ID   CM3K_CONRA              Reviewed;          75 AA.
AC   P69769;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   11-JUL-2006, sequence version 2.
DT   25-MAY-2022, entry version 44.
DE   RecName: Full=Kappa-conotoxin RIIIK;
DE            Short=Kappa-M-RIIIK;
DE   AltName: Full=Conotoxin R3.1;
DE   Flags: Precursor;
OS   Conus radiatus (Rayed cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Phasmoconus.
OX   NCBI_TaxID=61198;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=15924437; DOI=10.1021/bi047541b;
RA   Corpuz G.P., Jacobsen R.B., Jimenez E.C., Watkins M., Walker C.,
RA   Colledge C., Garrett J.E., McDougal O., Li W., Gray W.R., Hillyard D.R.,
RA   Rivier J., McIntosh J.M., Cruz L.J., Olivera B.M.;
RT   "Definition of the M-conotoxin superfamily: characterization of novel
RT   peptides from molluscivorous Conus venoms.";
RL   Biochemistry 44:8176-8186(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 48-75, SYNTHESIS OF 51-74, FUNCTION, AND
RP   TOXIN TARGET.
RC   TISSUE=Venom duct;
RX   PubMed=12399472; DOI=10.1074/jbc.m205953200;
RA   Ferber M., Sporning A., Jeserich G., DeLaCruz R., Watkins M., Olivera B.M.,
RA   Terlau H.;
RT   "A novel conus peptide ligand for K+ channels.";
RL   J. Biol. Chem. 278:2177-2183(2003).
RN   [3]
RP   FUNCTION, TOXIN TARGET, ASSAY ON RAT ISCHEMIA/REPERFUSION MODEL, AND
RP   MUTAGENESIS OF LEU-59.
RC   TISSUE=Venom;
RX   PubMed=20220134; DOI=10.1074/jbc.m109.068486;
RA   Chen P., Dendorfer A., Finol-Urdaneta R.K., Terlau H., Olivera B.M.;
RT   "Biochemical characterization of kappaM-RIIIJ, a Kv1.2 channel blocker:
RT   evaluation of cardioprotective effects of kappaM-conotoxins.";
RL   J. Biol. Chem. 285:14882-14889(2010).
CC   -!- FUNCTION: Kappa-conotoxins inhibits voltage-gated potassium channels
CC       (Kv). This synthetic toxin reversibly inhibits the insect potassium
CC       channel Shaker K+, the teleost homolog TSha1 and the mammalian
CC       Kv1.2/KCNA2 channel. Interacts with the pore region of the insect
CC       channel, in a state-dependent manner. Causes seizure when
CC       intracerebrovascularly injected into mice. Is also toxic when
CC       intrathecally injected into mice, but shows no visible effects by
CC       intraperitoneal injection. Shows protective effects on cardiac tissue
CC       when administered after an ischemic event.
CC       {ECO:0000269|PubMed:12399472, ECO:0000269|PubMed:20220134}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC   -!- DOMAIN: The cysteine framework is III (CC-C-C-CC). Classified in the M-
CC       4 branch, since 4 residues stand between the fourth and the fifth
CC       cysteine residues.
CC   -!- MISCELLANEOUS: Has no or very low potency on Kv1.1/KCNA1, Kv1.3/KCNA3,
CC       Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6, Kv2.1/KCNB1, Kv3.4/KCNC4,
CC       Kv4.2/KCND2, Kv7.2/KCNQ2-Kv7.3/KCNQ3, Kv10.1/KCNH1, Kv11.1/KCNH2, and
CC       KCa1.1/KCNMA1. Has no effect on sodium channels (Nav1.2/SCN2A,
CC       Nav1.4/SCN4A, and Nav1.5/SCN5A) (PubMed:12399472).
CC       {ECO:0000305|PubMed:12399472}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P69769; -.
DR   ConoServer; 1521; RIIIK precursor.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR004214; Conotoxin.
DR   Pfam; PF02950; Conotoxin; 1.
PE   2: Evidence at transcript level;
KW   Amidation; Cleavage on pair of basic residues; Disulfide bond;
KW   Hydroxylation; Ion channel impairing toxin; Neurotoxin;
KW   Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW   Voltage-gated potassium channel impairing toxin.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..50
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000035051"
FT   PEPTIDE         51..74
FT                   /note="Kappa-conotoxin RIIIK"
FT                   /id="PRO_0000035052"
FT   MOD_RES         52
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         63
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         65
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         71
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         74
FT                   /note="Threonine amide"
FT                   /evidence="ECO:0000250"
FT   DISULFID        54..67
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        55..72
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        62..73
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   MUTAGEN         59
FT                   /note="L->K: 3.5-fold increase of potency for Kv1.2/KCNA2."
FT                   /evidence="ECO:0000269|PubMed:20220134"
SQ   SEQUENCE   75 AA;  8351 MW;  D152B7490276196F CRC64;
     MSKLGVLLTI CLLLFPLTAL PMDGDQPVDR LAERMQDNIS SEQHTFFEKR LPSCCSLNLR
     LCPVPACKRN PCCTG