O168_CONBU
ID O168_CONBU Reviewed; 50 AA.
AC P0CY66;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 25-MAY-2022, entry version 28.
DE RecName: Full=Omega-conotoxin Bu8 {ECO:0000303|PubMed:34589389};
DE Flags: Precursor; Fragment;
OS Conus bullatus (Bubble cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Textilia.
OX NCBI_TaxID=89438;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=21266071; DOI=10.1186/1471-2164-12-60;
RA Hu H., Bandyopadhyay P.K., Olivera B.M., Yandell M.;
RT "Characterization of the Conus bullatus genome and its venom-duct
RT transcriptome.";
RL BMC Genomics 12:60-60(2011).
RN [2]
RP FUNCTION, SYNTHESIS OF 25-49, PROBABLE AMIDATION AT CYS-49, DISULFIDE BOND,
RP STRUCTURE BY NMR OF 25-49, MUTAGENESIS OF ARG-27; SER-30; SER-31; ARG-33;
RP THR-35; SER-36 AND ASN-46, AND TOXIC DOSE.
RX PubMed=34589389; DOI=10.1016/j.apsb.2021.03.001;
RA Chen J., Liu X., Yu S., Liu J., Chen R., Zhang Y., Jiang L., Dai Q.;
RT "A novel omega-conotoxin Bu8 inhibiting N-type voltage-gated calcium
RT channels displays potent analgesic activity.";
RL Acta Pharm. Sin. B (APSB) 11:2685-2693(2021).
CC -!- FUNCTION: Omega-conotoxins act at presynaptic membranes, they bind and
CC block voltage-gated calcium channels (Cav). This toxin selectively and
CC potently inhibits depolarization-activated rat Cav2.2/CACNA1B currents
CC (IC(50)=89 nM), when coexpressed with alpha-2/delta-1 (CACNA2D1) and
CC beta-3 (CACNB3) subunits. In vivo, is lethal to fish and displays
CC potent analgesic activity in mice pain models of hot plate and acetic
CC acid writhing but has fewer side effects on mouse motor function and
CC lower toxicity in goldfish. Shows higher or similar analgesic activity
CC in the pain models mentioned above compared to MVIIA, and lower side
CC effects. In addition, it blocks Cav2.2/CACNA1B more rapidly than MVIIA
CC and also dissociates more rapidly. {ECO:0000269|PubMed:34589389}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:21266071}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:21266071}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:34589389}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC -!- TOXIC DOSE: LD(50) is 0.31 (0.22-0.41) mg/kg by intramuscular injection
CC into goldfish (after 4 hours). {ECO:0000269|PubMed:34589389}.
CC -!- MISCELLANEOUS: Shows very weak activity on Cav2.1/CACNA1A (27.36%
CC current inhibition at 10 uM) and Cav1.1/CACNA1S (2.82% current
CC inhibition at 10 uM), and no activity on sodium (Nav) and potassium
CC (Kv) channels in rat DRG neurons. {ECO:0000269|PubMed:34589389}.
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR PDB; 5ZNU; NMR; -; A=25-49.
DR PDBsum; 5ZNU; -.
DR AlphaFoldDB; P0CY66; -.
DR BMRB; P0CY66; -.
DR SMR; P0CY66; -.
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; IPR012321; Conotoxin_omega-typ_CS.
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; Secreted; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin.
FT SIGNAL <1..1
FT /evidence="ECO:0000255"
FT PROPEP 2..24
FT /evidence="ECO:0000305|PubMed:34589389"
FT /id="PRO_0000409948"
FT PEPTIDE 25..49
FT /note="Omega-conotoxin Bu8"
FT /evidence="ECO:0000305|PubMed:34589389"
FT /id="PRO_0000409949"
FT SITE 27
FT /note="Key residue for inhibiting Cav2.2/CACNA1B"
FT /evidence="ECO:0000269|PubMed:34589389"
FT SITE 33
FT /note="Key residue for inhibiting Cav2.2/CACNA1B"
FT /evidence="ECO:0000269|PubMed:34589389"
FT SITE 35
FT /note="Key residue for inhibiting Cav2.2/CACNA1B"
FT /evidence="ECO:0000269|PubMed:34589389"
FT MOD_RES 49
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:34589389"
FT DISULFID 25..40
FT /evidence="ECO:0000269|PubMed:34589389"
FT DISULFID 32..44
FT /evidence="ECO:0000269|PubMed:34589389"
FT DISULFID 39..49
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 27
FT /note="R->A: Decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 27
FT /note="R->G: Small decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 30
FT /note="S->A: Small increase in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 31
FT /note="S->A: No change in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 33
FT /note="R->A: Important decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 33
FT /note="R->S: Small increase in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 35
FT /note="T->A: Important decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 35
FT /note="T->L: Decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 36
FT /note="S->A: Small decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 36
FT /note="S->M: No change in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 46
FT /note="N->A: No change in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT MUTAGEN 46
FT /note="N->S: Small decrease in ability to inhibit
FT Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:34589389"
FT NON_TER 1
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:5ZNU"
SQ SEQUENCE 50 AA; 5511 MW; 9CEE3B2F28BC263F CRC64;
AEDSRGTQLH RALRKATKLS ESTRCKRKGS SCRRTSYDCC TGSCRNGKCG
