General Information

  • ID:  hor004551
  • Uniprot ID:  P0DOZ7
  • Protein name:  Conorfamide-Vc1
  • Gene name:  NA
  • Organism:  Conus victoriae (Queen Victoria cone)
  • Family:  FARP (FMRFamide related peptide) family
  • Source:  animal
  • Expression:  Expressed by the venom duct.
  • Disease:  NA
  • Comments:  NA
  • Taxonomy:  Cylinder (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:0090729 toxin activity
  • GO BP:  GO:0035821 modulation of process of another organism
  • GO CC:  GO:0005576 extracellular region

Sequence Information

  • Sequence:  HSGFLLAWSGPRNRFVRF
  • Length:  18
  • Propeptide:  MSGRGFLLLALLLLVTVEATKVEKKHSGFLLAWSGPRNRFVRFGRRDMQSPLLSERLRL
  • Signal peptide:  MSGRGFLLLALLLLVTVEA
  • Modification:  T18 Phenylalanine amide
  • Glycosylation:  NA
  • Mutagenesis:  1-14Missing: Complete loss of activating potency on MrgprX1 receptor.; 1-6Missing: Complete loss of activating potency on MrgprX1 receptor.

Activity

  • Function:  This peptide activates human and mouse sensory neuron-specific G-protein coupled receptors MRGPRX1 (PubMed:30243794). The activity on human receptors has been measured (EC(50)=1.8 uM) (PubMed:30243794). Compared with the agonist chloroquine (anti-malaria drug), it is 200-fold more potent (PubMed:30243794). The peptide also causes an increase in cytosolic calcium in a specific subset of DRG neurons, and, in contrast to other Conus venom peptides, the peptide also affects a large fraction of the non-neuronal cells (PubMed:25464369). In vivo, when intracranially injected into mice, it principally renders mice unable to move, and at very low doses, it causes hyperactivity (PubMed:25464369). It also induces itch sensation, since intradermal cheek injection into humanized transgenic mouse (mouse MRGPRX1 replaced by human MRGPRX1) induces scratching (PubMed:30243794). In vivo, when tested at high doses (10 uM) on zebrafish larvae, it induces a range of behavioral effects ranging from an early hypoactivity during the first hour of treatment to an increase in movement during the following hours when the larvae are submitted to strobe light phases (PubMed:33764053).
  • Mechanism:  The mature peptide does not contain cysteine residue.
  • Cross BBB:  NA
  • Target:  NA
  • Target Unid:  NA
  • IC50: NA
  • EC50: 1.8*10(-6)M
  • ED50: NA
  • kd: NA
  • Half life: NA

Structure

  • Disulfide bond:  NA
  • Structure ID:  AF-P0DOZ7-F1(AlphaFold_DB_ID)

  • 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)
    •    hor004551_AF2.pdbhor004551_ESM.pdb

Physical Information

Mass: 245086 Formula: C101H147N31O22
Absent amino acids: CDEIKMQTY Common amino acids: FR
pI: 12.8 Basic residues: 4
Polar residues: 5 Hydrophobic residues: 8
Hydrophobicity: -17.22 Boman Index: -3402
Half-Life: 3.5 hour Half-Life Yeast: 10 min
Half-Life E.Coli: >10 hour Aliphatic Index 65
Instability Index: 1211.11 Extinction Coefficient cystines: 5500
Absorbance 280nm: 323.53

Literature

  • PubMed ID:  25464369
  • Title:  Discovery by Proteogenomics and Characterization of an RF-amide Neuropeptide From Cone Snail Venom