ID   VKTS1_CONST             Reviewed;          86 AA.
AC   P0C1X2;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   19-SEP-2006, sequence version 1.
DT   25-MAY-2022, entry version 71.
DE   RecName: Full=Kunitz-type conkunitzin-S1;
DE            Short=Conk-S1;
DE   Flags: Precursor;
OS   Conus striatus (Striated cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX   NCBI_TaxID=6493;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=16542850; DOI=10.1016/j.pep.2006.01.019;
RA   Bayrhuber M., Graf R., Ferber M., Zweckstetter M., Imperial J.,
RA   Garrett J.E., Olivera B.M., Terlau H., Becker S.;
RT   "Production of recombinant conkunitzin-S1 in Escherichia coli.";
RL   Protein Expr. Purif. 47:640-644(2006).
RN   [2]
RP   PROTEIN SEQUENCE OF 27-86, DISULFIDE BONDS, AMIDATION AT THR-86, FUNCTION,
RP   AND STRUCTURE BY NMR OF 27-86.
RC   TISSUE=Venom;
RX   PubMed=15833744; DOI=10.1074/jbc.c500064200;
RA   Bayrhuber M., Vijayan V., Ferber M., Graf R., Korukottu J., Imperial J.,
RA   Garrett J.E., Olivera B.M., Terlau H., Zweckstetter M., Becker S.;
RT   "Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family.
RT   Structural and functional characterization.";
RL   J. Biol. Chem. 280:23766-23770(2005).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 27-86.
RX   PubMed=16929098; DOI=10.1107/s0907444906021123;
RA   Dy C.Y., Buczek P., Imperial J.S., Bulaj G., Horvath M.P.;
RT   "Structure of conkunitzin-S1, a neurotoxin and Kunitz-fold disulfide
RT   variant from cone snail.";
RL   Acta Crystallogr. D 62:980-990(2006).
CC   -!- FUNCTION: Blocks specifically voltage-activated potassium channels (Kv)
CC       of the Shaker family (IC(50)=1.33 nM). {ECO:0000269|PubMed:15833744}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC   -!- PTM: Contains 2 disulfide bonds instead of 3, as for all Kunitz domain
CC       proteins. A double Cys-mutant carrying an additional Cys bridge does
CC       not show difference in activity with the natural peptide. However,
CC       there are some differences in the kinetics of binding of both peptides
CC       to the channel (PubMed:15833744). {ECO:0000269|PubMed:15833744}.
CC   -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
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DR   PDB; 1Y62; X-ray; 2.45 A; A/B/C/D/E/F=27-86.
DR   PDB; 2CA7; NMR; -; A=27-86.
DR   PDB; 6Q61; X-ray; 1.30 A; A=27-86.
DR   PDB; 6Q6C; X-ray; 1.30 A; A/B=27-86.
DR   PDB; 6YHY; X-ray; 1.55 A; A/B=28-85.
DR   PDBsum; 1Y62; -.
DR   PDBsum; 2CA7; -.
DR   PDBsum; 6Q61; -.
DR   PDBsum; 6Q6C; -.
DR   PDBsum; 6YHY; -.
DR   AlphaFoldDB; P0C1X2; -.
DR   BMRB; P0C1X2; -.
DR   SMR; P0C1X2; -.
DR   EvolutionaryTrace; P0C1X2; -.
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:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   CDD; cd00109; KU; 1.
DR   Gene3D; 4.10.410.10; -; 1.
DR   InterPro; IPR002223; Kunitz_BPTI.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   Pfam; PF00014; Kunitz_BPTI; 1.
DR   PRINTS; PR00759; BASICPTASE.
DR   SMART; SM00131; KU; 1.
DR   SUPFAM; SSF57362; SSF57362; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW   Protease inhibitor; Secreted; Serine protease inhibitor; Signal; Toxin;
KW   Voltage-gated potassium channel impairing toxin.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000269|PubMed:15833744"
FT   CHAIN           27..86
FT                   /note="Kunitz-type conkunitzin-S1"
FT                   /evidence="ECO:0000269|PubMed:15833744"
FT                   /id="PRO_0000249805"
FT   DOMAIN          33..83
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   MOD_RES         86
FT                   /note="Threonine amide"
FT                   /evidence="ECO:0000269|PubMed:15833744"
FT   DISULFID        33..83
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT                   ECO:0000269|PubMed:15833744"
FT   DISULFID        58..79
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT                   ECO:0000269|PubMed:15833744"
FT   HELIX           31..34
FT                   /evidence="ECO:0007829|PDB:6Q61"
FT   STRAND          41..43
FT                   /evidence="ECO:0007829|PDB:6Q6C"
FT   STRAND          46..52
FT                   /evidence="ECO:0007829|PDB:6Q61"
FT   TURN            53..56
FT                   /evidence="ECO:0007829|PDB:6Q61"
FT   STRAND          57..63
FT                   /evidence="ECO:0007829|PDB:6Q61"
FT   STRAND          65..67
FT                   /evidence="ECO:0007829|PDB:6Q61"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:6Q61"
FT   HELIX           76..83
FT                   /evidence="ECO:0007829|PDB:6Q61"
SQ   SEQUENCE   86 AA;  9661 MW;  69BEDED1DFE63355 CRC64;
     MEGRRFAAVL ILTICMLAPG TGTLLPKDRP SLCDLPADSG SGTKAEKRIY YNSARKQCLR
     FDYTGQGGNE NNFRRTYDCQ RTCLYT