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Pancreatic prohormone (Pancreatic polypeptide) (PP) (Obinepitide) [Cleaved into: Pancreatic hormone (PH); Pancreatic icosapeptide (PI)]

 PAHO_HUMAN              Reviewed;          95 AA.
P01298;
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
21-JUL-1986, sequence version 1.
12-SEP-2018, entry version 177.
RecName: Full=Pancreatic prohormone;
AltName: Full=Pancreatic polypeptide;
Short=PP;
AltName: INN=Obinepitide;
Contains:
RecName: Full=Pancreatic hormone;
Short=PH;
Contains:
RecName: Full=Pancreatic icosapeptide;
Short=PI;
Flags: Precursor;
Name=PPY; Synonyms=PNP;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEOLYTIC PROCESSING.
TISSUE=Pancreas;
PubMed=6373251;
Boel E., Schwartz T.W., Norris K.E., Fiil N.P.;
"A cDNA encoding a small common precursor for human pancreatic
polypeptide and pancreatic icosapeptide.";
EMBO J. 3:909-912(1984).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Pancreatic tumor;
PubMed=6094571;
Leiter A.B., Keutmann H.T., Goodman R.H.;
"Structure of a precursor to human pancreatic polypeptide.";
J. Biol. Chem. 259:14702-14705(1984).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
PubMed=2997153;
Leiter A.B., Montminy M.R., Jamieson E., Goodman R.H.;
"Exons of the human pancreatic polypeptide gene define functional
domains of the precursor.";
J. Biol. Chem. 260:13013-13017(1985).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=3753985; DOI=10.1172/JCI112357;
Takeuchi T., Gumucio D.L., Yamada T., Meisler M.H., Minth C.D.,
Dixon J.E., Eddy R.E., Shows T.B.;
"Genes encoding pancreatic polypeptide and neuropeptide Y are on human
chromosomes 17 and 7.";
J. Clin. Invest. 77:1038-1041(1986).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16625196; DOI=10.1038/nature04689;
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
"DNA sequence of human chromosome 17 and analysis of rearrangement in
the human lineage.";
Nature 440:1045-1049(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Pancreas, and Spleen;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-95 (ISOFORM 2).
PubMed=14664712; DOI=10.1677/jme.0.0310519;
Jin L., Wang H., Narita T., Kikuno R., Ohara O., Shihara N.,
Nishigori T., Horikawa Y., Takeda J.;
"Expression profile of mRNAs from human pancreatic islet tumors.";
J. Mol. Endocrinol. 31:519-528(2003).
[8]
PROTEIN SEQUENCE OF 69-88.
PubMed=6366786; DOI=10.1073/pnas.81.3.708;
Schwartz T.W., Hansen H.F., Haakanson R., Sundler F., Tager H.S.;
"Human pancreatic icosapeptide: isolation, sequence, and
immunocytochemical localization of the COOH-terminal fragment of the
pancreatic polypeptide precursor.";
Proc. Natl. Acad. Sci. U.S.A. 81:708-712(1984).
[9]
STRUCTURE BY NMR OF 30-54.
PubMed=15966750; DOI=10.1021/bi0501232;
Lerch M., Kamimori H., Folkers G., Aguilar M.-I., Beck-Sickinger A.G.,
Zerbe O.;
"Strongly altered receptor binding properties in PP and NPY chimeras
are accompanied by changes in structure and membrane binding.";
Biochemistry 44:9255-9264(2005).
-!- FUNCTION: Pancreatic hormone is synthesized in pancreatic islets
of Langerhans and acts as a regulator of pancreatic and
gastrointestinal functions.
-!- FUNCTION: The physiological role for the icosapeptide has not yet
been elucidated.
-!- SUBCELLULAR LOCATION: Secreted.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P01298-1; Sequence=Displayed;
Name=2;
IsoId=P01298-2; Sequence=VSP_057852;
Note=No experimental confirmation available. Derived from EST
data. {ECO:0000305};
-!- PHARMACEUTICAL: Obinepitide is under clinical trial by 7TM Pharma
to be used for the treatment of obesity. Obinepitide is derived
from pancreatic hormone by having Gln-63.
-!- SIMILARITY: Belongs to the NPY family. {ECO:0000305}.
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EMBL; X00491; CAA25161.1; -; mRNA.
EMBL; M11726; AAA60156.1; -; Genomic_DNA.
EMBL; M15788; AAA60161.1; -; mRNA.
EMBL; AC007993; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC032225; AAH32225.1; -; mRNA.
EMBL; BC040033; AAH40033.1; -; mRNA.
EMBL; BP385720; -; NOT_ANNOTATED_CDS; mRNA.
CCDS; CCDS11472.1; -. [P01298-1]
PIR; A92498; PCHU.
RefSeq; NP_002713.1; NM_002722.4. [P01298-1]
UniGene; Hs.558368; -.
UniGene; Hs.744427; -.
PDB; 1TZ4; NMR; -; A=48-52.
PDB; 1TZ5; NMR; -; A=30-47, A=53-65.
PDBsum; 1TZ4; -.
PDBsum; 1TZ5; -.
ProteinModelPortal; P01298; -.
SMR; P01298; -.
BioGrid; 111531; 2.
IntAct; P01298; 1.
STRING; 9606.ENSP00000225992; -.
SwissPalm; P01298; -.
BioMuta; PPY; -.
PaxDb; P01298; -.
PeptideAtlas; P01298; -.
PRIDE; P01298; -.
ProteomicsDB; 51372; -.
DNASU; 5539; -.
Ensembl; ENST00000225992; ENSP00000225992; ENSG00000108849. [P01298-1]
Ensembl; ENST00000591228; ENSP00000466009; ENSG00000108849. [P01298-1]
GeneID; 5539; -.
KEGG; hsa:5539; -.
UCSC; uc002iep.4; human. [P01298-1]
CTD; 5539; -.
DisGeNET; 5539; -.
EuPathDB; HostDB:ENSG00000108849.7; -.
GeneCards; PPY; -.
H-InvDB; HIX0039051; -.
HGNC; HGNC:9327; PPY.
HPA; CAB016735; -.
HPA; HPA032122; -.
MIM; 167780; gene.
neXtProt; NX_P01298; -.
OpenTargets; ENSG00000108849; -.
PharmGKB; PA33690; -.
eggNOG; ENOG410J7V9; Eukaryota.
eggNOG; ENOG41115N2; LUCA.
GeneTree; ENSGT00530000064295; -.
HOGENOM; HOG000252942; -.
InParanoid; P01298; -.
KO; K05234; -.
PhylomeDB; P01298; -.
TreeFam; TF332778; -.
Reactome; R-HSA-375276; Peptide ligand-binding receptors.
Reactome; R-HSA-418594; G alpha (i) signalling events.
SIGNOR; P01298; -.
ChiTaRS; PPY; human.
EvolutionaryTrace; P01298; -.
GenomeRNAi; 5539; -.
PRO; PR:P01298; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000108849; Expressed in 46 organ(s), highest expression level in type B pancreatic cell.
CleanEx; HS_PPY; -.
ExpressionAtlas; P01298; baseline and differential.
Genevisible; P01298; HS.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0001664; F:G-protein coupled receptor binding; IPI:GO_Central.
GO; GO:0005179; F:hormone activity; TAS:ProtInc.
GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central.
GO; GO:0007631; P:feeding behavior; IBA:GO_Central.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:Reactome.
GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
GO; GO:0009306; P:protein secretion; TAS:ProtInc.
GO; GO:0032098; P:regulation of appetite; IBA:GO_Central.
CDD; cd00126; PAH; 1.
InterPro; IPR015480; Pancreatic_hormone.
InterPro; IPR001955; Pancreatic_hormone-like.
InterPro; IPR020392; Pancreatic_hormone-like_CS.
PANTHER; PTHR10533; PTHR10533; 1.
PANTHER; PTHR10533:SF2; PTHR10533:SF2; 1.
Pfam; PF00159; Hormone_3; 1.
PRINTS; PR00278; PANCHORMONE.
ProDom; PD001267; Pancreatic_hormone-like; 1.
SMART; SM00309; PAH; 1.
PROSITE; PS00265; PANCREATIC_HORMONE_1; 1.
PROSITE; PS50276; PANCREATIC_HORMONE_2; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Amidation;
Cleavage on pair of basic residues; Complete proteome;
Direct protein sequencing; Hormone; Pharmaceutical; Polymorphism;
Reference proteome; Secreted; Signal.
SIGNAL 1 29
PEPTIDE 30 65 Pancreatic hormone.
/FTId=PRO_0000025365.
PEPTIDE 69 88 Pancreatic icosapeptide.
/FTId=PRO_0000025366.
PROPEP 89 95
/FTId=PRO_0000025367.
MOD_RES 65 65 Tyrosine amide. {ECO:0000250}.
VAR_SEQ 62 62 R -> RPRCVPQLGREIPAPGTLGPLHIPGHTLSPAPAPAP
SRPALGKTGHLCSTGLDQCALGKMVPTGRYETGGLAPGHSA
CPCCLFP (in isoform 2). {ECO:0000305}.
/FTId=VSP_057852.
VARIANT 78 78 E -> G (in dbSNP:rs7215698).
/FTId=VAR_050615.
CONFLICT 86 86 V -> I (in Ref. 4; AAA60161).
{ECO:0000305}.
HELIX 43 47 {ECO:0000244|PDB:1TZ5}.
HELIX 48 54 {ECO:0000244|PDB:1TZ4}.
HELIX 55 60 {ECO:0000244|PDB:1TZ5}.
SEQUENCE 95 AA; 10445 MW; 44F0265092F9C4A0 CRC64;
MAAARLCLSL LLLSTCVALL LQPLLGAQGA PLEPVYPGDN ATPEQMAQYA ADLRRYINML
TRPRYGKRHK EDTLAFSEWG SPHAAVPREL SPLDL


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