ID NMU_HUMAN Reviewed; 174 AA. AC P48645; A0A250SH36; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 02-SEP-2026, entry version 181. DE RecName: Full=Neuromedin-U {ECO:0000305|PubMed:7619205}; DE Short=Prepro-NMU {ECO:0000303|PubMed:28874765}; DE Contains: DE RecName: Full=Neuromedin precursor-related peptide 36 {ECO:0000303|PubMed:28874765}; DE Short=NURP36 {ECO:0000303|PubMed:28874765}; DE Contains: DE RecName: Full=Neuromedin precursor-related peptide 33 {ECO:0000303|PubMed:28874765}; DE Short=NURP33 {ECO:0000303|PubMed:28874765}; DE Contains: DE RecName: Full=Neuromedin-U-25 {ECO:0000250|UniProtKB:P12760}; DE Short=NmU-25 {ECO:0000250|UniProtKB:P12760}; DE Flags: Precursor; GN Name=NMU {ECO:0000312|HGNC:HGNC:7859}; GN Synonyms=NMU1 {ECO:0000303|PubMed:7619205}; 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], AND TISSUE SPECIFICITY. RC TISSUE=Pituitary; RX PubMed=7619205; DOI=10.1677/jme.0.0140157; RA Austin C., Lo G., Nandha K.A., Meleagros L., Bloom S.R.; RT "Cloning and characterization of the cDNA encoding the human neuromedin U RT (NmU) precursor: NmU expression in the human gastrointestinal tract."; RL J. Mol. Endocrinol. 14:157-169(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=28874765; DOI=10.1038/s41598-017-10319-9; RA Mori K., Ida T., Fudetani M., Mori M., Kaiya H., Hino J., Nakahara K., RA Murakami N., Miyazato M., Kangawa K.; RT "Identification of neuromedin U precursor-related peptide and its possible RT role in the regulation of prolactin release."; RL Sci. Rep. 7:10468-10468(2017). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; 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 [6] RP FUNCTION. RX PubMed=15585845; DOI=10.4049/jimmunol.173.12.7230; RA Johnson E.N., Appelbaum E.R., Carpenter D.C., Cox R.F., Disa J., RA Foley J.J., Ghosh S.K., Naselsky D.P., Pullen M.A., Sarau H.M., RA Scheff S.R., Steplewski K.M., Zaks-Zilberman M., Aiyar N.; RT "Neuromedin U elicits cytokine release in murine Th2-type T cell clone RT D10.G4.1."; RL J. Immunol. 173:7230-7238(2004). RN [7] RP FUNCTION. RX PubMed=15331768; DOI=10.1124/mol.104.002337; RA Brighton P.J., Szekeres P.G., Wise A., Willars G.B.; RT "Signaling and ligand binding by recombinant neuromedin U receptors: RT evidence for dual coupling to Galphaq/11 and Galphai and an irreversible RT ligand-receptor interaction."; RL Mol. Pharmacol. 66:1544-1556(2004). RN [8] RP FUNCTION. RX PubMed=33857254; DOI=10.1371/journal.pone.0250232; RA Zhang W., Sakoda H., Nakazato Y., Islam M.N., Pattou F., Kerr-Conte J., RA Nakazato M.; RT "Neuromedin U uses Galphai2 and Galphao to suppress glucose-stimulated Ca2+ RT signaling and insulin secretion in pancreatic beta cells."; RL PLoS ONE 16:e0250232-e0250232(2021). RN [9] {ECO:0007744|PDB:7W53, ECO:0007744|PDB:7W55} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) OF 142-166 RP (NEUROMEDIN-U-25) IN COMPLEX WITH NMUR1; NMUR2; GNG2; GNB1 AND A CHIMERA OF RP GNAI1 AND GNAS, FUNCTION, AND REGION. RX PubMed=35440625; DOI=10.1038/s41467-022-29683-w; RA You C., Zhang Y., Xu P., Huang S., Yin W., Eric Xu H., Jiang Y.; RT "Structural insights into the peptide selectivity and activation of human RT neuromedin U receptors."; RL Nat. Commun. 13:2045-2045(2022). RN [10] {ECO:0007744|PDB:7XK8} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 142-166 RP (NEUROMEDIN-U-25) IN COMPLEX WITH NMUR2; GNAI1; GNB1 AND GNG2. RX PubMed=36575163; DOI=10.1038/s41467-022-34814-4; RA Zhao W., Zhang W., Wang M., Lu M., Chen S., Tang T., Schnapp G., Wagner H., RA Brennauer A., Yi C., Chu X., Han S., Wu B., Zhao Q.; RT "Ligand recognition and activation of neuromedin U receptor 2."; RL Nat. Commun. 13:7955-7955(2022). CC -!- FUNCTION: [Neuromedin-U-25]: Multifunctional neuropeptide that acts via CC two G protein-coupled receptors, NMUR1 and NMUR2 (PubMed:15331768, CC PubMed:35440625). Functionally, is involved in pleiotropic roles, CC including regulation of feeding, energy balance, blood pressure and CC smooth muscle contraction (By similarity). Additionally modulates CC hormone release and inflammatory responses in a tissue- and receptor- CC dependent manner (PubMed:15585845, PubMed:33857254). Mechanistically, CC binding to NMUR1 or NMUR2 results in coupling of receptors to Galpha CC proteins, namely GNAQ/Gaq or GNA11/Ga11 and GNAI1/Gai subunits CC (PubMed:15331768). GNAQ/Gaq or GNA11/Ga11 coupling leads to the CC activation of a phospholipase C (PLC), which hydrolyzes PIP2 CC (phosphatidylinositol 4,5-bisphosphate) into DAG (diacylglycerol) and CC IP3 (inositol trisphosphate), and subsequent intracellular calcium CC mobilization via IP3 receptors on the endoplasmic reticulum CC (PubMed:15331768). GNAI1/Gai coupling inhibits forskolin-stimulated CC cAMP accumulation (PubMed:15331768). In pancreatic beta cells, CC regulates insulin secretion through NMUR1 coupled to GNAI2 and GNAO1, CC resulting in reduced intracellular Ca2+ influx and cAMP levels CC (PubMed:33857254). Through NMUR1 in Th2-type T cells, enhances type 2 CC cytokine secretion and modulates inflammatory responses via activation CC of PLC-calcineurin-MEK and PI3K signaling pathways (PubMed:15585845). CC {ECO:0000250|UniProtKB:P12760, ECO:0000250|UniProtKB:P34964, CC ECO:0000269|PubMed:15331768, ECO:0000269|PubMed:15585845, CC ECO:0000269|PubMed:33857254, ECO:0000269|PubMed:35440625}. CC -!- FUNCTION: [Neuromedin precursor-related peptide 33]: Does not function CC as a ligand for either NMUR1 or NMUR2. Indirectly induces prolactin CC release although its potency is much lower than that of neuromedin CC precursor-related peptide 36. {ECO:0000250|UniProtKB:P12760}. CC -!- FUNCTION: [Neuromedin precursor-related peptide 36]: Does not function CC as a ligand for either NMUR1 or NMUR2. Indirectly induces prolactin CC release from lactotroph cells in the pituitary gland, probably via the CC hypothalamic dopaminergic system. {ECO:0000250|UniProtKB:P12760}. CC -!- INTERACTION: CC P48645; Q86V38: ATN1; NbExp=3; IntAct=EBI-10210351, EBI-11954292; CC P48645; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10210351, EBI-3867333; CC P48645; Q9UHG0: DCDC2; NbExp=3; IntAct=EBI-10210351, EBI-10303987; CC P48645; Q92876: KLK6; NbExp=3; IntAct=EBI-10210351, EBI-2432309; CC P48645; O76011: KRT34; NbExp=3; IntAct=EBI-10210351, EBI-1047093; CC P48645; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-10210351, EBI-11959885; CC P48645; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-10210351, EBI-11749135; CC P48645; Q9BYS1: KRTAP1-5; NbExp=3; IntAct=EBI-10210351, EBI-11741292; CC P48645; P60371: KRTAP10-6; NbExp=3; IntAct=EBI-10210351, EBI-12012928; CC P48645; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-10210351, EBI-11953334; CC P48645; Q9BYP8: KRTAP17-1; NbExp=5; IntAct=EBI-10210351, EBI-11988175; CC P48645; P26371: KRTAP5-9; NbExp=6; IntAct=EBI-10210351, EBI-3958099; CC P48645; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10210351, EBI-945833; CC P48645; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-10210351, EBI-22310682; CC P48645; P23219: PTGS1; NbExp=3; IntAct=EBI-10210351, EBI-6655935; CC -!- SUBCELLULAR LOCATION: [Neuromedin-U-25]: Secreted CC {ECO:0000250|UniProtKB:P12760}. CC -!- TISSUE SPECIFICITY: Expressed throughout the enteric nervous system CC with highest levels being found in the jejunum. Expressed in CC gastrointestinal tract (PubMed:7619205). {ECO:0000269|PubMed:7619205}. CC -!- SIMILARITY: Belongs to the NmU family. {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; X76029; CAA53619.1; -; mRNA. DR EMBL; BR001408; FAA01225.1; -; mRNA. DR EMBL; AC024243; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471057; EAX05471.1; -; Genomic_DNA. DR EMBL; BC012908; AAH12908.1; -; mRNA. DR CCDS; CCDS3501.1; -. DR PIR; I38063; I38063. DR RefSeq; NP_001278974.1; NM_001292045.2. DR RefSeq; NP_001278975.1; NM_001292046.2. DR RefSeq; NP_006672.1; NM_006681.4. DR PDB; 7W53; EM; 3.20 A; C=142-166. DR PDB; 7W55; EM; 2.80 A; C=142-166. DR PDB; 7XK8; EM; 3.30 A; P=142-166. DR AlphaFoldDB; P48645; -. DR EMDB; EMD-32313; -. DR EMDB; EMD-32314; -. DR EMDB; EMD-33247; -. DR SMR; P48645; -. DR BioGRID; 116082; 123. DR FunCoup; P48645; 372. DR IntAct; P48645; 87. DR STRING; 9606.ENSP00000264218; -. DR GlyGen; P48645; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P48645; -. DR PhosphoSitePlus; P48645; -. DR BioMuta; NMU; -. DR DMDM; 1346685; -. DR MassIVE; P48645; -. DR PaxDb; 9606-ENSP00000264218; -. DR PeptideAtlas; P48645; -. DR ProteomicsDB; 55919; -. DR Pumba; P48645; -. DR Antibodypedia; 12370; 171 antibodies from 29 providers. DR DNASU; 10874; -. DR Ensembl; ENST00000264218.7; ENSP00000264218.3; ENSG00000109255.12. DR Ensembl; ENST00000920357.1; ENSP00000590416.1; ENSG00000109255.12. DR Ensembl; ENST00000920363.1; ENSP00000590422.1; ENSG00000109255.12. DR Ensembl; ENST00000968007.1; ENSP00000638066.1; ENSG00000109255.12. DR GeneID; 10874; -. DR KEGG; hsa:10874; -. DR MANE-Select; ENST00000264218.7; ENSP00000264218.3; NM_006681.4; NP_006672.1. DR UCSC; uc003hbc.3; human. DR AGR; HGNC:7859; -. DR ClinPGx; PA31663; -. DR CTD; 10874; -. DR DisGeNET; 10874; -. DR GeneCards; NMU; -. DR HGNC; HGNC:7859; NMU. DR HPA; ENSG00000109255; Tissue enhanced (esophagus, skin, vagina). DR MIM; 605103; gene. DR OpenTargets; ENSG00000109255; -. DR VEuPathDB; HostDB:ENSG00000109255; -. DR eggNOG; ENOG502S36R; Eukaryota. DR GeneTree; ENSGT00510000048726; -. DR HOGENOM; CLU_090356_0_0_1; -. DR InParanoid; P48645; -. DR OMA; LWSEQEL; -. DR OrthoDB; 9879773at2759; -. DR PAN-GO; P48645; 5 GO annotations based on evolutionary models. DR PhylomeDB; P48645; -. DR PathwayCommons; P48645; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SignaLink; P48645; -. DR Agora; ENSG00000109255; -. DR BioGRID-ORCS; 10874; 9 hits in 1155 CRISPR screens. DR ChiTaRS; NMU; human. DR GenomeRNAi; 10874; -. DR Pharos; P48645; Tbio. DR PRO; PR:P48645; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P48645; protein. DR Bgee; ENSG00000109255; Expressed in tongue squamous epithelium and 141 other cell types or tissues. DR ExpressionAtlas; P48645; baseline and differential. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central. DR GO; GO:0042922; F:neuromedin U receptor binding; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0031839; F:type 1 neuromedin U receptor binding; IDA:UniProtKB. DR GO; GO:0031840; F:type 2 neuromedin U receptor binding; IDA:UniProtKB. DR GO; GO:0042755; P:eating behavior; IEA:Ensembl. DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0001696; P:gastric acid secretion; IEA:Ensembl. DR GO; GO:1903999; P:negative regulation of eating behavior; IEA:Ensembl. DR GO; GO:0060455; P:negative regulation of gastric acid secretion; IEA:Ensembl. DR GO; GO:0120061; P:negative regulation of gastric emptying; IEA:Ensembl. DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB. DR GO; GO:0009648; P:photoperiodism; IEA:Ensembl. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:0010460; P:positive regulation of heart rate; IEA:Ensembl. DR GO; GO:0031652; P:positive regulation of heat generation; IEA:Ensembl. DR GO; GO:1902722; P:positive regulation of prolactin secretion; IEA:Ensembl. DR GO; GO:1904058; P:positive regulation of sensory perception of pain; IEA:Ensembl. DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IBA:GO_Central. DR GO; GO:0120069; P:positive regulation of stomach fundus smooth muscle contraction; IEA:Ensembl. DR GO; GO:0050806; P:positive regulation of synaptic transmission; IBA:GO_Central. DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IEA:Ensembl. DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IEA:Ensembl. DR GO; GO:2000821; P:regulation of grooming behavior; IEA:Ensembl. DR GO; GO:0001659; P:temperature homeostasis; IEA:Ensembl. DR InterPro; IPR018070; Neuromedin-U_amidation-site. DR InterPro; IPR042384; NMU. DR InterPro; IPR008200; NMU_C. DR PANTHER; PTHR15390; NEUROMEDIN-U; 1. DR PANTHER; PTHR15390:SF0; NEUROMEDIN-U; 1. DR Pfam; PF02070; NMU; 1. DR SMART; SM00084; NMU; 1. DR PROSITE; PS00967; NMU; 1. DR PDBsum; 7W53; -. DR PDBsum; 7W55; -. DR PDBsum; 7XK8; -. PE 1: Evidence at protein level; KW 3D-structure; Amidation; Cleavage on pair of basic residues; Neuropeptide; KW Oxidation; Proteomics identification; Reference proteome; Secreted; Signal. FT SIGNAL 1..34 FT /evidence="ECO:0000255" FT PROPEP 35..103 FT /evidence="ECO:0000250|UniProtKB:P12760" FT /id="PRO_0000019772" FT PEPTIDE 104..139 FT /note="Neuromedin precursor-related peptide 36" FT /evidence="ECO:0000250|UniProtKB:P12760" FT /id="PRO_0000445765" FT PEPTIDE 104..136 FT /note="Neuromedin precursor-related peptide 33" FT /evidence="ECO:0000250|UniProtKB:P12760" FT /id="PRO_0000445766" FT PEPTIDE 142..166 FT /note="Neuromedin-U-25" FT /id="PRO_0000019773" FT PROPEP 170..174 FT /id="PRO_0000019774" FT REGION 159..166 FT /note="Involved in receptor binding" FT /evidence="ECO:0000269|PubMed:35440625" FT MOD_RES 139 FT /note="Methionine sulfoxide; partial" FT /evidence="ECO:0000250|UniProtKB:P12760" FT MOD_RES 166 FT /note="Asparagine amide" FT /evidence="ECO:0000250|UniProtKB:P12760" FT VARIANT 79 FT /note="E -> G (in dbSNP:rs35892915)" FT /id="VAR_053538" FT VARIANT 148 FT /note="F -> L (in dbSNP:rs12108463)" FT /id="VAR_053539" FT STRAND 153..156 FT /evidence="ECO:0007829|PDB:7XK8" SQ SEQUENCE 174 AA; 19741 MW; 8ABD8138769FA815 CRC64; MLRTESCRPR SPAGQVAAAS PLLLLLLLLA WCAGACRGAP ILPQGLQPEQ QLQLWNEIDD TCSSFLSIDS QPQASNALEE LCFMIMGMLP KPQEQDEKDN TKRFLFHYSK TQKLGKSNVV SSVVHPLLQL VPHLHERRMK RFRVDEEFQS PFASQSRGYF LFRPRNGRRS AGFI //