CRF2_CONCF
ID CRF2_CONCF Reviewed; 12 AA.
AC P0DQH8;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 23-FEB-2022, entry version 6.
DE RecName: Full=Conorfamide-As2 {ECO:0000305|PubMed:31028742};
DE AltName: Full=Conorfamide-As2a {ECO:0000303|PubMed:31028742};
DE Short=CNF-As2a {ECO:0000250|UniProtKB:P0DOZ7};
DE Short=Cono-RFamide-As2a {ECO:0000250|UniProtKB:P0DOZ7};
DE AltName: Full=Conorfamide-As2b {ECO:0000303|PubMed:31028742};
DE Short=CNF-As2b {ECO:0000250|UniProtKB:P0DOZ7};
DE Short=Cono-RFamide-As2b {ECO:0000250|UniProtKB:P0DOZ7};
OS Conus cancellatus (Cancellate cone) (Conus austini).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Dauciconus.
OX NCBI_TaxID=289020;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AMIDATION AT PHE-12, MASS
RP SPECTROMETRY, AND SYNTHESIS.
RC TISSUE=Venom;
RX PubMed=31028742; DOI=10.1016/j.bcp.2019.04.025;
RA Jin A.H., Cristofori-Armstrong B., Rash L.D., Roman-Gonzalez S.A.,
RA Espinosa R.A., Lewis R.J., Alewood P.F., Vetter I.;
RT "Novel conorfamides from Conus austini venom modulate both nicotinic
RT acetylcholine receptors and acid-sensing ion channels.";
RL Biochem. Pharmacol. 164:342-348(2019).
CC -!- FUNCTION: Conorfamide As2a: this amidated form is active on both ASIC
CC channels and nicotinic acetylcholine receptors (nAChRs)
CC (PubMed:31028742). Potentiates ASIC1a (EC(50)=10.9 uM)
CC (PubMed:31028742). Inhibits desensitization of ASIC1a and to a lesser
CC degree ASIC3 currents, resulting in a sustained opening of channels in
CC the presence of low pH (PubMed:31028742). Inhibits with a slow
CC reversibility human alpha-7/CHRNA7 nAChRs (IC(50)=689-3867 nM) and with
CC a rapid reversibility human alpha-1-beta-1-delta-epsilon (CHRNA1-
CC CHRNB1-CHRND-CHRNE) nAChRs (IC(50)=208 nM) (PubMed:31028742).
CC {ECO:0000269|PubMed:31028742}.
CC -!- FUNCTION: Conorfamide As2b: this non-amidated form is only weakly
CC active on both ASIC channels and nicotinic acetylcholine receptors
CC (nAChRs) (PubMed:31028742). Shows a very weak inhibition of peak
CC current of rat ASIC1a and ASIC3 (PubMed:31028742). No inhibition or
CC very weak desensitization of both rat ASIC1a and ASIC3 are observed
CC (PubMed:31028742). Reversibly inhibits both human alpha-7/CHRNA7 nAChRs
CC (IC(50)=2971-7036 nM) and human alpha-1-beta-1-delta-epsilon (CHRNA1-
CC CHRNB1-CHRND-CHRNE) nAChRs (IC(50)=707 nM) (PubMed:31028742).
CC {ECO:0000269|PubMed:31028742}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31028742}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:31028742}.
CC -!- PTM: Both amidated and non-amidated conorfamides As2 are found in the
CC venom. Amidation is important since amidated peptide is more active.
CC {ECO:0000269|PubMed:31028742}.
CC -!- MASS SPECTROMETRY: Mass=1659.97; Method=MALDI; Note=Conorfamide As2a.;
CC Evidence={ECO:0000269|PubMed:31028742};
CC -!- MASS SPECTROMETRY: Mass=1661.02; Method=MALDI; Note=Conorfamide As2b.;
CC Evidence={ECO:0000269|PubMed:31028742};
CC -!- SIMILARITY: Belongs to the FARP (FMRFamide related peptide) family.
CC {ECO:0000305}.
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DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Proton-gated sodium channel impairing toxin;
KW Secreted; Toxin.
FT PEPTIDE 1..12
FT /note="Conorfamide-As2"
FT /evidence="ECO:0000269|PubMed:31028742"
FT /id="PRO_0000447683"
FT MOD_RES 12
FT /note="Phenylalanine amide; in Conorfamide As2a"
FT /evidence="ECO:0000269|PubMed:31028742"
SQ SEQUENCE 12 AA; 1548 MW; 3134D70357D9C047 CRC64;
RIRKPIFAFP RF
