CRFA_CONVC
ID CRFA_CONVC Reviewed; 59 AA.
AC P0DOZ7;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 25-MAY-2022, entry version 16.
DE RecName: Full=Conorfamide-Vc1 {ECO:0000305};
DE Short=CNF-Vc1 {ECO:0000303|PubMed:25464369};
DE AltName: Full=Cono-RFamide-Vc1 {ECO:0000303|PubMed:25464369};
DE Flags: Precursor;
OS Conus victoriae (Queen Victoria cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX NCBI_TaxID=319920;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=24505301; DOI=10.1371/journal.pone.0087648;
RA Robinson S.D., Safavi-Hemami H., McIntosh L.D., Purcell A.W., Norton R.S.,
RA Papenfuss A.T.;
RT "Diversity of conotoxin gene superfamilies in the venomous snail, Conus
RT victoriae.";
RL PLoS ONE 9:E87648-E87648(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 26-43, IDENTIFICATION BY
RP MASS SPECTROMETRY, AMIDATION AT PHE-43, SYNTHESIS OF 26-43, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RC TISSUE=Venom, and Venom duct;
RX PubMed=25464369; DOI=10.1016/j.jprot.2014.11.003;
RA Robinson S.D., Safavi-Hemami H., Raghuraman S., Imperial J.S.,
RA Papenfuss A.T., Teichert R.W., Purcell A.W., Olivera B.M., Norton R.S.;
RT "Discovery by proteogenomics and characterization of an RF-amide
RT neuropeptide from cone snail venom.";
RL J. Proteomics 114:38-47(2015).
RN [3]
RP FUNCTION, SYNTHESIS OF 26-43, BIOASSAY, AND MUTAGENESIS OF 1-HIS--LEU-6 AND
RP 1-HIS--ARG-14.
RX PubMed=30243794; DOI=10.1016/j.toxicon.2018.09.002;
RA Espino S.S., Robinson S.D., Safavi-Hemami H., Gajewiak J., Yang W.,
RA Olivera B.M., Liu Q.;
RT "Conopeptides promote itch through human itch receptor hMgprX1.";
RL Toxicon 154:28-34(2018).
RN [4]
RP FUNCTION, AND SYNTHESIS OF 26-43.
RX PubMed=33764053; DOI=10.1021/acs.jnatprod.0c01297;
RA Bosse G.D., Urcino C., Watkins M., Florez Salcedo P., Kozel S., Chase K.,
RA Cabang A., Espino S.S., Safavi-Hemami H., Raghuraman S., Olivera B.M.,
RA Peterson R.T., Gajewiak J.;
RT "Discovery of a potent conorfamide from Conus episcopatus using a novel
RT zebrafish larvae assay.";
RL J. Nat. Prod. 84:1232-1243(2021).
CC -!- FUNCTION: This peptide activates human and mouse sensory neuron-
CC specific G-protein coupled receptors MRGPRX1 (PubMed:30243794). The
CC activity on human receptors has been measured (EC(50)=1.8 uM)
CC (PubMed:30243794). Compared with the agonist chloroquine (anti-malaria
CC drug), it is 200-fold more potent (PubMed:30243794). The peptide also
CC causes an increase in cytosolic calcium in a specific subset of DRG
CC neurons, and, in contrast to other Conus venom peptides, the peptide
CC also affects a large fraction of the non-neuronal cells
CC (PubMed:25464369). In vivo, when intracranially injected into mice, it
CC principally renders mice unable to move, and at very low doses, it
CC causes hyperactivity (PubMed:25464369). It also induces itch sensation,
CC since intradermal cheek injection into humanized transgenic mouse
CC (mouse MRGPRX1 replaced by human MRGPRX1) induces scratching
CC (PubMed:30243794). In vivo, when tested at high doses (10 uM) on
CC zebrafish larvae, it induces a range of behavioral effects ranging from
CC an early hypoactivity during the first hour of treatment to an increase
CC in movement during the following hours when the larvae are submitted to
CC strobe light phases (PubMed:33764053). {ECO:0000269|PubMed:25464369,
CC ECO:0000269|PubMed:30243794, ECO:0000269|PubMed:33764053}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25464369}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:25464369}.
CC -!- MISCELLANEOUS: The mature peptide does not contain cysteine residue.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the FARP (FMRFamide related peptide) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Paths of discomfort - Issue
CC 212 of March 2019;
CC URL="https://web.expasy.org/spotlight/back_issues/212/";
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DR EMBL; GAIH01000072; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; P0DOZ7; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW G-protein coupled receptor impairing toxin; Neurotoxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..25
FT /evidence="ECO:0000305|PubMed:25464369"
FT /id="PRO_0000439423"
FT PEPTIDE 26..43
FT /note="Conorfamide-Vc1"
FT /evidence="ECO:0000269|PubMed:25464369"
FT /id="PRO_0000439424"
FT PROPEP 45..59
FT /evidence="ECO:0000305|PubMed:25464369"
FT /id="PRO_0000439425"
FT REGION 32..39
FT /note="Positively charged region crucial for activity
FT against MRGPRX1 receptors"
FT /evidence="ECO:0000305|PubMed:30243794"
FT MOD_RES 43
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:25464369"
FT MUTAGEN 26..39
FT /note="Missing: Complete loss of activating potency on
FT MrgprX1 receptor."
FT /evidence="ECO:0000269|PubMed:30243794"
FT MUTAGEN 26..31
FT /note="Missing: No change in activity on MrgprX1 receptor."
FT /evidence="ECO:0000269|PubMed:30243794"
SQ SEQUENCE 59 AA; 6769 MW; B4113A72ED4CA1BE CRC64;
MSGRGFLLLA LLLLVTVEAT KVEKKHSGFL LAWSGPRNRF VRFGRRDMQS PLLSERLRL
