PAHO_HUMAN
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 03-AUG-2022, entry version 199.
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; 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 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 hormone is synthesized in pancreatic islets of
CC Langerhans and acts as a regulator of pancreatic and gastrointestinal
CC functions.
CC -!- FUNCTION: The physiological role for the icosapeptide has not yet been
CC elucidated.
CC -!- INTERACTION:
CC P01298; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12121422, EBI-3867333;
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 -!- 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 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 PDB; 1TZ4; NMR; -; A=48-52.
DR PDB; 1TZ5; NMR; -; A=30-47, A=53-65.
DR PDBsum; 1TZ4; -.
DR PDBsum; 1TZ5; -.
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; P01298; -.
DR PeptideAtlas; P01298; -.
DR PRIDE; P01298; -.
DR ProteomicsDB; 51372; -.
DR ABCD; P01298; 1 sequenced antibody.
DR Antibodypedia; 29637; 419 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 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; LGFLEWG; -.
DR OrthoDB; 1586326at2759; -.
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; 287 hits in 1069 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 71 other tissues.
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; 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: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 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 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; Direct protein sequencing; Hormone;
KW Pharmaceutical; Reference proteome; Secreted; Signal.
FT SIGNAL 1..29
FT PEPTIDE 30..65
FT /note="Pancreatic hormone"
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..47
FT /evidence="ECO:0007829|PDB:1TZ5"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:1TZ4"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:1TZ5"
SQ SEQUENCE 95 AA; 10445 MW; 44F0265092F9C4A0 CRC64;
MAAARLCLSL LLLSTCVALL LQPLLGAQGA PLEPVYPGDN ATPEQMAQYA ADLRRYINML
TRPRYGKRHK EDTLAFSEWG SPHAAVPREL SPLDL
