ID   CRF1_CONCF              Reviewed;          12 AA.
AC   P0DQH7;
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-As1 {ECO:0000305|PubMed:31028742};
DE   AltName: Full=Conorfamide-As1a {ECO:0000303|PubMed:31028742};
DE            Short=CNF-As1a {ECO:0000250|UniProtKB:P0DOZ7};
DE            Short=Cono-RFamide-As1a {ECO:0000250|UniProtKB:P0DOZ7};
DE   AltName: Full=Conorfamide-As1b {ECO:0000303|PubMed:31028742};
DE            Short=CNF-As1b {ECO:0000250|UniProtKB:P0DOZ7};
DE            Short=Cono-RFamide-As1b {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 As1a: this amidated form is active on both ASIC
CC       channels and nicotinic acetylcholine receptors (nAChRs)
CC       (PubMed:31028742). Shows a weak inhibition of peak current of rat
CC       ASIC1a and rat ASIC3 (PubMed:31028742). Inhibits desensitization of
CC       ASIC1a and to a lesser degree ASIC3 currents, resulting in a sustained
CC       opening of channels in the presence of low pH (PubMed:31028742).
CC       Inhibits with a slow reversibility human alpha-7/CHRNA7 nAChRs
CC       (IC(50)=737-4984 nM) and with rapid reversibility human alpha-1-beta-1-
CC       delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChRs (IC(50)=215 nM)
CC       (PubMed:31028742). {ECO:0000269|PubMed:31028742}.
CC   -!- FUNCTION: Conorfamide As1b: this non-amidated form is only weakly
CC       active on both ASIC channels and nicotinic acetylcholine receptors
CC       (nAChRs) (PubMed:31028742). Shows a weak inhibition of peak current of
CC       rat ASIC1a (PubMed:31028742). Shows a very weak inhibition of peak
CC       current of rat ASIC3 (PubMed:31028742). No inhibition of
CC       desensitization on both rat ASIC1a and ASIC3 are observed
CC       (PubMed:31028742). Reversibly inhibits both human alpha-7/CHRNA7 nAChRs
CC       (IC(50)=2029-8464 nM) and human alpha-1-beta-1-delta-epsilon (CHRNA1-
CC       CHRNB1-CHRND-CHRNE) nAChRs (IC(50)=820 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 As1 are found in the
CC       venom. Amidation is important since amidated peptide is more active.
CC       {ECO:0000269|PubMed:31028742}.
CC   -!- MASS SPECTROMETRY: Mass=1631.97; Method=MALDI; Note=Conorfamide As1a.;
CC       Evidence={ECO:0000269|PubMed:31028742};
CC   -!- MASS SPECTROMETRY: Mass=1633.01; Method=MALDI; Note=Conorfamide As1b.;
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-As1"
FT                   /evidence="ECO:0000269|PubMed:31028742"
FT                   /id="PRO_0000447682"
FT   MOD_RES         12
FT                   /note="Phenylalanine amide; in Conorfamide As1a"
FT                   /evidence="ECO:0000269|PubMed:31028742"
SQ   SEQUENCE   12 AA;  1520 MW;  312BEA0357D9C047 CRC64;
     RIKKPIFAFP RF