ID CI11A_CONRA Reviewed; 46 AA. AC Q7Z094; DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 02-OCT-2007, entry version 28. DE Iota-conotoxin RXIA (r11a) (R11.6). OS Conus radiatus (Rayed cone). OC Eukaryota; Metazoa; Mollusca; Gastropoda; Orthogastropoda; OC Apogastropoda; Caenogastropoda; Sorbeoconcha; Hypsogastropoda; OC 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). CC -!- FUNCTION: Binds sodium channels (Nav1.6/SCN8A) and shifts the CC voltage of activation toward more negative potentials thereby CC affecting sodium channel activation. Has no effect on Kv7.2/KCNQ2, CC Kv7.3/KCNQ3, Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5 CC and Kv1.6/KCNA6. Produces general excitatory symptoms upon CC intracorporeal injection and repetitive action potentials in the CC frog cutaneous pectoris muscle. Natural peptide (with D-Phe) is CC active on nerve, but not on muscle. Synthetic peptide (with L-Phe) CC is not active on both nerve and muscle. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot' CC structurally defines this protein as a knottin. CC -!- PTM: The natural D-Phe form of the peptide is more potent than the CC L-Phe form. CC -!- MASS SPECTROMETRY: Mass=3816.7; Method=LSI; Range=1-46; CC Source=PubMed:12694387; CC -!- SIMILARITY: Belongs to the conotoxin I1 superfamily. Iota-type CC family. 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 InterPro; IPR013141; Conotoxin_I. DR InterPro; IPR012624; Toxin_19. DR Pfam; PF08088; Toxin_19; 1. DR PROSITE; PS60019; I_CONOTOXIN; 1. PE 1: Evidence at protein level; KW Bromination; D-amino acid; Direct protein sequencing; Hydroxylation; KW Ionic channel inhibitor; Knottin; Neurotoxin; Secreted; KW 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 SQ SEQUENCE 46 AA; 4936 MW; 32C2812A24D82675 CRC64; GPSFCKADEK PCEYHADCCN CCLSGICAPS TNWILPGCST SSFFKI //