ID NPFF_HUMAN Reviewed; 113 AA. AC O15130; Q3SXL4; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 02-JUN-2021, entry version 158. DE RecName: Full=Pro-FMRFamide-related neuropeptide FF; DE AltName: Full=FMRFamide-related peptides; DE Contains: DE RecName: Full=Neuropeptide SF; DE Short=NPSF; DE Contains: DE RecName: Full=Neuropeptide FF; DE Short=NPFF; DE Contains: DE RecName: Full=Neuropeptide AF; DE Short=NPAF; DE Flags: Precursor; GN Name=NPFF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=9224703; DOI=10.1016/s0014-5793(97)00557-7; RA Perry S.J., Yi-Kung Huang E., Cronk D., Bagust J., Sharma R., Walker R.J., RA Wilson S., Burke J.F.; RT "A human gene encoding morphine modulating peptides related to NPFF and RT FMRFamide."; RL FEBS Lett. 409:426-430(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION. RX PubMed=11587714; DOI=10.1016/s0028-3908(01)00107-1; RA Catarsi S., Babinski K., Seguela P.; RT "Selective modulation of heteromeric ASIC proton-gated channels by RT neuropeptide FF."; RL Neuropharmacology 41:592-600(2001). CC -!- FUNCTION: Morphine modulating peptides. Have wide-ranging physiologic CC effects, including the modulation of morphine-induced analgesia, CC elevation of arterial blood pressure, and increased somatostatin CC secretion from the pancreas. Neuropeptide FF potentiates and sensitizes CC ASIC1 and ASIC3 channels. {ECO:0000269|PubMed:11587714}. CC -!- INTERACTION: CC O15130-2; P48643: CCT5; NbExp=3; IntAct=EBI-25840002, EBI-355710; CC O15130-2; P07339: CTSD; NbExp=3; IntAct=EBI-25840002, EBI-2115097; CC O15130-2; P42858: HTT; NbExp=18; IntAct=EBI-25840002, EBI-466029; CC O15130-2; P13473-2: LAMP2; NbExp=3; IntAct=EBI-25840002, EBI-21591415; CC O15130-2; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-25840002, EBI-2623095; CC O15130-2; O76024: WFS1; NbExp=3; IntAct=EBI-25840002, EBI-720609; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15130-1; Sequence=Displayed; CC Name=2; CC IsoId=O15130-2; Sequence=VSP_056475; CC -!- SIMILARITY: Belongs to the FARP (FMRFamide related peptide) family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF005271; AAB64288.1; -; mRNA. DR EMBL; AC023509; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW96721.1; -; Genomic_DNA. DR EMBL; BC104234; AAI04235.1; -; mRNA. DR EMBL; BC104235; AAI04236.1; -; mRNA. DR CCDS; CCDS8862.1; -. [O15130-1] DR RefSeq; NP_001307225.1; NM_001320296.1. [O15130-2] DR RefSeq; NP_003708.1; NM_003717.3. [O15130-1] DR BioGRID; 114175; 2. DR IntAct; O15130; 7. DR STRING; 9606.ENSP00000267017; -. DR BioMuta; NPFF; -. DR PaxDb; O15130; -. DR PeptideAtlas; O15130; -. DR PRIDE; O15130; -. DR ProteomicsDB; 48466; -. [O15130-1] DR Antibodypedia; 15271; 135 antibodies. DR DNASU; 8620; -. DR Ensembl; ENST00000267017; ENSP00000267017; ENSG00000139574. [O15130-1] DR GeneID; 8620; -. DR KEGG; hsa:8620; -. DR UCSC; uc001sdw.1; human. [O15130-1] DR CTD; 8620; -. DR DisGeNET; 8620; -. DR GeneCards; NPFF; -. DR HGNC; HGNC:7901; NPFF. DR HPA; ENSG00000139574; Tissue enriched (epididymis). DR MIM; 604643; gene. DR neXtProt; NX_O15130; -. DR OpenTargets; ENSG00000139574; -. DR PharmGKB; PA31704; -. DR VEuPathDB; HostDB:ENSG00000139574.8; -. DR eggNOG; ENOG502S60B; Eukaryota. DR GeneTree; ENSGT00390000015021; -. DR HOGENOM; CLU_2102411_0_0_1; -. DR InParanoid; O15130; -. DR OMA; GEFWSLA; -. DR OrthoDB; 1435009at2759; -. DR PhylomeDB; O15130; -. DR TreeFam; TF330924; -. DR PathwayCommons; O15130; -. DR Reactome; R-HSA-389397; Orexin and neuropeptides FF and QRFP bind to their respective receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SIGNOR; O15130; -. DR BioGRID-ORCS; 8620; 6 hits in 986 CRISPR screens. DR GeneWiki; NPFF; -. DR GenomeRNAi; 8620; -. DR Pharos; O15130; Tbio. DR PRO; PR:O15130; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; O15130; protein. DR Bgee; ENSG00000139574; Expressed in testis and 81 other tissues. DR Genevisible; O15130; HS. DR GO; GO:0043679; C:axon terminus; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0043204; C:perikaryon; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0031982; C:vesicle; IEA:Ensembl. DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central. DR GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0060079; P:excitatory postsynaptic potential; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0032099; P:negative regulation of appetite; IEA:Ensembl. DR GO; GO:0010459; P:negative regulation of heart rate; IEA:Ensembl. DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0007218; P:neuropeptide signaling pathway; TAS:ProtInc. DR GO; GO:0045777; P:positive regulation of blood pressure; IEA:Ensembl. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:0003254; P:regulation of membrane depolarization; IEA:Ensembl. DR GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0043278; P:response to morphine; IEA:Ensembl. DR GO; GO:0070253; P:somatostatin secretion; IEA:Ensembl. DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl. DR GO; GO:0030103; P:vasopressin secretion; IEA:Ensembl. DR InterPro; IPR008065; NPFF. DR PANTHER; PTHR15044; PTHR15044; 1. DR Pfam; PF15085; NPFF; 1. DR PIRSF; PIRSF038092; FMRFamid-rel_pep_precur; 1. DR PRINTS; PR01682; FMRFAMIDEPEP. PE 1: Evidence at protein level; KW Alternative splicing; Amidation; Cleavage on pair of basic residues; KW Neuropeptide; Reference proteome; Secreted; Signal. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT PROPEP 21..65 FT /id="PRO_0000009898" FT PEPTIDE 66..76 FT /note="Neuropeptide SF" FT /id="PRO_0000009899" FT PEPTIDE 69..76 FT /note="Neuropeptide FF" FT /id="PRO_0000009900" FT PROPEP 79..92 FT /id="PRO_0000009901" FT PEPTIDE 93..110 FT /note="Neuropeptide AF" FT /id="PRO_0000009902" FT REGION 22..48 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 76 FT /note="Phenylalanine amide" FT /evidence="ECO:0000250" FT MOD_RES 110 FT /note="Phenylalanine amide" FT /evidence="ECO:0000250" FT VAR_SEQ 1..34 FT /note="MDSRQAAALLVLLLLIDGGCAEGPGGQQEDQLSA -> MVPQPPTTCPWKPV FT PSPCDLRVQGICPSSFPDTPLAQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056475" FT VARIANT 88 FT /note="W -> R (in dbSNP:rs35822762)" FT /id="VAR_049183" SQ SEQUENCE 113 AA; 12440 MW; 1E9D4ED2A69238E3 CRC64; MDSRQAAALL VLLLLIDGGC AEGPGGQQED QLSAEEDSEP LPPQDAQTSG SLLHYLLQAM ERPGRSQAFL FQPQRFGRNT QGSWRNEWLS PRAGEGLNSQ FWSLAAPQRF GKK //