ID I1BA_CONRA Reviewed; 46 AA. AC Q7Z094; DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 11-DEC-2019, entry version 74. DE RecName: Full=Iota-conotoxin RXIA; DE AltName: Full=R11.6; DE AltName: Full=r11a; OS Conus radiatus (Rayed cone). OC Eukaryota; Metazoa; Lophotrochozoa; Mollusca; Gastropoda; Caenogastropoda; OC Neogastropoda; Conoidea; Conidae; Conus; Phasmoconus. OX NCBI_TaxID=61198; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE, HYDROXYLATION AT PRO-2; RP PRO-11 AND PRO-29, AND MASS SPECTROMETRY. RC TISSUE=Venom, and Venom duct; RX PubMed=12694387; DOI=10.1046/j.1471-4159.2003.01685.x; RA Jimenez E.C., Shetty R.P., Lirazan M., Rivier J., Walker C., Abogadie F.C., RA Yoshikami D., Cruz L.J., Olivera B.M.; RT "Novel excitatory Conus peptides define a new conotoxin superfamily."; RL J. Neurochem. 85:610-621(2003). RN [2] RP SYNTHESIS, AND D-AMINO ACID AT PHE-44. RC TISSUE=Venom; RX PubMed=15561705; DOI=10.1074/jbc.m405835200; RA Buczek O., Yoshikami D., Bulaj G., Jimenez E.C., Olivera B.M.; RT "Post-translational amino acid isomerization: a functionally important D- RT amino acid in an excitatory peptide."; RL J. Biol. Chem. 280:4247-4253(2005). RN [3] RP FUNCTION. RX PubMed=18486102; DOI=10.1016/j.bcp.2008.03.019; RA Fiedler B., Zhang M.M., Buczek O., Azam L., Bulaj G., Norton R.S., RA Olivera B.M., Yoshikami D.; RT "Specificity, affinity and efficacy of iota-conotoxin RXIA, an agonist of RT voltage-gated sodium channels Na(V)1.2, 1.6 and 1.7."; RL Biochem. Pharmacol. 75:2334-2344(2008). RN [4] RP STRUCTURE BY NMR, DISULFIDE BONDS, FUNCTION, AND SYNTHESIS (D-PHE AND RP L-PHE). RX PubMed=17696362; DOI=10.1021/bi700797f; RA Buczek O., Wei D., Babon J.J., Yang X., Fiedler B., Chen P., Yoshikami D., RA Olivera B.M., Bulaj G., Norton R.S.; RT "Structure and sodium channel activity of an excitatory I(1)-superfamily RT conotoxin."; RL Biochemistry 46:9929-9940(2007). RN [5] RP ERRATUM. RA Buczek O., Wei D., Babon J.J., Yang X., Fiedler B., Chen P., Yoshikami D., RA Olivera B.M., Bulaj G., Norton R.S.; RL Biochemistry 46:12887-12887(2007). CC -!- FUNCTION: Iota-conotoxins bind to voltage-gated sodium channels and act CC as agonists by shifting the voltage-dependence of activation to more CC hyperpolarized levels. This toxin acts on Nav1.6/SCN8A > Nav1.2/SCN2A > CC Nav1.7/SCN9A sodium channels. Produces general excitatory symptoms upon CC intracorporeal injection and repetitive action potentials in the frog CC cutaneous pectoris muscle. Natural peptide (with D-Phe) is active on CC nerve, but not on muscle. Synthetic peptide (with L-Phe) is not active CC on both nerve and muscle. {ECO:0000269|PubMed:17696362, CC ECO:0000269|PubMed:18486102}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. CC -!- DOMAIN: The cysteine framework is XI (C-C-CC-CC-C-C). CC -!- PTM: The natural D-Phe-44 form of the peptide is more potent than the CC L-Phe-44 form. CC -!- MASS SPECTROMETRY: Mass=3816.7; Method=LSI; CC Evidence={ECO:0000269|PubMed:12694387}; CC -!- MISCELLANEOUS: Does not have effect on sodium channels Nav1.1/SCN1A, CC Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A and on potassium channels CC Kv7.2/KCNQ2, Kv7.3/KCNQ3, Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, CC Kv1.5/KCNA5 and Kv1.6/KCNA6 (PubMed:18486102, PubMed:17696362). CC {ECO:0000305|PubMed:17696362, ECO:0000305|PubMed:18486102}. CC -!- SIMILARITY: Belongs to the conotoxin I1 superfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY208959; AAP41541.1; -; mRNA. DR PDB; 2JRY; NMR; -; A=1-46. DR PDB; 2JTU; NMR; -; A=1-38. DR PDB; 2P4L; NMR; -; A=1-46. DR PDBsum; 2JRY; -. DR PDBsum; 2JTU; -. DR PDBsum; 2P4L; -. DR SMR; Q7Z094; -. DR PRIDE; Q7Z094; -. DR ConoServer; 840; RXIA. DR EvolutionaryTrace; Q7Z094; -. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW. DR GO; GO:0009405; P:pathogenesis; IEA:InterPro. DR DisProt; DP01286; -. DR InterPro; IPR013141; Conotoxin-I_CS. DR InterPro; IPR012624; Toxin_19. DR Pfam; PF08088; Toxin_19; 1. DR PROSITE; PS60019; I_CONOTOXIN; 1. PE 1: Evidence at protein level; KW 3D-structure; D-amino acid; Direct protein sequencing; Disulfide bond; KW Hydroxylation; Ion channel impairing toxin; Neurotoxin; Secreted; Toxin; KW Voltage-gated sodium channel impairing toxin. FT CHAIN 1..46 FT /note="Iota-conotoxin RXIA" FT /id="PRO_0000086868" FT MOD_RES 2 FT /note="4-hydroxyproline; partial" FT /evidence="ECO:0000269|PubMed:12694387" FT MOD_RES 11 FT /note="4-hydroxyproline; partial" FT /evidence="ECO:0000269|PubMed:12694387" FT MOD_RES 29 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:12694387" FT MOD_RES 44 FT /note="D-phenylalanine" FT /evidence="ECO:0000269|PubMed:15561705" FT DISULFID 5..19 FT /evidence="ECO:0000269|PubMed:17696362, FT ECO:0000312|PDB:2JRY, ECO:0000312|PDB:2JTU, FT ECO:0000312|PDB:2P4L" FT DISULFID 12..22 FT /evidence="ECO:0000269|PubMed:17696362, FT ECO:0000312|PDB:2JRY, ECO:0000312|PDB:2JTU, FT ECO:0000312|PDB:2P4L" FT DISULFID 18..27 FT /evidence="ECO:0000269|PubMed:17696362, FT ECO:0000312|PDB:2JRY, ECO:0000312|PDB:2JTU, FT ECO:0000312|PDB:2P4L" FT DISULFID 21..38 FT /evidence="ECO:0000269|PubMed:17696362, FT ECO:0000312|PDB:2JRY, ECO:0000312|PDB:2JTU, FT ECO:0000312|PDB:2P4L" FT STRAND 8..10 FT /evidence="ECO:0000244|PDB:2P4L" FT STRAND 18..23 FT /evidence="ECO:0000244|PDB:2JRY" FT STRAND 26..29 FT /evidence="ECO:0000244|PDB:2JRY" FT STRAND 32..35 FT /evidence="ECO:0000244|PDB:2JRY" SQ SEQUENCE 46 AA; 4936 MW; 32C2812A24D82675 CRC64; GPSFCKADEK PCEYHADCCN CCLSGICAPS TNWILPGCST SSFFKI //