ID   COS_CONTE               Reviewed;           8 AA.
AC   P0DL71;
DT   05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2017, sequence version 1.
DT   23-FEB-2022, entry version 10.
DE   RecName: Full=Conorfamide Tx1.3 {ECO:0000305};
DE   AltName: Full=AIVGRPRFamide {ECO:0000303|PubMed:28396446};
DE            Short=AIVGRPRFa {ECO:0000303|PubMed:28396446};
DE   AltName: Full=Cono-RFamide CNF-Tx1.3 {ECO:0000303|PubMed:28396446};
DE   Contains:
DE     RecName: Full=CNF-Tx1.2 {ECO:0000303|PubMed:28396446};
DE     AltName: Full=VGRPRFamide {ECO:0000303|PubMed:28396446};
DE              Short=VGRPRFa {ECO:0000303|PubMed:28396446};
DE   Contains:
DE     RecName: Full=CNF-Tx1.1 {ECO:0000303|PubMed:28396446};
DE     AltName: Full=RPRFamide {ECO:0000303|PubMed:28396446};
DE              Short=RPRFa {ECO:0000303|PubMed:28396446};
OS   Conus textile (Cloth-of-gold cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX   NCBI_TaxID=6494;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, BIOASSAY, AMIDATION AT PHE-8, SUBCELLULAR
RP   LOCATION, AND SYNTHESIS.
RC   TISSUE=Venom;
RX   PubMed=28396446; DOI=10.1073/pnas.1616232114;
RA   Reimers C., Lee C.H., Kalbacher H., Tian Y., Hung C.H., Schmidt A.,
RA   Prokop L., Kauferstein S., Mebs D., Chen C.C., Gruender S.;
RT   "Identification of a cono-RFamide from the venom of Conus textile that
RT   targets ASIC3 and enhances muscle pain.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:E3507-E3515(2017).
CC   -!- FUNCTION: [CNF-Tx1.1]: Potentiates ASIC3 currents (homotrimer and
CC       ASIC1a-ASIC3, ASIC1b-ASIC3, ASIC2a-ASIC3 and ASIC2b-ASIC3
CC       heterotrimers) (PubMed:28396446). It increases the peak current
CC       amplitude of ASIC3 homotrimer by 1.48-fold (PubMed:28396446). In
CC       addition, it slows the desensitization kinetics of ASIC3 (homotrimer
CC       and heterotrimer-containing ASIC3) (PubMed:28396446). The current
CC       amplitude at the end of a 10-second proton pulse of ASIC3 homotrimer is
CC       26% instead of 1% without the peptide (PubMed:28396446). It strongly
CC       acts by binding to the channel in the closed state (PubMed:28396446).
CC       It shows a higher affinity for ASIC3 homotrimers than does CNF-Tx1.2
CC       (PubMed:28396446). It changes the apparent proton affinity of ASIC3 (to
CC       higher pH for potentiation and to lower pH for desensitization)
CC       (PubMed:28396446). It competes with FMRFamide (AC P69145) for a common
CC       binding site (PubMed:28396446). In vivo, intramuscular injection into
CC       mice enhances acid-induced muscle pain (PubMed:28396446).
CC       {ECO:0000269|PubMed:28396446}.
CC   -!- FUNCTION: [CNF-Tx1.2]: Potentiates ASIC3 (homotrimer) currents
CC       (PubMed:28396446) and heterotrimer-containing ASIC3 (Probable). It
CC       increases the peak current amplitude of ASIC3 homotrimer by 1.2-fold
CC       (PubMed:28396446). In addition, it slows the desensitization kinetics
CC       of ASIC3 (the current amplitude at the end of a 10-second proton pulse
CC       is 40% instead of 1% without the peptide) (PubMed:28396446). It shows a
CC       lower affinity for ASIC3 than CNF-Tx1.1 (PubMed:28396446). In vivo,
CC       intramuscular injection into mice enhances acid-induced muscle pain
CC       (Probable). {ECO:0000269|PubMed:28396446, ECO:0000305}.
CC   -!- FUNCTION: CNF-Tx1.3: Potentiates ASIC3 (homotrimer) currents
CC       (PubMed:28396446) and heterotrimer-containing ASIC3 (Probable). Is less
CC       potent than CNF-Tx1.1 and CNF-Tx1.2 (PubMed:28396446). In addition, it
CC       slows the desensitization kinetics of ASIC3 (Probable). In vivo,
CC       intramuscular injection into mice enhances acid-induced muscle pain
CC       (Probable). {ECO:0000269|PubMed:28396446, ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28396446}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:28396446}.
CC   -!- PTM: The amidation of Phe-8 is essential for rat ASIC3 current
CC       potentiation. A synthetic peptide with Phe-8 not amidated does not
CC       potentiate ASIC3 current. {ECO:0000269|PubMed:28396446}.
CC   -!- SIMILARITY: Belongs to the NPY family. {ECO:0000305|PubMed:28396446}.
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DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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   Amidation; Direct protein sequencing; Ion channel impairing toxin;
KW   Proton-gated sodium channel impairing toxin; Secreted; Toxin.
FT   PEPTIDE         1..8
FT                   /note="Conorfamide Tx1.3"
FT                   /evidence="ECO:0000269|PubMed:28396446"
FT                   /id="PRO_0000440942"
FT   PEPTIDE         3..8
FT                   /note="CNF-Tx1.2"
FT                   /evidence="ECO:0000269|PubMed:28396446"
FT                   /id="PRO_0000440943"
FT   PEPTIDE         5..8
FT                   /note="CNF-Tx1.1"
FT                   /evidence="ECO:0000269|PubMed:28396446"
FT                   /id="PRO_0000440944"
FT   MOD_RES         8
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:28396446"
SQ   SEQUENCE   8 AA;  915 MW;  9CD417740862C05D CRC64;
     AIVGRPRF