ID   PAHO_HUMAN              Reviewed;          95 AA.
AC   P01298;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 208.
DE   RecName: Full=Pancreatic polypeptide prohormone {ECO:0000305};
DE            Short=PH;
DE   AltName: Full=Pancreatic polypeptide Y {ECO:0000312|HGNC:HGNC:9327};
DE   AltName: INN=Obinepitide {ECO:0000303|PubMed:24291217};
DE   Contains:
DE     RecName: Full=Pancreatic polypeptide {ECO:0000303|PubMed:6373251};
DE              Short=HPP {ECO:0000303|PubMed:828120};
DE              Short=PP {ECO:0000303|PubMed:6373251};
DE   Contains:
DE     RecName: Full=Pancreatic icosapeptide {ECO:0000303|PubMed:6373251};
DE              Short=PI;
DE   Flags: Precursor;
GN   Name=PPY {ECO:0000312|HGNC:HGNC:9327}; Synonyms=PNP;
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] (ISOFORM 1), AND PROTEOLYTIC PROCESSING.
RC   TISSUE=Pancreas;
RX   PubMed=6373251; DOI=10.1002/j.1460-2075.1984.tb01904.x;
RA   Boel E., Schwartz T.W., Norris K.E., Fiil N.P.;
RT   "A cDNA encoding a small common precursor for human pancreatic polypeptide
RT   and pancreatic icosapeptide.";
RL   EMBO J. 3:909-912(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Pancreatic tumor;
RX   PubMed=6094571; DOI=10.1016/s0021-9258(17)42659-7;
RA   Leiter A.B., Keutmann H.T., Goodman R.H.;
RT   "Structure of a precursor to human pancreatic polypeptide.";
RL   J. Biol. Chem. 259:14702-14705(1984).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX   PubMed=2997153; DOI=10.1016/s0021-9258(17)38830-0;
RA   Leiter A.B., Montminy M.R., Jamieson E., Goodman R.H.;
RT   "Exons of the human pancreatic polypeptide gene define functional domains
RT   of the precursor.";
RL   J. Biol. Chem. 260:13013-13017(1985).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Pancreas, and Spleen;
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-95 (ISOFORM 2).
RX   PubMed=14664712; DOI=10.1677/jme.0.0310519;
RA   Jin L., Wang H., Narita T., Kikuno R., Ohara O., Shihara N., Nishigori T.,
RA   Horikawa Y., Takeda J.;
RT   "Expression profile of mRNAs from human pancreatic islet tumors.";
RL   J. Mol. Endocrinol. 31:519-528(2003).
RN   [8]
RP   PROTEIN SEQUENCE OF 69-88.
RX   PubMed=6366786; DOI=10.1073/pnas.81.3.708;
RA   Schwartz T.W., Hansen H.F., Haakanson R., Sundler F., Tager H.S.;
RT   "Human pancreatic icosapeptide: isolation, sequence, and immunocytochemical
RT   localization of the COOH-terminal fragment of the pancreatic polypeptide
RT   precursor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 81:708-712(1984).
RN   [9]
RP   SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=828120; DOI=10.1136/gut.17.12.940;
RA   Adrian T.E., Bloom S.R., Bryant M.G., Polak J.M., Heitz P.H., Barnes A.J.;
RT   "Distribution and release of human pancreatic polypeptide.";
RL   Gut 17:940-944(1976).
RN   [10]
RP   INDUCTION.
RX   PubMed=514078; DOI=10.1016/0026-0495(79)90129-x;
RA   Gingerich R.L., Hickson R.C., Hagberg J.M., Winder W.W.;
RT   "Effect of endurance exercise training on plasma pancreatic polypeptide
RT   concentration during exercise.";
RL   Metabolism 28:1179-1182(1979).
RN   [11]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Placenta;
RX   PubMed=7592911; DOI=10.1074/jbc.270.45.26762;
RA   Bard J.A., Walker M.W., Branchek T.A., Weinshank R.L.;
RT   "Cloning and functional expression of a human Y4 subtype receptor for
RT   pancreatic polypeptide, neuropeptide Y, and peptide YY.";
RL   J. Biol. Chem. 270:26762-26765(1995).
RN   [12]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=7493937; DOI=10.1074/jbc.270.49.29123;
RA   Lundell I., Blomqvist A.G., Berglund M.M., Schober D.A., Johnson D.,
RA   Statnick M.A., Gadski R.A., Gehlert D.R., Larhammar D.;
RT   "Cloning of a human receptor of the NPY receptor family with high affinity
RT   for pancreatic polypeptide and peptide YY.";
RL   J. Biol. Chem. 270:29123-29128(1995).
RN   [13]
RP   NOMENCLATURE, AND PHARMACEUTICAL.
RX   PubMed=24291217; DOI=10.1016/j.drudis.2013.10.025;
RA   Davenport R.J., Wright S.;
RT   "Treating obesity: is it all in the gut?";
RL   Drug Discov. Today 19:845-858(2014).
RN   [14]
RP   STRUCTURE BY NMR OF 30-54.
RX   PubMed=15966750; DOI=10.1021/bi0501232;
RA   Lerch M., Kamimori H., Folkers G., Aguilar M.-I., Beck-Sickinger A.G.,
RA   Zerbe O.;
RT   "Strongly altered receptor binding properties in PP and NPY chimeras are
RT   accompanied by changes in structure and membrane binding.";
RL   Biochemistry 44:9255-9264(2005).
CC   -!- FUNCTION: [Pancreatic polypeptide]: Hormone secreted by pancreatic
CC       cells that acts as a regulator of pancreatic and gastrointestinal
CC       functions probably by signaling through the G protein-coupled receptor
CC       NPY4R2. {ECO:0000269|PubMed:7493937, ECO:0000269|PubMed:7592911}.
CC   -!- INTERACTION:
CC       P01298; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12121422, EBI-3867333;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7493937,
CC       ECO:0000269|PubMed:7592911, ECO:0000269|PubMed:828120}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P01298-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P01298-2; Sequence=VSP_057852;
CC   -!- INDUCTION: Released in circulation upon food intake (PubMed:828120).
CC       Also up-regulated by exercise (PubMed:514078).
CC       {ECO:0000269|PubMed:514078, ECO:0000269|PubMed:828120}.
CC   -!- PHARMACEUTICAL: Obinepitide is under clinical trial by 7TM Pharma to be
CC       used for the treatment of obesity. Obinepitide is derived from
CC       pancreatic hormone residues 30 to 65 with a Gln at position 63.
CC       {ECO:0000303|PubMed:24291217}.
CC   -!- SIMILARITY: Belongs to the NPY family. {ECO:0000305}.
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DR   EMBL; X00491; CAA25161.1; -; mRNA.
DR   EMBL; M11726; AAA60156.1; -; Genomic_DNA.
DR   EMBL; M15788; AAA60161.1; -; mRNA.
DR   EMBL; AC007993; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC032225; AAH32225.1; -; mRNA.
DR   EMBL; BC040033; AAH40033.1; -; mRNA.
DR   EMBL; BP385720; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS11472.1; -. [P01298-1]
DR   PIR; A92498; PCHU.
DR   RefSeq; NP_002713.1; NM_002722.4. [P01298-1]
DR   PDB; 1TZ4; NMR; -; A=48-52.
DR   PDB; 1TZ5; NMR; -; A=30-47, A=53-65.
DR   PDB; 7X9C; EM; 3.00 A; P=30-65.
DR   PDBsum; 1TZ4; -.
DR   PDBsum; 1TZ5; -.
DR   PDBsum; 7X9C; -.
DR   AlphaFoldDB; P01298; -.
DR   SMR; P01298; -.
DR   BioGRID; 111531; 13.
DR   IntAct; P01298; 1.
DR   STRING; 9606.ENSP00000466009; -.
DR   SwissPalm; P01298; -.
DR   BioMuta; PPY; -.
DR   MassIVE; P01298; -.
DR   PaxDb; 9606-ENSP00000466009; -.
DR   PeptideAtlas; P01298; -.
DR   ProteomicsDB; 51372; -.
DR   ABCD; P01298; 1 sequenced antibody.
DR   Antibodypedia; 29637; 445 antibodies from 36 providers.
DR   DNASU; 5539; -.
DR   Ensembl; ENST00000225992.8; ENSP00000225992.3; ENSG00000108849.8. [P01298-1]
DR   Ensembl; ENST00000591228.4; ENSP00000466009.1; ENSG00000108849.8. [P01298-1]
DR   GeneID; 5539; -.
DR   KEGG; hsa:5539; -.
DR   MANE-Select; ENST00000225992.8; ENSP00000225992.3; NM_002722.5; NP_002713.1.
DR   UCSC; uc002iep.4; human. [P01298-1]
DR   AGR; HGNC:9327; -.
DR   CTD; 5539; -.
DR   DisGeNET; 5539; -.
DR   GeneCards; PPY; -.
DR   HGNC; HGNC:9327; PPY.
DR   HPA; ENSG00000108849; Tissue enriched (pancreas).
DR   MIM; 167780; gene.
DR   neXtProt; NX_P01298; -.
DR   OpenTargets; ENSG00000108849; -.
DR   PharmGKB; PA33690; -.
DR   VEuPathDB; HostDB:ENSG00000108849; -.
DR   eggNOG; ENOG502TD4B; Eukaryota.
DR   GeneTree; ENSGT00530000064295; -.
DR   InParanoid; P01298; -.
DR   OMA; MAATRRC; -.
DR   OrthoDB; 4638016at2759; -.
DR   PhylomeDB; P01298; -.
DR   TreeFam; TF332778; -.
DR   PathwayCommons; P01298; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P01298; -.
DR   SIGNOR; P01298; -.
DR   BioGRID-ORCS; 5539; 292 hits in 1147 CRISPR screens.
DR   ChiTaRS; PPY; human.
DR   EvolutionaryTrace; P01298; -.
DR   GenomeRNAi; 5539; -.
DR   Pharos; P01298; Tbio.
DR   PRO; PR:P01298; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P01298; Protein.
DR   Bgee; ENSG00000108849; Expressed in type B pancreatic cell and 72 other cell types or tissues.
DR   ExpressionAtlas; P01298; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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:0007631; P:feeding behavior; IBA:GO_Central.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   GO; GO:0009306; P:protein secretion; TAS:ProtInc.
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:SF2; PANCREATIC PROHORMONE; 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; P01298; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Direct protein sequencing; Hormone;
KW   Pharmaceutical; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..29
FT   PEPTIDE         30..65
FT                   /note="Pancreatic polypeptide"
FT                   /id="PRO_0000025365"
FT   PEPTIDE         69..88
FT                   /note="Pancreatic icosapeptide"
FT                   /id="PRO_0000025366"
FT   PROPEP          89..95
FT                   /id="PRO_0000025367"
FT   MOD_RES         65
FT                   /note="Tyrosine amide"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         62
FT                   /note="R -> RPRCVPQLGREIPAPGTLGPLHIPGHTLSPAPAPAPSRPALGKTGHL
FT                   CSTGLDQCALGKMVPTGRYETGGLAPGHSACPCCLFP (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_057852"
FT   VARIANT         78
FT                   /note="E -> G (in dbSNP:rs7215698)"
FT                   /id="VAR_050615"
FT   CONFLICT        86
FT                   /note="V -> I (in Ref. 4; AAA60161)"
FT                   /evidence="ECO:0000305"
FT   HELIX           43..60
FT                   /evidence="ECO:0007829|PDB:7X9C"
SQ   SEQUENCE   95 AA;  10445 MW;  44F0265092F9C4A0 CRC64;
     MAAARLCLSL LLLSTCVALL LQPLLGAQGA PLEPVYPGDN ATPEQMAQYA ADLRRYINML
     TRPRYGKRHK EDTLAFSEWG SPHAAVPREL SPLDL
//