General Information

  • ID:  hor004549
  • Uniprot ID:  P0DQH7
  • Protein name:  Conorfamide As1a
  • Gene name:  NA
  • Organism:  Conus cancellatus (Cancellate cone) (Conus austini)
  • Family:  FARP (FMRFamide related peptide) family
  • Source:  animal
  • Expression:  Expressed by the venom duct.
  • Disease:  NA
  • Comments:  NA
  • Taxonomy:  Dauciconus (subgenus), Conus (genus), Conidae (family), Conoidea (superfamily), Neogastropoda (order), Caenogastropoda (subclass), Gastropoda (class), Mollusca (phylum), Lophotrochozoa, Spiralia, Protostomia, Bilateria, Eumetazoa, Metazoa (kingdom), Opisthokonta, Eukaryota (superkingdom), cellular organisms
  • GO MF:  GO:0030550 acetylcholine receptor inhibitor activity; GO:0090729 toxin activity; GO:0099106 ion channel regulator activity
  • GO BP:  GO:0035821 modulation of process of another organism
  • GO CC:  GO:0005576 extracellular region; GO:0035792 host cell postsynaptic membrane

Sequence Information

  • Sequence:  RIKKPIFAFPRF
  • Length:  12
  • Propeptide:  RIKKPIFAFPRF
  • Signal peptide:  NA
  • Modification:  T12 Phenylalanine amide
  • Glycosylation:  NA
  • Mutagenesis:  NA

Activity

  • Function:  Conorfamide As1a: this amidated form is active on both ASIC channels and nicotinic acetylcholine receptors (nAChRs) (PubMed:31028742). Shows a weak inhibition of peak current of rat ASIC1a and rat ASIC3 (PubMed:31028742). Inhibits desensitization of ASIC1a and to a lesser degree ASIC3 currents, resulting in a sustained opening of channels in the presence of low pH (PubMed:31028742). Inhibits with a slow reversibility human alpha-7/CHRNA7 nAChRs (IC(50)=737-4984 nM) and with rapid reversibility human alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChRs (IC(50)=215 nM) (PubMed:31028742).
  • Mechanism:  NA
  • Cross BBB:  NA
  • Target:  NA
  • Target Unid:  NA
  • IC50: human alpha-7/CHRNA7 nAChRs:737-4984 nM;human alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChRs :215 nM
  • EC50: NA
  • ED50: NA
  • kd: NA
  • Half life: NA

Structure

  • Disulfide bond:  NA
  • Structure ID:  NA

  • Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)
    •    hor004549_AF2.pdbhor004549_ESM.pdb

Physical Information

Mass: 171627 Formula: C76H118N20O13
Absent amino acids: CDEGHLMNQSTVWY Common amino acids: F
pI: 12.53 Basic residues: 4
Polar residues: 0 Hydrophobic residues: 6
Hydrophobicity: -6.67 Boman Index: -2035
Half-Life: 1 hour Half-Life Yeast: 2 min
Half-Life E.Coli: 2 min Aliphatic Index 73.33
Instability Index: 557.5 Extinction Coefficient cystines: 0
Absorbance 280nm: 0

Literature

  • PubMed ID:  31028742
  • Title:  Novel conorfamides from Conus austini venom modulate both nicotinic acetylcholine receptors and acid-sensing ion channels.