the salivary glands.
CC       {ECO:0000305|PubMed:19394347}.
CC   -!- DEVELOPMENTAL STAGE: Only detected in the salivary glands of adult
CC       female ticks between 2 to 4 days after attachment to the host animal.
CC       Is not obtained from nymphs, larvae or adult male ticks. Is only
CC       detected in a quarter of pairs of glands, suggesting non-continuous
CC       production of the protein or slow repletion of stocks following
CC       salivation. {ECO:0000269|PubMed:19394347}.
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DR   EMBL; FJ042889; ACM86785.1; -; mRNA.
DR   EMBL; GEDV01010448; JAP78109.1; -; Transcribed_RNA.
DR   PDB; 2W8X; X-ray; 1.60 A; A/B=34-98.
DR   PDBsum; 2W8X; -.
DR   AlphaFoldDB; C5H8E7; -.
DR   SMR; C5H8E7; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; 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   3D-structure; Calcium-activated potassium channel impairing toxin;
KW   Disulfide bond; Ion channel impairing toxin;
KW   Potassium channel impairing toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..98
FT                   /note="R.appendiculatus Kunitz/BPTI-like protein"
FT                   /id="PRO_5008758406"
FT   DISULFID        36..51
FT                   /evidence="ECO:0000269|PubMed:19394347,
FT                   ECO:0007744|PDB:2W8X"
FT   DISULFID        43..83
FT                   /evidence="ECO:0000269|PubMed:19394347,
FT                   ECO:0007744|PDB:2W8X"
FT   DISULFID        49..96
FT                   /evidence="ECO:0000269|PubMed:19394347,
FT                   ECO:0007744|PDB:2W8X"
FT   DISULFID        74..92
FT                   /evidence="ECO:0000269|PubMed:19394347,
FT                   ECO:0007744|PDB:2W8X"
SQ   SEQUENCE   98 AA;  11111 MW;  129EFCDC7F6D55ED CRC64;
     MASTLKLFML LPVILLLLQE AYGTIDVEAR GDNFNCNKRE GPCSQRSLCE CDPNLQLGRH
     SDQLWHYNLR TNRCERGGYR DNCNSHTSSG ACVMACER