ID PYY_HUMAN Reviewed; 97 AA. AC P10082; Q5U5Q6; Q6FGH8; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 02-SEP-2026, entry version 210. DE RecName: Full=Peptide YY {ECO:0000303|PubMed:2587421}; DE Short=PYY {ECO:0000303|PubMed:2587421}; DE AltName: Full=PYY-I {ECO:0000250|UniProtKB:Q9TR93}; DE AltName: Full=Peptide tyrosine tyrosine; DE Contains: DE RecName: Full=Peptide YY(3-36) {ECO:0000303|PubMed:2587421}; DE AltName: Full=PYY-II {ECO:0000250|UniProtKB:Q9TR93}; DE Flags: Precursor; GN Name=PYY; 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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP GLY-37 AND ARG-72. RC TISSUE=Colon mucosa; RX PubMed=8318545; DOI=10.1016/0167-4781(93)90136-2; RA Kohri K., Nata K., Yonekura H., Nagai A., Konno K., Okamoto H.; RT "Cloning and structural determination of human peptide YY cDNA and gene."; RL Biochim. Biophys. Acta 1173:345-349(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-37. RA Herzog H.; RT "Genomic organisation and localisation of the gene for the human peptide RT YY."; RL Submitted (NOV-1993) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS GLY-37 AND RP ARG-72. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-37 AND RP ARG-72. 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 PROTEIN SEQUENCE OF 29-64, AMIDATION AT TYR-64, SYNTHESIS OF 29-64, AND RP VARIANT GLY-37. RX PubMed=3202875; DOI=10.1016/s0006-291x(88)80308-5; RA Tatemoto K., Nakano I., Makk G., Angwin P., Mann M., Schilling J., RA Go V.L.W.; RT "Isolation and primary structure of human peptide YY."; RL Biochem. Biophys. Res. Commun. 157:713-717(1988). RN [7] RP PROTEIN SEQUENCE OF 29-64, AMIDATION AT TYR-64, AND VARIANT GLY-37. RX PubMed=2587421; DOI=10.1016/0196-9781(89)90116-2; RA Eberlein G.A., Eysselein V.E., Schaeffer M., Layer P., Grandt D., RA Goebell H., Niebel W., Davis M., Lee T.D., Shively J.E., Reeve J.R. Jr.; RT "A new molecular form of PYY: structural characterization of human PYY(3- RT 36) and PYY(1-36)."; RL Peptides 10:797-803(1989). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=3840109; DOI=10.1016/0016-5085(85)90211-2; RA Adrian T.E., Ferri G.L., Bacarese-Hamilton A.J., Fuessl H.S., Polak J.M., RA Bloom S.R.; RT "Human distribution and release of a putative new gut hormone, peptide RT YY."; RL Gastroenterology 89:1070-1077(1985). RN [9] RP FUNCTION. RX PubMed=1317848; DOI=10.1016/s0021-9258(19)49854-2; RA Larhammar D., Blomqvist A.G., Yee F., Jazin E.E., Yoo H., Wahlestedt C.R.; RT "Cloning and functional expression of a human neuropeptide Y/peptide YY RT receptor of the Y1 type."; RL J. Biol. Chem. 267:10935-10938(1992). RN [10] RP FUNCTION. RX PubMed=7592910; DOI=10.1074/jbc.270.45.26758; RA Gerald C., Walker M.W., Vaysse P.J.-J., He C., Branchek T.A., RA Weinshank R.L.; RT "Expression cloning and pharmacological characterization of a human RT hippocampal neuropeptide Y/peptide YY Y2 receptor subtype."; RL J. Biol. Chem. 270:26758-26761(1995). RN [11] RP FUNCTION (PEPTIDE YY(3-36)). RX PubMed=12167864; DOI=10.1038/nature00887; RA Batterham R.L., Cowley M.A., Small C.J., Herzog H., Cohen M.A., Dakin C.L., RA Wren A.M., Brynes A.E., Low M.J., Ghatei M.A., Cone R.D., Bloom S.R.; RT "Gut hormone PYY(3-36) physiologically inhibits food intake."; RL Nature 418:650-654(2002). RN [12] 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 [13] RP STRUCTURE BY NMR OF 29-64. RX PubMed=16819834; DOI=10.1021/bi060359l; RA Nygaard R., Nielbo S., Schwartz T.W., Poulsen F.M.; RT "The PP-fold solution structure of human polypeptide YY and human PYY3-36 RT as determined by NMR."; RL Biochemistry 45:8350-8357(2006). RN [14] {ECO:0007744|PDB:7RT9} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 29-64. RX PubMed=35180645; DOI=10.1016/j.npep.2022.102231; RA Langley D.B., Schofield P., Jackson J., Herzog H., Christ D.; RT "Crystal structures of human neuropeptide Y (NPY) and peptide YY (PYY)."; RL Neuropeptides 92:102231-102231(2022). RN [15] {ECO:0007744|PDB:7YON} RP STRUCTURE BY ELECTRON MICROSCOPY (2.95 ANGSTROMS) OF 31-64 IN COMPLEX WITH RP NPY2R AND GNAI1, AND FUNCTION. RX PubMed=36525977; DOI=10.1016/j.str.2022.11.010; RA Kang H., Park C., Choi Y.K., Bae J., Kwon S., Kim J., Choi C., Seok C., RA Im W., Choi H.J.; RT "Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY RT signaling."; RL Structure 31:44-57.e6(2023). CC -!- FUNCTION: [Peptide YY]: Ligand for neuropeptide Y receptor type 1 CC (NPY1R) and neuropeptide Y receptor type 2 (NPY2R) (PubMed:1317848, CC PubMed:7592910, PubMed:36525977). Also binds NPY5R (By similarity). CC Receptor binding induces adenylate cyclase-inhibiting G protein-coupled CC receptor signaling, resulting in inhibition of cAMP production CC (PubMed:1317848, PubMed:7592910). Receptor activation by PYY also leads CC to an increase of intracellular Ca(2+) levels (PubMed:1317848, CC PubMed:36525977, PubMed:7592910). This gut peptide inhibits exocrine CC pancreatic secretion (By similarity). Involved in the regulation of CC colonic antisecretory tone, and colonic contractility (By similarity). CC {ECO:0000250|UniProtKB:P68005, ECO:0000250|UniProtKB:Q9EPS2, CC ECO:0000269|PubMed:1317848, ECO:0000269|PubMed:36525977, CC ECO:0000269|PubMed:7592910}. CC -!- FUNCTION: [Peptide YY(3-36)]: Is a NPY2R agonist involved in the down- CC regulation of appetite and food intake, probably acting on receptors CC located on proopiomelanocortin(POMC)-releasing and neuropeptide Y(NPY)- CC releasing neurons in the arcuate nucleus of hypothalamus CC (PubMed:12167864). In NPY-releasing neurons, NPY2R activation by PYY(3- CC 36) leads to membrane hyperpolarization and reduced release of the CC orexigenic neuropeptide NPY (By similarity). CC {ECO:0000250|UniProtKB:Q9EPS2, ECO:0000269|PubMed:12167864}. CC -!- INTERACTION: CC P10082; P25929: NPY1R; NbExp=2; IntAct=EBI-6655667, EBI-372227; CC P10082; P49146: NPY2R; NbExp=2; IntAct=EBI-6655667, EBI-6655721; CC -!- SUBCELLULAR LOCATION: [Peptide YY]: Secreted CC {ECO:0000269|PubMed:3840109}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Long; CC IsoId=P10082-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P10082-2; Sequence=VSP_005081; CC -!- PTM: The peptide YY form is cleaved at Pro-30 by the prolyl CC endopeptidase FAP (seprase) activity (in vitro) to generate peptide CC YY(3-36). {ECO:0000269|PubMed:21314817}. CC -!- SIMILARITY: Belongs to the NPY family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/46182/PYY"; 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; D13897; BAA02997.1; -; Genomic_DNA. DR EMBL; D13897; BAA02998.1; -; Genomic_DNA. DR EMBL; D13899; BAA03000.1; -; mRNA. DR EMBL; D13902; BAA03002.1; -; mRNA. DR EMBL; L25648; AAA36433.1; -; Genomic_DNA. DR EMBL; CR542129; CAG46926.1; -; mRNA. DR EMBL; AC007993; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC041057; AAH41057.1; -; mRNA. DR CCDS; CCDS32662.1; -. [P10082-1] DR CCDS; CCDS92333.1; -. [P10082-2] DR PIR; A31358; A31358. DR PIR; S33795; S33795. DR PIR; S34568; S34568. DR PIR; S34569; S34569. DR RefSeq; NP_001380957.1; NM_001394028.1. [P10082-1] DR RefSeq; NP_001380958.1; NM_001394029.1. [P10082-2] DR RefSeq; NP_004151.4; NM_004160.6. [P10082-1] DR PDB; 2DEZ; NMR; -; A=29-64. DR PDB; 2DF0; NMR; -; A=31-64. DR PDB; 2L60; NMR; -; A=32-64. DR PDB; 2NA5; NMR; -; A=31-64. DR PDB; 7RT9; X-ray; 1.90 A; Y/Z=29-64. DR PDB; 7YON; EM; 2.95 A; L=31-64. DR AlphaFoldDB; P10082; -. DR BMRB; P10082; -. DR EMDB; EMD-33984; -. DR SMR; P10082; -. DR BioGRID; 111670; 31. DR FunCoup; P10082; 512. DR IntAct; P10082; 9. DR MINT; P10082; -. DR NDEx; IQUERY-CP-PYY; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000353198; -. DR BioMuta; PYY; -. DR DMDM; 317373516; -. DR MassIVE; P10082; -. DR PaxDb; 9606-ENSP00000353198; -. DR PeptideAtlas; P10082; -. DR ProteomicsDB; 52563; -. [P10082-1] DR ProteomicsDB; 52564; -. [P10082-2] DR ABCD; P10082; 1 sequenced antibody. DR Antibodypedia; 3390; 464 antibodies from 32 providers. DR DNASU; 5697; -. DR Ensembl; ENST00000360085.6; ENSP00000353198.1; ENSG00000131096.12. [P10082-1] DR Ensembl; ENST00000592796.2; ENSP00000467310.1; ENSG00000131096.12. [P10082-2] DR Ensembl; ENST00000692052.1; ENSP00000509262.1; ENSG00000131096.12. [P10082-1] DR GeneID; 5697; -. DR KEGG; hsa:5697; -. DR MANE-Select; ENST00000692052.1; ENSP00000509262.1; NM_001394028.1; NP_001380957.1. DR UCSC; uc002ieq.4; human. [P10082-1] DR AGR; HGNC:9748; -. DR ClinPGx; PA34090; -. DR CTD; 5697; -. DR DisGeNET; 5697; -. DR GeneCards; PYY; -. DR HGNC; HGNC:9748; PYY. DR HPA; ENSG00000131096; Tissue enriched (intestine). DR MalaCards; PYY; -. DR MIM; 600781; gene. DR OpenTargets; ENSG00000131096; -. DR VEuPathDB; HostDB:ENSG00000131096; -. DR eggNOG; ENOG502S267; Eukaryota. DR GeneTree; ENSGT00940000160643; -. DR HOGENOM; CLU_162379_1_0_1; -. DR InParanoid; P10082; -. DR OMA; DSNRDQR; -. DR OrthoDB; 9852947at2759; -. DR PAN-GO; P10082; 5 GO annotations based on evolutionary models. DR PhylomeDB; P10082; -. DR PathwayCommons; P10082; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SignaLink; P10082; -. DR SIGNOR; P10082; -. DR Agora; ENSG00000131096; -. DR BioGRID-ORCS; 5697; 6 hits in 1140 CRISPR screens. DR ChiTaRS; PYY; human. DR EvolutionaryTrace; P10082; -. DR GeneWiki; Peptide_YY; -. DR GenomeRNAi; 5697; -. DR Pharos; P10082; Tbio. DR PRO; PR:P10082; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P10082; protein. DR Bgee; ENSG00000131096; Expressed in mucosa of sigmoid colon and 92 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:GO_Central. DR GO; GO:0005179; F:hormone 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:0048018; F:receptor ligand activity; IDA:UniProtKB. DR GO; GO:0007631; P:feeding behavior; IBA:GO_Central. DR GO; GO:0060575; P:intestinal epithelial cell differentiation; TAS:GO_Central. DR GO; GO:1903999; P:negative regulation of eating behavior; IDA:UniProtKB. DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central. 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:SF14; PEPTIDE YY-RELATED; 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 PDBsum; 2DEZ; -. DR PDBsum; 2DF0; -. DR PDBsum; 2L60; -. DR PDBsum; 2NA5; -. DR PDBsum; 7RT9; -. DR PDBsum; 7YON; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amidation; KW Cleavage on pair of basic residues; Direct protein sequencing; Hormone; KW Phosphoprotein; Proteomics identification; Reference proteome; Secreted; KW Signal. FT SIGNAL 1..28 FT /evidence="ECO:0000269|PubMed:2587421, FT ECO:0000269|PubMed:3202875" FT PEPTIDE 29..64 FT /note="Peptide YY" FT /id="PRO_0000025384" FT PEPTIDE 31..64 FT /note="Peptide YY(3-36)" FT /id="PRO_0000025385" FT PROPEP 68..97 FT /id="PRO_0000025386" FT REGION 65..97 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 82..97 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 30..31 FT /note="Cleavage; by FAP" FT /evidence="ECO:0000269|PubMed:21314817" FT MOD_RES 41 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P68005" FT MOD_RES 64 FT /note="Tyrosine amide" FT /evidence="ECO:0000269|PubMed:2587421, FT ECO:0000269|PubMed:3202875" FT VAR_SEQ 91..97 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8318545, ECO:0000303|Ref.3" FT /id="VSP_005081" FT VARIANT 37 FT /note="R -> G (in dbSNP:rs229969)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:2587421, ECO:0000269|PubMed:3202875, FT ECO:0000269|PubMed:8318545, ECO:0000269|Ref.2, FT ECO:0000269|Ref.3" FT /id="VAR_047407" FT VARIANT 72 FT /note="T -> R (in dbSNP:rs1058046)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:8318545, ECO:0000269|Ref.3" FT /id="VAR_006382" FT VARIANT 95 FT /note="D -> H (in dbSNP:rs465407)" FT /id="VAR_047408" FT HELIX 30..36 FT /evidence="ECO:0007829|PDB:7RT9" FT HELIX 42..61 FT /evidence="ECO:0007829|PDB:7RT9" SQ SEQUENCE 97 AA; 11145 MW; C166B73412E356B1 CRC64; MVFVRRPWPA LTTVLLALLV CLGALVDAYP IKPEAPREDA SPEELNRYYA SLRHYLNLVT RQRYGKRDGP DTLLSKTFFP DGEDRPVRSR SEGPDLW //