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   24-JAN-2024, entry version 216.
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="https://atlasgeneticsoncology.org/gene/44438/NPY";
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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   PDB; 7X9A; EM; 3.20 A; P=29-64.
DR   PDB; 7X9B; EM; 3.40 A; P=29-64.
DR   PDB; 7YOO; EM; 3.11 A; L=29-64.
DR   PDBsum; 1QFA; -.
DR   PDBsum; 1RON; -.
DR   PDBsum; 7RTA; -.
DR   PDBsum; 7VGX; -.
DR   PDBsum; 7X9A; -.
DR   PDBsum; 7X9B; -.
DR   PDBsum; 7YOO; -.
DR   AlphaFoldDB; P01303; -.
DR   BMRB; P01303; -.
DR   EMDB; EMD-31979; -.
DR   EMDB; EMD-33069; -.
DR   EMDB; EMD-33070; -.
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; 9606-ENSP00000384364; -.
DR   PeptideAtlas; P01303; -.
DR   ProteomicsDB; 51373; -.
DR   ABCD; P01303; 1 sequenced antibody.
DR   Antibodypedia; 12195; 650 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   AGR; HGNC:7955; -.
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; 4180655at2759; -.
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 1143 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 146 other cell types or tissues.
DR   ExpressionAtlas; P01303; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:HGNC-UCL.
DR   GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0098992; C:neuronal dense core vesicle; ISS:UniProtKB.
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: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: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: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:0060575; P:intestinal epithelial cell differentiation; TAS:GO_Central.
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:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0099538; P:synaptic signaling via neuropeptide; IEA:Ensembl.
DR   CDD; cd00126; PAH; 1.
DR   Gene3D; 6.10.250.900; -; 1.
DR   InterPro; IPR001955; Pancreatic_hormone-like.
DR   InterPro; IPR020392; Pancreatic_hormone-like_CS.
DR   PANTHER; PTHR10533; NEUROPEPTIDE Y/PANCREATIC HORMONE/PEPTIDE YY; 1.
DR   PANTHER; PTHR10533:SF5; PRO-NEUROPEPTIDE Y; 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.
DR   Genevisible; P01303; HS.
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           42..61
FT                   /evidence="ECO:0007829|PDB:7RTA"
SQ   SEQUENCE   97 AA;  10851 MW;  832CF124321718F2 CRC64;
     MLGNKRLGLS GLTLALSLLV CLGALAEAYP SKPDNPGEDA PAEDMARYYS ALRHYINLIT
     RQRYGKRSSP ETLISDLLMR ESTENVPRTR LEDPAMW
//