ID   CM3J_CONRA              Reviewed;          25 AA.
AC   P0CG45;
DT   13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT   13-JUL-2010, sequence version 1.
DT   25-MAY-2022, entry version 26.
DE   RecName: Full=Kappa-conotoxin RIIIJ;
DE            Short=Kappa-M-RIIIJ;
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   PROTEIN SEQUENCE, FUNCTION, TOXIN TARGET, ASSAY ON RAT ISCHEMIA/REPERFUSION
RP   MODEL, MUTAGENESIS OF 6-THR--HIS-11; 6-THR--PRO-8; 9-LYS--HIS-11 AND
RP   10-LYS-HIS-11, SITE, HYDROXYLATION AT PRO-2; PRO-3; PRO-7; PRO-8; PRO-13;
RP   PRO-15 AND PRO-21, AND MASS SPECTROMETRY.
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       This toxin dose-dependently and reversibly inhibits the Kv1.2/KCNA2
CC       channel in mammalia. Does not exert protective effect on cardiac tissue
CC       when administered after an ischemic event.
CC       {ECO:0000269|PubMed:20220134}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
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   -!- MASS SPECTROMETRY: Mass=2805.84; Method=Electrospray;
CC       Note=monoisotopic.; Evidence={ECO:0000269|PubMed:20220134};
CC   -!- MISCELLANEOUS: Has no or very low potency for Kv1.1/KCNA1, Kv1.3/KCNA3,
CC       Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6, Kv7.2/KCNQ2-Kv7.3/KCNQ3, and
CC       KCa1.1/KCNMA1. {ECO:0000305|PubMed:20220134}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P0CG45; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019870; F:potassium channel inhibitor activity; IDA:CACAO.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Hydroxylation;
KW   Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW   Secreted; Toxin; Voltage-gated potassium channel impairing toxin.
FT   PEPTIDE         1..25
FT                   /note="Kappa-conotoxin RIIIJ"
FT                   /id="PRO_0000395613"
FT   SITE            9
FT                   /note="Significant for high potency for Kv1.2/KCNA2"
FT   MOD_RES         2
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MOD_RES         3
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MOD_RES         7
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MOD_RES         8
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MOD_RES         13
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MOD_RES         15
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MOD_RES         21
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   DISULFID        4..17
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        5..22
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        12..23
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   MUTAGEN         6..11
FT                   /note="TPPKKH->SLNLRL: 11-fold decrease in potency for
FT                   Kv1.2/KCNA2."
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MUTAGEN         6..8
FT                   /note="TPP->SLN: 2-fold decrease in potency for
FT                   Kv1.2/KCNA2."
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MUTAGEN         9..11
FT                   /note="KKH->LRL: 10-fold decrease in potency for
FT                   Kv1.2/KCNA2."
FT                   /evidence="ECO:0000269|PubMed:20220134"
FT   MUTAGEN         10..11
FT                   /note="KH->RL: 1.5-fold decrease in potency for
FT                   Kv1.2/KCNA2."
FT                   /evidence="ECO:0000269|PubMed:20220134"
SQ   SEQUENCE   25 AA;  2701 MW;  DDE9E2F99524B5F3 CRC64;
     LPPCCTPPKK HCPAPACKYK PCCKS