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   13-FEB-2019, entry version 187.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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;
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.,
RA   Dixon J.E., 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.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   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.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., 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
RT   project: 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)
RT   in 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
RT   YY are 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
RP   BY 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver 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.,
RA   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
RT   Y2 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
CC       secretion of gonadotrophin-release hormone.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: One of the most abundant peptides in the
CC       nervous system. Also found in some chromaffin cells of the adrenal
CC       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
CC       and 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   UniGene; Hs.1832; -.
DR   PDB; 1QFA; NMR; -; A=52-64.
DR   PDB; 1RON; NMR; -; A=29-64.
DR   PDBsum; 1QFA; -.
DR   PDBsum; 1RON; -.
DR   ProteinModelPortal; P01303; -.
DR   SMR; P01303; -.
DR   BioGrid; 110914; 7.
DR   IntAct; P01303; 10.
DR   MINT; P01303; -.
DR   STRING; 9606.ENSP00000242152; -.
DR   BindingDB; P01303; -.
DR   DrugBank; DB02952; Alpha-Aminoisobutyric Acid.
DR   DrugBank; DB03380; L-Tyrosinamide.
DR   iPTMnet; P01303; -.
DR   PhosphoSitePlus; P01303; -.
DR   BioMuta; NPY; -.
DR   DMDM; 128117; -.
DR   PaxDb; P01303; -.
DR   PeptideAtlas; P01303; -.
DR   PRIDE; P01303; -.
DR   ProteomicsDB; 51373; -.
DR   DNASU; 4852; -.
DR   Ensembl; ENST00000242152; ENSP00000242152; ENSG00000122585.
DR   Ensembl; ENST00000405982; ENSP00000385282; ENSG00000122585.
DR   Ensembl; ENST00000407573; ENSP00000384364; ENSG00000122585.
DR   GeneID; 4852; -.
DR   KEGG; hsa:4852; -.
DR   UCSC; uc003sww.3; human.
DR   CTD; 4852; -.
DR   DisGeNET; 4852; -.
DR   EuPathDB; HostDB:ENSG00000122585.7; -.
DR   GeneCards; NPY; -.
DR   HGNC; HGNC:7955; NPY.
DR   HPA; CAB016733; -.
DR   HPA; CAB034368; -.
DR   HPA; HPA036636; -.
DR   HPA; HPA044572; -.
DR   HPA; HPA056798; -.
DR   MIM; 162640; gene.
DR   neXtProt; NX_P01303; -.
DR   OpenTargets; ENSG00000122585; -.
DR   PharmGKB; PA255; -.
DR   eggNOG; ENOG410J0KC; Eukaryota.
DR   eggNOG; ENOG41128I2; LUCA.
DR   GeneTree; ENSGT00940000156475; -.
DR   HOGENOM; HOG000252942; -.
DR   HOVERGEN; HBG006485; -.
DR   InParanoid; P01303; -.
DR   KO; K05232; -.
DR   OMA; FEDPSMW; -.
DR   OrthoDB; 1542445at2759; -.
DR   PhylomeDB; P01303; -.
DR   TreeFam; TF332778; -.
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   SIGNOR; P01303; -.
DR   ChiTaRS; NPY; human.
DR   EvolutionaryTrace; P01303; -.
DR   GeneWiki; Neuropeptide_Y; -.
DR   GenomeRNAi; 4852; -.
DR   PMAP-CutDB; P01303; -.
DR   PRO; PR:P01303; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000122585; Expressed in 133 organ(s), highest expression level in prostate gland.
DR   Genevisible; P01303; HS.
DR   GO; GO:0005623; C:cell; TAS:ProtInc.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:HGNC.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
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: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.
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:0006816; P:calcium ion transport; TAS:ProtInc.
DR   GO; GO:0008283; P:cell population proliferation; TAS:ProtInc.
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; TAS:ProtInc.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
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: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.
DR   GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0001878; P:response to yeast; IDA:UniProtKB.
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   ProDom; PD001267; Pancreatic_hormone-like; 1.
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   Complete proteome; Neuropeptide; Phosphoprotein; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     28       {ECO:0000269|PubMed:6589611}.
FT   PEPTIDE      29     64       Neuropeptide Y.
FT                                /FTId=PRO_0000025321.
FT   PEPTIDE      68     97       C-flanking peptide of NPY.
FT                                /FTId=PRO_0000025322.
FT   SITE         30     31       Cleavage; by FAP.
FT                                {ECO:0000269|PubMed:21314817}.
FT   MOD_RES      64     64       Tyrosine amide.
FT                                {ECO:0000269|PubMed:6589611}.
FT   MOD_RES      83     83       Phosphothreonine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   VARIANT       7      7       L -> P (in dbSNP:rs16139).
FT                                /FTId=VAR_014598.
FT   VARIANT      22     22       L -> M (in dbSNP:rs5571).
FT                                /FTId=VAR_014599.
FT   CONFLICT     53     53       R -> G (in Ref. 2; AAA59945).
FT                                {ECO:0000305}.
FT   STRAND       31     33       {ECO:0000244|PDB:1RON}.
FT   HELIX        41     44       {ECO:0000244|PDB:1RON}.
FT   HELIX        53     63       {ECO:0000244|PDB:1QFA}.
SQ   SEQUENCE   97 AA;  10851 MW;  832CF124321718F2 CRC64;
     MLGNKRLGLS GLTLALSLLV CLGALAEAYP SKPDNPGEDA PAEDMARYYS ALRHYINLIT
     RQRYGKRSSP ETLISDLLMR ESTENVPRTR LEDPAMW
//