O16O3_CONST
ID O16O3_CONST Reviewed; 71 AA.
AC Q9XZK2; Q9NCV3;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 25-MAY-2022, entry version 94.
DE RecName: Full=Omega-conotoxin SO-3 {ECO:0000303|PubMed:14510617, ECO:0000303|PubMed:15880145, ECO:0000303|PubMed:26344359};
DE Short=SO3 {ECO:0000303|Ref.6};
DE Flags: Precursor;
OS Conus striatus (Striated cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=6493;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=10573284; DOI=10.1016/s0196-9781(99)00116-3;
RA Lu B.-S., Yu F., Zhao D., Huang P.-T., Huang C.-F.;
RT "Conopeptides from Conus striatus and Conus textile by cDNA cloning.";
RL Peptides 20:1139-1144(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 6-71.
RA Duda T.F., Palumbi S.R.;
RT "Molecular evolution of four-loop conotoxin precursors from fish-eating
RT Conus.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SYNTHESIS OF 45-70, AND ANALGESIC ACTIVITY.
RX PubMed=14510617; DOI=10.1021/np030099y;
RA Dai Q., Liu F., Zhou Y., Lu B.-S., Yu F., Huang P.-T.;
RT "The synthesis of SO-3, a conopeptide with high analgesic activity derived
RT from Conus striatus.";
RL J. Nat. Prod. 66:1276-1279(2003).
RN [4]
RP FUNCTION.
RX PubMed=15880145; DOI=10.1038/sj.bjp.0706223;
RA Wen L., Yang S., Qiao H., Liu Z., Zhou W., Zhang Y., Huang P.-T.;
RT "SO-3, a new O-superfamily conopeptide derived from Conus striatus,
RT selectively inhibits N-type calcium currents in cultured hippocampal
RT neurons.";
RL Br. J. Pharmacol. 145:728-739(2005).
RN [5]
RP FUNCTION, TOXIC DOSE, SYNTHESIS OF 46-70, AMIDATION AT CYS-70, MUTAGENESIS
RP OF 48-ALA--PRO-52 AND 56-ILE--ASN-59, AND BIOASSAY.
RX PubMed=26344359; DOI=10.1016/j.neuropharm.2015.08.047;
RA Wang F., Yan Z., Liu Z., Wang S., Wu Q., Yu S., Ding J., Dai Q.;
RT "Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA.";
RL Neuropharmacology 101:137-145(2016).
RN [6]
RP STRUCTURE BY NMR OF 46-70, AND DISULFIDE BONDS.
RA Yan Y.B., Tu G.Z., Luo X.C., Dai Q.Y., Huang P.-T., Zhang R.Q.;
RT "Three dimensional solution structure of omega-conotoxin SO3 determined by
RT NMR.";
RL Chin. Sci. Bull. 48:1097-1102(2003).
CC -!- FUNCTION: Omega-conotoxins act at presynaptic membranes, they bind and
CC block voltage-gated calcium channels (Cav). This peptide selectively
CC targets Cav2.2/CACNA1B (IC(50)=160 nM) voltage-gated calcium channels
CC (PubMed:26344359). When tested in mammals, this toxin displays an
CC analgesic potency similar to MVIIA in a range of acute and chronic pain
CC models in rodents, but has less adverse effects (tremor, diminution of
CC spontaneous locomotor activity and bad coordinated locomotion) compared
CC with identical dosages of MVIIA injected intrathecally.
CC {ECO:0000269|PubMed:15880145, ECO:0000269|PubMed:26344359}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05484}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C).
CC -!- TOXIC DOSE: LD(50) is >16 mg/kg by intramuscular injection into
CC goldfish (C.carassius). {ECO:0000269|PubMed:26344359}.
CC -!- MISCELLANEOUS: This toxin has no effect on R-type calcium currents,
CC voltage-gated sodium currents, delayed rectifier potassium currents and
CC transient outward potassium currents. {ECO:0000305|PubMed:15880145}.
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR EMBL; AF146348; AAD31908.1; -; mRNA.
DR EMBL; AF174242; AAF89906.1; -; Genomic_DNA.
DR PDB; 1FYG; NMR; -; A=46-70.
DR PDBsum; 1FYG; -.
DR AlphaFoldDB; Q9XZK2; -.
DR SMR; Q9XZK2; -.
DR ConoServer; 1216; SO3 precursor.
DR ConoServer; 864; SO3 precursor.
DR EvolutionaryTrace; Q9XZK2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR004214; Conotoxin.
DR InterPro; IPR012321; Conotoxin_omega-typ_CS.
DR Pfam; PF02950; Conotoxin; 1.
DR PROSITE; PS60004; OMEGA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Calcium channel impairing toxin; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Presynaptic neurotoxin;
KW Secreted; Signal; Toxin; Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..45
FT /evidence="ECO:0000250"
FT /id="PRO_0000034932"
FT PEPTIDE 46..70
FT /note="Omega-conotoxin SO-3"
FT /id="PRO_0000034933"
FT SITE 58
FT /note="Important for calcium channel binding"
FT /evidence="ECO:0000250|UniProtKB:P05484"
FT MOD_RES 70
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:26344359"
FT DISULFID 46..61
FT /evidence="ECO:0000269|Ref.6"
FT DISULFID 53..65
FT /evidence="ECO:0000269|Ref.6"
FT DISULFID 60..70
FT /evidence="ECO:0000269|Ref.6"
FT MUTAGEN 48..52
FT /note="AAGKP->GKGAK: 2.8-fold increase in inhibition of
FT Cav2.2; increase in efficacy to kill goldfish (LD(50) is
FT 11.6 mg/kg by intramuscular injection) (mutant omega-2)."
FT /evidence="ECO:0000269|PubMed:26344359"
FT MUTAGEN 56..59
FT /note="IAYN->LMYD: 4.3-fold decrease in inhibition of
FT Cav2.2; increase in efficacy to kill goldfish (LD(50) is
FT 5.20 mg/kg by intramuscular injection) (mutant omega-1)."
FT /evidence="ECO:0000269|PubMed:26344359"
FT CONFLICT 6
FT /note="M -> V (in Ref. 2; AAF89906)"
FT /evidence="ECO:0000305"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:1FYG"
SQ SEQUENCE 71 AA; 7628 MW; CE7070DCE3094D73 CRC64;
MKLTCMVIVA VLLLTACQLI TADDSRGTQK HRTLRSKTKL SMSTRCKAAG KPCSRIAYNC
CTGSCRSGKC G
