FLP18_CAEEL
ID FLP18_CAEEL Reviewed; 208 AA.
AC Q9N4V0; Q86MI4;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=FMRFamide-like neuropeptide 18;
DE Contains:
DE RecName: Full=EMPGVLRF-amide;
DE Contains:
DE RecName: Full=SVPGVLRF-amide 1;
DE Contains:
DE RecName: Full=SVPGVLRF-amide 2;
DE Contains:
DE RecName: Full=EIPGVLRF-amide;
DE Contains:
DE RecName: Full=SEVPGVLRF-amide;
DE Contains:
DE RecName: Full=DVPGVLRF-amide;
DE Contains:
DE RecName: Full=SVPGVLRF-amide 3;
DE Flags: Precursor;
GN Name=flp-18 {ECO:0000312|WormBase:Y48D7A.2};
GN ORFNames=Y48D7A.2 {ECO:0000312|WormBase:Y48D7A.2};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000269|PubMed:9851916};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 86-93, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16187307; DOI=10.1002/neu.20201;
RA Papaioannou S., Marsden D., Franks C.J., Walker R.J., Holden-Dye L.;
RT "Role of a FMRFamide-like family of neuropeptides in the pharyngeal nervous
RT system of Caenorhabditis elegans.";
RL J. Neurobiol. 65:304-319(2005).
RN [3] {ECO:0000305}
RP PROTEIN SEQUENCE OF 104-111; 122-129 AND 198-205, FUNCTION, MASS
RP SPECTROMETRY, AND AMIDATION AT PHE-93; PHE-111; PHE-129; PHE-147; PHE-169;
RP PHE-180 AND PHE-205.
RX PubMed=11527423; DOI=10.1006/bbrc.2001.5524;
RA Marks N.J., Shaw C., Halton D.W., Thompson D.P., Geary T.G., Li C.,
RA Maule A.G.;
RT "Isolation and preliminary biological assessment of AADGAPLIRFamide and
RT SVPGVLRFamide from Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 286:1170-1176(2001).
RN [4] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14555955; DOI=10.1038/nn1140;
RA Rogers C., Reale V., Kim K., Chatwin H., Li C., Evans P., de Bono M.;
RT "Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related
RT peptide activation of NPR-1.";
RL Nat. Neurosci. 6:1178-1185(2003).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=23764289; DOI=10.1016/j.neuron.2013.04.002;
RA Choi S., Chatzigeorgiou M., Taylor K.P., Schafer W.R., Kaplan J.M.;
RT "Analysis of NPR-1 reveals a circuit mechanism for behavioral quiescence in
RT C. elegans.";
RL Neuron 78:869-880(2013).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=23658528; DOI=10.1371/journal.pgen.1003472;
RA Stawicki T.M., Takayanagi-Kiya S., Zhou K., Jin Y.;
RT "Neuropeptides function in a homeostatic manner to modulate excitation-
RT inhibition imbalance in C. elegans.";
RL PLoS Genet. 9:E1003472-E1003472(2013).
RN [7] {ECO:0000305}
RP REVIEW OF FUNCTION.
RX PubMed=25804345; DOI=10.1016/j.tig.2015.02.009;
RA Sterken M.G., Snoek L.B., Kammenga J.E., Andersen E.C.;
RT "The laboratory domestication of Caenorhabditis elegans.";
RL Trends Genet. 31:224-231(2015).
RN [8]
RP FUNCTION.
RX PubMed=28662030; DOI=10.1371/journal.pbio.2002047;
RA Hoang H.D., Miller M.A.;
RT "Chemosensory and hyperoxia circuits in C. elegans males influence sperm
RT navigational capacity.";
RL PLoS Biol. 15:E2002047-E2002047(2017).
CC -!- FUNCTION: FMRFamide-like neuropeptides (PubMed:14555955,
CC PubMed:23658528). Ligand to G-protein coupled receptor npr-1
CC (PubMed:14555955). Involved in modulating locomotion quiescence during
CC the sleep-like state called lethargus which occurs during molting
CC between larval and adult stages, acting via npr-1 (PubMed:23764289).
CC Together with flp-1, plays a homeostatic role by acting on the
CC GABAergic neural transmission at neuromuscular junctions to prevent
CC overexcitation of the locomotor circuit (PubMed:23658528). Plays a role
CC in the navigational capacity of sperm and the targeting of sperm
CC derived from males to the fertilization site in the uterus of
CC hermaphrodites (PubMed:28662030). {ECO:0000269|PubMed:14555955,
CC ECO:0000269|PubMed:23658528, ECO:0000269|PubMed:23764289,
CC ECO:0000269|PubMed:28662030}.
CC -!- FUNCTION: SVPGVLRF-amide: Excites muscle tension.
CC {ECO:0000269|PubMed:11527423}.
CC -!- FUNCTION: [EMPGVLRF-amide]: Activates the G-protein coupled receptor
CC npr-1 more effectively than other flp-18 peptides (PubMed:14555955).
CC Inhibits the activity of dissected pharyngeal myogenic muscle system.
CC {ECO:0000269|PubMed:14555955, ECO:0000269|PubMed:16187307}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in head neurons and weakly in ventral
CC nerve cord (PubMed:23658528). Expressed in the interneurons AVA, AIY
CC and RIG, the motor neuron RIM and the pharyngeal neurons M2 and M3
CC (PubMed:14555955). EMPGVLRF-amide: Expressed in cholinergic pharyngeal
CC motoneurons M2 and M3 (PubMed:16187307). {ECO:0000269|PubMed:14555955,
CC ECO:0000269|PubMed:16187307, ECO:0000269|PubMed:23658528}.
CC -!- PTM: May be processed by convertase egl-3.
CC {ECO:0000305|PubMed:23658528}.
CC -!- MASS SPECTROMETRY: [SVPGVLRF-amide 1]: Mass=875; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11527423};
CC -!- SIMILARITY: Belongs to the FARP (FMRFamide related peptide) family.
CC {ECO:0000255}.
CC -!- CAUTION: Activity as ligand to G-protein coupled receptor npr-1 might
CC depend on a neomorphic gain-of-function sensitivity of the receptor
CC npr-1 associated with the Bristol N2 strains.
CC {ECO:0000303|PubMed:25804345}.
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DR EMBL; BX284606; CCD73111.1; -; Genomic_DNA.
DR RefSeq; NP_508514.2; NM_076113.5.
DR AlphaFoldDB; Q9N4V0; -.
DR BioGRID; 45531; 6.
DR STRING; 6239.Y48D7A.2.1; -.
DR PaxDb; Q9N4V0; -.
DR EnsemblMetazoa; Y48D7A.2.1; Y48D7A.2.1; WBGene00001461.
DR EnsemblMetazoa; Y48D7A.2.2; Y48D7A.2.2; WBGene00001461.
DR GeneID; 180587; -.
DR KEGG; cel:CELE_Y48D7A.2; -.
DR UCSC; Y48D7A.2.2; c. elegans.
DR CTD; 180587; -.
DR WormBase; Y48D7A.2; CE33736; WBGene00001461; flp-18.
DR eggNOG; ENOG502ST7F; Eukaryota.
DR GeneTree; ENSGT00970000196033; -.
DR HOGENOM; CLU_1321960_0_0_1; -.
DR InParanoid; Q9N4V0; -.
DR OMA; TEPIYEI; -.
DR OrthoDB; 1198420at2759; -.
DR PhylomeDB; Q9N4V0; -.
DR PRO; PR:Q9N4V0; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00001461; Expressed in larva and 4 other tissues.
DR GO; GO:0005576; C:extracellular region; IC:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IC:WormBase.
DR GO; GO:0031841; F:neuropeptide Y receptor binding; IC:WormBase.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:0006937; P:regulation of muscle contraction; IGI:UniProtKB.
DR GO; GO:0030431; P:sleep; IMP:UniProtKB.
DR InterPro; IPR002544; FMRFamid-related_peptide-like.
DR Pfam; PF01581; FARP; 8.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Neuropeptide; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..83
FT /id="PRO_0000009561"
FT PEPTIDE 86..93
FT /note="EMPGVLRF-amide"
FT /evidence="ECO:0000305"
FT /id="PRO_0000248055"
FT PROPEP 97..101
FT /evidence="ECO:0000305"
FT /id="PRO_0000248056"
FT PEPTIDE 104..111
FT /note="SVPGVLRF-amide 1"
FT /evidence="ECO:0000269|PubMed:11527423"
FT /id="PRO_0000009562"
FT PROPEP 115..119
FT /id="PRO_0000009563"
FT PEPTIDE 122..129
FT /note="SVPGVLRF-amide 2"
FT /evidence="ECO:0000269|PubMed:11527423"
FT /id="PRO_0000009564"
FT PROPEP 133..137
FT /evidence="ECO:0000305"
FT /id="PRO_0000009565"
FT PEPTIDE 140..147
FT /note="EIPGVLRF-amide"
FT /id="PRO_0000248057"
FT PROPEP 151..158
FT /evidence="ECO:0000305"
FT /id="PRO_0000248058"
FT PEPTIDE 161..169
FT /note="SEVPGVLRF-amide"
FT /id="PRO_0000248059"
FT PEPTIDE 173..180
FT /note="DVPGVLRF-amide"
FT /evidence="ECO:0000305"
FT /id="PRO_0000248060"
FT PROPEP 184..195
FT /evidence="ECO:0000305"
FT /id="PRO_0000248061"
FT PEPTIDE 198..205
FT /note="SVPGVLRF-amide 3"
FT /evidence="ECO:0000269|PubMed:11527423"
FT /id="PRO_0000009566"
FT MOD_RES 93
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
FT MOD_RES 111
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
FT MOD_RES 129
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
FT MOD_RES 147
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
FT MOD_RES 169
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
FT MOD_RES 180
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
FT MOD_RES 205
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:11527423"
SQ SEQUENCE 208 AA; 23809 MW; 19875F173E25008B CRC64;
MQRWSGVLLI SLCCLLRGAL AYTEPIYEIV EEDIPAEDIE VTRTNEKQDG RVFSKRDFDG
AMPGVLRFGK RGGVWEKRES SVQKKEMPGV LRFGKRAYFD EKKSVPGVLR FGKRSYFDEK
KSVPGVLRFG KRDVPMDKRE IPGVLRFGKR DYMADSFDKR SEVPGVLRFG KRDVPGVLRF
GKRSDLEEHY AGVLLKKSVP GVLRFGRK
