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   13-FEB-2019, entry version 180.
DE   RecName: Full=Pancreatic prohormone;
DE   AltName: Full=Pancreatic polypeptide;
DE            Short=PP;
DE   AltName: INN=Obinepitide;
DE   Contains:
DE     RecName: Full=Pancreatic hormone;
DE              Short=PH;
DE   Contains:
DE     RecName: Full=Pancreatic icosapeptide;
DE              Short=PI;
DE   Flags: Precursor;
GN   Name=PPY; Synonyms=PNP;
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] (ISOFORM 1), AND PROTEOLYTIC PROCESSING.
RC   TISSUE=Pancreas;
RX   PubMed=6373251;
RA   Boel E., Schwartz T.W., Norris K.E., Fiil N.P.;
RT   "A cDNA encoding a small common precursor for human pancreatic
RT   polypeptide 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;
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;
RA   Leiter A.B., Montminy M.R., Jamieson E., Goodman R.H.;
RT   "Exons of the human pancreatic polypeptide gene define functional
RT   domains 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.,
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   [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.,
RA   Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA   Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA   Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA   Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA   Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA   Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA   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
RT   the 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
RT   project: 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.,
RA   Nishigori T., 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
RT   immunocytochemical localization of the COOH-terminal fragment of the
RT   pancreatic polypeptide precursor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 81:708-712(1984).
RN   [9]
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
RT   are accompanied by changes in structure and membrane binding.";
RL   Biochemistry 44:9255-9264(2005).
CC   -!- FUNCTION: Pancreatic hormone is synthesized in pancreatic islets
CC       of Langerhans and acts as a regulator of pancreatic and
CC       gastrointestinal functions.
CC   -!- FUNCTION: The physiological role for the icosapeptide has not yet
CC       been elucidated.
CC   -!- SUBCELLULAR LOCATION: Secreted.
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         Note=No experimental confirmation available. Derived from EST
CC         data. {ECO:0000305};
CC   -!- PHARMACEUTICAL: Obinepitide is under clinical trial by 7TM Pharma
CC       to be used for the treatment of obesity. Obinepitide is derived
CC       from pancreatic hormone by having Gln-63.
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   UniGene; Hs.558368; -.
DR   UniGene; Hs.744427; -.
DR   PDB; 1TZ4; NMR; -; A=48-52.
DR   PDB; 1TZ5; NMR; -; A=30-47, A=53-65.
DR   PDBsum; 1TZ4; -.
DR   PDBsum; 1TZ5; -.
DR   ProteinModelPortal; P01298; -.
DR   SMR; P01298; -.
DR   BioGrid; 111531; 2.
DR   IntAct; P01298; 1.
DR   STRING; 9606.ENSP00000225992; -.
DR   SwissPalm; P01298; -.
DR   BioMuta; PPY; -.
DR   PaxDb; P01298; -.
DR   PeptideAtlas; P01298; -.
DR   PRIDE; P01298; -.
DR   ProteomicsDB; 51372; -.
DR   DNASU; 5539; -.
DR   Ensembl; ENST00000225992; ENSP00000225992; ENSG00000108849. [P01298-1]
DR   Ensembl; ENST00000591228; ENSP00000466009; ENSG00000108849. [P01298-1]
DR   GeneID; 5539; -.
DR   KEGG; hsa:5539; -.
DR   UCSC; uc002iep.4; human. [P01298-1]
DR   CTD; 5539; -.
DR   DisGeNET; 5539; -.
DR   EuPathDB; HostDB:ENSG00000108849.7; -.
DR   GeneCards; PPY; -.
DR   H-InvDB; HIX0039051; -.
DR   HGNC; HGNC:9327; PPY.
DR   HPA; CAB016735; -.
DR   HPA; HPA032122; -.
DR   MIM; 167780; gene.
DR   neXtProt; NX_P01298; -.
DR   OpenTargets; ENSG00000108849; -.
DR   PharmGKB; PA33690; -.
DR   eggNOG; ENOG410J7V9; Eukaryota.
DR   eggNOG; ENOG41115N2; LUCA.
DR   GeneTree; ENSGT00530000064295; -.
DR   HOGENOM; HOG000252942; -.
DR   InParanoid; P01298; -.
DR   KO; K05234; -.
DR   OrthoDB; 1586326at2759; -.
DR   PhylomeDB; P01298; -.
DR   TreeFam; TF332778; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SIGNOR; P01298; -.
DR   ChiTaRS; PPY; human.
DR   EvolutionaryTrace; P01298; -.
DR   GenomeRNAi; 5539; -.
DR   PRO; PR:P01298; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   Bgee; ENSG00000108849; Expressed in 46 organ(s), highest expression level in type B pancreatic cell.
DR   ExpressionAtlas; P01298; baseline and differential.
DR   Genevisible; P01298; HS.
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:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
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   InterPro; IPR015480; Pancreatic_hormone.
DR   InterPro; IPR001955; Pancreatic_hormone-like.
DR   InterPro; IPR020392; Pancreatic_hormone-like_CS.
DR   PANTHER; PTHR10533; PTHR10533; 1.
DR   PANTHER; PTHR10533:SF2; PTHR10533:SF2; 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; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Hormone; Pharmaceutical; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     29
FT   PEPTIDE      30     65       Pancreatic hormone.
FT                                /FTId=PRO_0000025365.
FT   PEPTIDE      69     88       Pancreatic icosapeptide.
FT                                /FTId=PRO_0000025366.
FT   PROPEP       89     95
FT                                /FTId=PRO_0000025367.
FT   MOD_RES      65     65       Tyrosine amide. {ECO:0000250}.
FT   VAR_SEQ      62     62       R -> RPRCVPQLGREIPAPGTLGPLHIPGHTLSPAPAPAP
FT                                SRPALGKTGHLCSTGLDQCALGKMVPTGRYETGGLAPGHSA
FT                                CPCCLFP (in isoform 2). {ECO:0000305}.
FT                                /FTId=VSP_057852.
FT   VARIANT      78     78       E -> G (in dbSNP:rs7215698).
FT                                /FTId=VAR_050615.
FT   CONFLICT     86     86       V -> I (in Ref. 4; AAA60161).
FT                                {ECO:0000305}.
FT   HELIX        43     47       {ECO:0000244|PDB:1TZ5}.
FT   HELIX        48     54       {ECO:0000244|PDB:1TZ4}.
FT   HELIX        55     60       {ECO:0000244|PDB:1TZ5}.
SQ   SEQUENCE   95 AA;  10445 MW;  44F0265092F9C4A0 CRC64;
     MAAARLCLSL LLLSTCVALL LQPLLGAQGA PLEPVYPGDN ATPEQMAQYA ADLRRYINML
     TRPRYGKRHK EDTLAFSEWG SPHAAVPREL SPLDL
//