ID CI1BA_CONRA Reviewed; 46 AA. AC Q7Z094; DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 03-MAY-2011, entry version 45. DE RecName: Full=Iota-conotoxin RXIA; DE AltName: Full=R11.6; DE AltName: Full=r11a; OS Conus radiatus (Rayed cone). OC Eukaryota; Metazoa; Mollusca; Gastropoda; Caenogastropoda; OC Hypsogastropoda; Neogastropoda; Conoidea; Conidae; Conus. OX NCBI_TaxID=61198; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE, AND MASS SPECTROMETRY. RC TISSUE=Venom, and Venom duct; RX PubMed=12694387; RA Jimenez E.C., Shetty R.P., Lirazan M., Rivier J., Walker C., RA Abogadie F.C., 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 RT D-amino acid in an excitatory peptide."; RL J. Biol. Chem. 280:4247-4253(2005). RN [3] RP FUNCTION, SYNTHESIS (D-PHE AND L-PHE), STRUCTURE BY NMR, AND DISULFIDE RP BONDS. RX PubMed=17696362; DOI=10.1021/bi700797f; RA Buczek O., Wei D., Babon J.J., Yang X., Fiedler B., Chen P., RA Yoshikami D., Olivera B.M., Bulaj G., Norton R.S.; RT "Structure and sodium channel activity of an excitatory I(1)- RT superfamily conotoxin."; RL Biochemistry 46:9929-9940(2007). RN [4] RP ERRATUM. RA Buczek O., Wei D., Babon J.J., Yang X., Fiedler B., Chen P., RA Yoshikami D., Olivera B.M., Bulaj G., Norton R.S.; RL Biochemistry 46:12887-12887(2007). RN [5] RP FUNCTION, AND TOXIN TARGET. 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 RT of voltage-gated sodium channels Na(V)1.2, 1.6 and 1.7."; RL Biochem. Pharmacol. 75:2334-2344(2008). CC -!- FUNCTION: Iota-conotoxins bind to voltage-gated sodium channels CC and act as agonists by shifting the voltage-dependence of CC activation to more hyperpolarized levels. This toxin acts on CC Nav1.6/SCN8A > Nav1.2/SCN2A > Nav1.7/SCN9A sodium channels. It has CC no effect on other sodium channels (Nav1.1/SCN1A, Nav1.3/SCN3A, CC 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). Produces general excitatory symptoms CC upon intracorporeal injection and repetitive action potentials in CC the frog cutaneous pectoris muscle. Natural peptide (with D-Phe) CC is active on nerve, but not on muscle. Synthetic peptide (with L- CC Phe) is not active on both nerve and muscle. 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 CC the L-Phe-44 form. CC -!- MASS SPECTROMETRY: Mass=3816.7; Method=LSI; Range=1-46; CC Source=PubMed:12694387; CC -!- SIMILARITY: Belongs to the conotoxin I1 superfamily. 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 ProteinModelPortal; Q7Z094; -. DR SMR; Q7Z094; 1-46. DR ConoServer; 840; RXIA. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW. 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; Bromination; D-amino acid; Direct protein sequencing; KW Disulfide bond; Hydroxylation; Ionic channel inhibitor; Neurotoxin; KW Secreted; Sodium channel inhibitor; Toxin. FT CHAIN 1 46 Iota-conotoxin RXIA. FT /FTId=PRO_0000086868. FT MOD_RES 2 2 4-hydroxyproline; partial. FT MOD_RES 11 11 4-hydroxyproline; partial. FT MOD_RES 29 29 4-hydroxyproline. FT MOD_RES 33 33 6'-bromotryptophan. FT MOD_RES 44 44 D-phenylalanine. FT DISULFID 5 19 FT DISULFID 12 22 FT DISULFID 18 27 FT DISULFID 21 38 FT STRAND 8 10 FT STRAND 13 22 SQ SEQUENCE 46 AA; 4936 MW; 32C2812A24D82675 CRC64; GPSFCKADEK PCEYHADCCN CCLSGICAPS TNWILPGCST SSFFKI //