I1BA_CONRA
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 25-MAY-2022, entry version 81.
DE RecName: Full=Iota-conotoxin RXIA;
DE AltName: Full=R11.6;
DE AltName: Full=r11a;
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], 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 OF PUBMED:17696362.
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}.
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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 AlphaFoldDB; Q7Z094; -.
DR SMR; Q7Z094; -.
DR ConoServer; 840; RXIA.
DR EvolutionaryTrace; Q7Z094; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
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:0007829|PDB:2P4L"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:2JRY"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:2JRY"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:2JRY"
SQ SEQUENCE 46 AA; 4936 MW; 32C2812A24D82675 CRC64;
GPSFCKADEK PCEYHADCCN CCLSGICAPS TNWILPGCST SSFFKI
