NPY_HUMAN
ID NPY_HUMAN Reviewed; 97 AA.
AC P01303;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Pro-neuropeptide Y;
DE Contains:
DE RecName: Full=Neuropeptide Y;
DE AltName: Full=Neuropeptide tyrosine;
DE Short=NPY;
DE Contains:
DE RecName: Full=C-flanking peptide of NPY;
DE Short=CPON;
DE Flags: Precursor;
GN Name=NPY;
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 AMIDATION AT TYR-64.
RX PubMed=6589611; DOI=10.1073/pnas.81.14.4577;
RA Minth C.D., Bloom S.R., Polak J.M., Dixon J.E.;
RT "Cloning, characterization, and DNA sequence of a human cDNA encoding
RT neuropeptide tyrosine.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4577-4581(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2427515; DOI=10.1016/s0021-9258(18)67189-3;
RA Minth C.D., Andrews P.C., Dixon J.E.;
RT "Characterization, sequence, and expression of the cloned human
RT neuropeptide Y gene.";
RL J. Biol. Chem. 261:11974-11979(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3753985; DOI=10.1172/jci112357;
RA Takeuchi T., Gumucio D.L., Yamada T., Meisler M.H., Minth C.D., Dixon J.E.,
RA Eddy R.E., Shows T.B.;
RT "Genes encoding pancreatic polypeptide and neuropeptide Y are on human
RT chromosomes 17 and 7.";
RL J. Clin. Invest. 77:1038-1041(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 IDENTIFICATION OF CPON.
RX PubMed=3839058; DOI=10.1016/0143-4179(85)90100-3;
RA Allen J.M., Polak J.M., Bloom S.R.;
RT "Presence of the predicted C-flanking peptide of neuropeptide Y (CPON) in
RT tissue extracts.";
RL Neuropeptides 6:95-100(1985).
RN [7]
RP CLEAVAGE BY FAP, AND CLEAVAGE SITE.
RX PubMed=21314817; DOI=10.1111/j.1742-4658.2011.08051.x;
RA Keane F.M., Nadvi N.A., Yao T.W., Gorrell M.D.;
RT "Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are
RT novel substrates of fibroblast activation protein-alpha.";
RL FEBS J. 278:1316-1332(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP STRUCTURE BY NMR OF 29-64.
RX PubMed=1425680; DOI=10.1111/j.1432-1033.1992.tb17346.x;
RA Darbon H., Bernassau J.-M., Deleuze C., Chenu J., Roussel A., Cambillau C.;
RT "Solution conformation of human neuropeptide Y by 1H nuclear magnetic
RT resonance and restrained molecular dynamics.";
RL Eur. J. Biochem. 209:765-771(1992).
RN [10]
RP STRUCTURE BY NMR OF 29-64.
RX PubMed=9008359; DOI=10.1007/bf00228141;
RA Monks S.A., Karagianis G., Howlett G.J., Norton R.S.;
RT "Solution structure of human neuropeptide Y.";
RL J. Biomol. NMR 8:379-390(1996).
RN [11]
RP STRUCTURE BY NMR OF 52-64.
RX PubMed=10561544; DOI=10.1016/s0167-4838(99)00214-9;
RA Barnham K.J., Catalfamo F., Pallaghy P.K., Howlett G.J., Norton R.S.;
RT "Helical structure and self-association in a 13 residue neuropeptide Y Y2
RT receptor agonist: relationship to biological activity.";
RL Biochim. Biophys. Acta 1435:127-137(1999).
CC -!- FUNCTION: NPY is implicated in the control of feeding and in secretion
CC of gonadotrophin-release hormone.
CC -!- INTERACTION:
CC P01303; F1D8P7: NR1H2; NbExp=3; IntAct=EBI-3905877, EBI-10177172;
CC P01303; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-3905877, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasmic vesicle, secretory vesicle,
CC neuronal dense core vesicle {ECO:0000250|UniProtKB:P07808}.
CC -!- TISSUE SPECIFICITY: One of the most abundant peptides in the nervous
CC system. Also found in some chromaffin cells of the adrenal medulla.
CC -!- PTM: The neuropeptide Y form is cleaved at Pro-30 by the prolyl
CC endopeptidase FAP (seprase) activity (in vitro).
CC {ECO:0000269|PubMed:21314817}.
CC -!- SIMILARITY: Belongs to the NPY family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Neuropeptide Y entry;
CC URL="https://en.wikipedia.org/wiki/Neuropeptide_Y";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NPYID44438ch7p15.html";
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DR EMBL; K01911; AAA59944.1; -; mRNA.
DR EMBL; M14298; AAA59945.1; -; Genomic_DNA.
DR EMBL; M14296; AAA59945.1; JOINED; Genomic_DNA.
DR EMBL; M14297; AAA59945.1; JOINED; Genomic_DNA.
DR EMBL; M15789; AAA59946.1; -; mRNA.
DR EMBL; AC004485; AAQ96843.1; -; Genomic_DNA.
DR EMBL; BC029497; AAH29497.1; -; mRNA.
DR CCDS; CCDS5387.1; -.
DR PIR; A25198; NYHUY.
DR RefSeq; NP_000896.1; NM_000905.3.
DR PDB; 1QFA; NMR; -; A=52-64.
DR PDB; 1RON; NMR; -; A=29-64.
DR PDB; 7RTA; X-ray; 2.60 A; N=29-64.
DR PDB; 7VGX; EM; 3.20 A; L=29-64.
DR PDBsum; 1QFA; -.
DR PDBsum; 1RON; -.
DR PDBsum; 7RTA; -.
DR PDBsum; 7VGX; -.
DR AlphaFoldDB; P01303; -.
DR BMRB; P01303; -.
DR SMR; P01303; -.
DR BioGRID; 110914; 8.
DR IntAct; P01303; 12.
DR MINT; P01303; -.
DR STRING; 9606.ENSP00000384364; -.
DR BindingDB; P01303; -.
DR DrugBank; DB02952; 2-aminoisobutyric acid.
DR DrugBank; DB03380; L-tyrosinamide.
DR DrugBank; DB00191; Phentermine.
DR iPTMnet; P01303; -.
DR PhosphoSitePlus; P01303; -.
DR BioMuta; NPY; -.
DR DMDM; 128117; -.
DR CPTAC; CPTAC-1287; -.
DR CPTAC; CPTAC-1288; -.
DR CPTAC; CPTAC-1289; -.
DR CPTAC; CPTAC-1290; -.
DR CPTAC; CPTAC-1291; -.
DR MassIVE; P01303; -.
DR PaxDb; P01303; -.
DR PeptideAtlas; P01303; -.
DR PRIDE; P01303; -.
DR ProteomicsDB; 51373; -.
DR ABCD; P01303; 1 sequenced antibody.
DR Antibodypedia; 12195; 602 antibodies from 40 providers.
DR DNASU; 4852; -.
DR Ensembl; ENST00000242152.7; ENSP00000242152.2; ENSG00000122585.8.
DR Ensembl; ENST00000405982.1; ENSP00000385282.1; ENSG00000122585.8.
DR Ensembl; ENST00000407573.5; ENSP00000384364.1; ENSG00000122585.8.
DR GeneID; 4852; -.
DR KEGG; hsa:4852; -.
DR MANE-Select; ENST00000242152.7; ENSP00000242152.2; NM_000905.4; NP_000896.1.
DR UCSC; uc003sww.3; human.
DR CTD; 4852; -.
DR DisGeNET; 4852; -.
DR GeneCards; NPY; -.
DR HGNC; HGNC:7955; NPY.
DR HPA; ENSG00000122585; Group enriched (adrenal gland, brain, prostate).
DR MIM; 162640; gene.
DR neXtProt; NX_P01303; -.
DR OpenTargets; ENSG00000122585; -.
DR PharmGKB; PA255; -.
DR VEuPathDB; HostDB:ENSG00000122585; -.
DR eggNOG; ENOG502S2BU; Eukaryota.
DR GeneTree; ENSGT00940000156475; -.
DR HOGENOM; CLU_162379_1_0_1; -.
DR InParanoid; P01303; -.
DR OMA; QGTMRLW; -.
DR OrthoDB; 1542445at2759; -.
DR PhylomeDB; P01303; -.
DR TreeFam; TF332778; -.
DR PathwayCommons; P01303; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR SignaLink; P01303; -.
DR SIGNOR; P01303; -.
DR BioGRID-ORCS; 4852; 4 hits in 1065 CRISPR screens.
DR ChiTaRS; NPY; human.
DR EvolutionaryTrace; P01303; -.
DR GeneWiki; Neuropeptide_Y; -.
DR GenomeRNAi; 4852; -.
DR Pharos; P01303; Tbio.
DR PRO; PR:P01303; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P01303; protein.
DR Bgee; ENSG00000122585; Expressed in ganglionic eminence and 145 other tissues.
DR ExpressionAtlas; P01303; baseline and differential.
DR Genevisible; P01303; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:HGNC-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0098992; C:neuronal dense core vesicle; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0005246; F:calcium channel regulator activity; TAS:ProtInc.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR GO; GO:0031841; F:neuropeptide Y receptor binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0008343; P:adult feeding behavior; ISS:HGNC-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0019732; P:antifungal humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0021954; P:central nervous system neuron development; IEP:DFLAT.
DR GO; GO:0021987; P:cerebral cortex development; IEP:DFLAT.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0007631; P:feeding behavior; IBA:GO_Central.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; TAS:GO_Central.
DR GO; GO:0042117; P:monocyte activation; IEA:Ensembl.
DR GO; GO:0002865; P:negative regulation of acute inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; IEP:DFLAT.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0032100; P:positive regulation of appetite; ISS:HGNC-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:0045964; P:positive regulation of dopamine metabolic process; IEA:Ensembl.
DR GO; GO:1904000; P:positive regulation of eating behavior; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:1904407; P:positive regulation of nitric oxide metabolic process; IEA:Ensembl.
DR GO; GO:0032903; P:regulation of nerve growth factor production; IEA:Ensembl.
DR GO; GO:0001878; P:response to yeast; IDA:UniProtKB.
DR GO; GO:0050909; P:sensory perception of taste; IEA:Ensembl.
DR GO; GO:0048572; P:short-day photoperiodism; IEA:Ensembl.
DR CDD; cd00126; PAH; 1.
DR InterPro; IPR001955; Pancreatic_hormone-like.
DR InterPro; IPR020392; Pancreatic_hormone-like_CS.
DR PANTHER; PTHR10533; PTHR10533; 1.
DR Pfam; PF00159; Hormone_3; 1.
DR PRINTS; PR00278; PANCHORMONE.
DR SMART; SM00309; PAH; 1.
DR PROSITE; PS00265; PANCREATIC_HORMONE_1; 1.
DR PROSITE; PS50276; PANCREATIC_HORMONE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Neuropeptide; Phosphoprotein; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:6589611"
FT PEPTIDE 29..64
FT /note="Neuropeptide Y"
FT /id="PRO_0000025321"
FT PEPTIDE 68..97
FT /note="C-flanking peptide of NPY"
FT /id="PRO_0000025322"
FT SITE 30..31
FT /note="Cleavage; by FAP"
FT /evidence="ECO:0000269|PubMed:21314817"
FT MOD_RES 64
FT /note="Tyrosine amide"
FT /evidence="ECO:0000269|PubMed:6589611"
FT MOD_RES 83
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 7
FT /note="L -> P (in dbSNP:rs16139)"
FT /id="VAR_014598"
FT VARIANT 22
FT /note="L -> M (in dbSNP:rs5571)"
FT /id="VAR_014599"
FT CONFLICT 53
FT /note="R -> G (in Ref. 2; AAA59945)"
FT /evidence="ECO:0000305"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:1RON"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1RON"
FT HELIX 53..63
FT /evidence="ECO:0007829|PDB:1QFA"
SQ SEQUENCE 97 AA; 10851 MW; 832CF124321718F2 CRC64;
MLGNKRLGLS GLTLALSLLV CLGALAEAYP SKPDNPGEDA PAEDMARYYS ALRHYINLIT
RQRYGKRSSP ETLISDLLMR ESTENVPRTR LEDPAMW
