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Protein

Pancreatic prohormone

Gene

PPY

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Pancreatic hormone is synthesized in pancreatic islets of Langerhans and acts as a regulator of pancreatic and gastrointestinal functions.
The physiological role for the icosapeptide has not yet been elucidated.

GO - Molecular functioni

  • G-protein coupled receptor binding Source: GO_Central
  • hormone activity Source: ProtInc
  • neuropeptide hormone activity Source: GO_Central
  • receptor binding Source: ProtInc

GO - Biological processi

  • cell-cell signaling Source: GO_Central
  • digestion Source: ProtInc
  • feeding behavior Source: GO_Central
  • mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
  • neuropeptide signaling pathway Source: GO_Central
  • positive regulation of defense response to virus by host Source: ParkinsonsUK-UCL
  • protein secretion Source: ProtInc
  • regulation of appetite Source: GO_Central
  • xenophagy Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418594. G alpha (i) signalling events.
SIGNORiP01298.

Names & Taxonomyi

Protein namesi
Recommended name:
Pancreatic prohormone
Alternative name(s):
Pancreatic polypeptide
Short name:
PP
INN: Obinepitide
Cleaved into the following 2 chains:
Pancreatic hormone
Short name:
PH
Gene namesi
Name:PPY
Synonyms:PNP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:9327. PPY.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

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.

Organism-specific databases

PharmGKBiPA33690.

Polymorphism and mutation databases

BioMutaiPPY.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929Add
BLAST
Peptidei30 – 6536Pancreatic hormonePRO_0000025365Add
BLAST
Peptidei69 – 8820Pancreatic icosapeptidePRO_0000025366Add
BLAST
Propeptidei89 – 957PRO_0000025367

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei65 – 651Tyrosine amideBy similarity

Keywords - PTMi

Amidation, Cleavage on pair of basic residues

Proteomic databases

PaxDbiP01298.
PRIDEiP01298.

PTM databases

SwissPalmiP01298.

Expressioni

Gene expression databases

BgeeiP01298.
CleanExiHS_PPY.
ExpressionAtlasiP01298. baseline and differential.
GenevisibleiP01298. HS.

Organism-specific databases

HPAiCAB016735.
HPA032122.

Interactioni

GO - Molecular functioni

  • G-protein coupled receptor binding Source: GO_Central
  • hormone activity Source: ProtInc
  • neuropeptide hormone activity Source: GO_Central
  • receptor binding Source: ProtInc

Protein-protein interaction databases

STRINGi9606.ENSP00000225992.

Structurei

Secondary structure

1
95
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 475Combined sources
Helixi48 – 525Combined sources
Helixi53 – 608Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TZ4NMR-A48-52[»]
1TZ5NMR-A30-47[»]
A53-65[»]
ProteinModelPortaliP01298.
SMRiP01298. Positions 30-65.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01298.

Family & Domainsi

Sequence similaritiesi

Belongs to the NPY family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J7V9. Eukaryota.
ENOG41115N2. LUCA.
GeneTreeiENSGT00530000064295.
HOGENOMiHOG000252942.
InParanoidiP01298.
KOiK05234.
PhylomeDBiP01298.
TreeFamiTF332778.

Family and domain databases

InterProiIPR015480. Pancreatic_hormone.
IPR001955. Pancreatic_hormone-like.
IPR020392. Pancreatic_hormone-like_CS.
[Graphical view]
PANTHERiPTHR10533. PTHR10533. 1 hit.
PTHR10533:SF2. PTHR10533:SF2. 1 hit.
PfamiPF00159. Hormone_3. 1 hit.
[Graphical view]
PRINTSiPR00278. PANCHORMONE.
ProDomiPD001267. Pancreatic_hormone-like. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00309. PAH. 1 hit.
[Graphical view]
PROSITEiPS00265. PANCREATIC_HORMONE_1. 1 hit.
PS50276. PANCREATIC_HORMONE_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01298-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAARLCLSL LLLSTCVALL LQPLLGAQGA PLEPVYPGDN ATPEQMAQYA
60 70 80 90
ADLRRYINML TRPRYGKRHK EDTLAFSEWG SPHAAVPREL SPLDL
Length:95
Mass (Da):10,445
Last modified:July 21, 1986 - v1
Checksum:i44F0265092F9C4A0
GO
Isoform 2 (identifier: P01298-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     62-62: R → RPRCVPQLGR...HSACPCCLFP

Note: No experimental confirmation available. Derived from EST data.Curated
Show »
Length:178
Mass (Da):18,786
Checksum:iF847D6246E7F608C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti86 – 861V → I in AAA60161 (PubMed:3753985).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781E → G.
Corresponds to variant rs7215698 [ dbSNP | Ensembl ].
VAR_050615

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei62 – 621R → RPRCVPQLGREIPAPGTLGP LHIPGHTLSPAPAPAPSRPA LGKTGHLCSTGLDQCALGKM VPTGRYETGGLAPGHSACPC CLFP in isoform 2. CuratedVSP_057852

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00491 mRNA. Translation: CAA25161.1.
M11726 Genomic DNA. Translation: AAA60156.1.
M15788 mRNA. Translation: AAA60161.1.
AC007993 Genomic DNA. No translation available.
BC032225 mRNA. Translation: AAH32225.1.
BC040033 mRNA. Translation: AAH40033.1.
BP385720 mRNA. No translation available.
CCDSiCCDS11472.1. [P01298-1]
PIRiA92498. PCHU.
RefSeqiNP_002713.1. NM_002722.4. [P01298-1]
UniGeneiHs.558368.
Hs.744427.

Genome annotation databases

EnsembliENST00000225992; ENSP00000225992; ENSG00000108849. [P01298-1]
ENST00000591228; ENSP00000466009; ENSG00000108849. [P01298-1]
GeneIDi5539.
KEGGihsa:5539.
UCSCiuc002iep.4. human. [P01298-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00491 mRNA. Translation: CAA25161.1.
M11726 Genomic DNA. Translation: AAA60156.1.
M15788 mRNA. Translation: AAA60161.1.
AC007993 Genomic DNA. No translation available.
BC032225 mRNA. Translation: AAH32225.1.
BC040033 mRNA. Translation: AAH40033.1.
BP385720 mRNA. No translation available.
CCDSiCCDS11472.1. [P01298-1]
PIRiA92498. PCHU.
RefSeqiNP_002713.1. NM_002722.4. [P01298-1]
UniGeneiHs.558368.
Hs.744427.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TZ4NMR-A48-52[»]
1TZ5NMR-A30-47[»]
A53-65[»]
ProteinModelPortaliP01298.
SMRiP01298. Positions 30-65.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000225992.

PTM databases

SwissPalmiP01298.

Polymorphism and mutation databases

BioMutaiPPY.

Proteomic databases

PaxDbiP01298.
PRIDEiP01298.

Protocols and materials databases

DNASUi5539.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000225992; ENSP00000225992; ENSG00000108849. [P01298-1]
ENST00000591228; ENSP00000466009; ENSG00000108849. [P01298-1]
GeneIDi5539.
KEGGihsa:5539.
UCSCiuc002iep.4. human. [P01298-1]

Organism-specific databases

CTDi5539.
GeneCardsiPPY.
H-InvDBHIX0039051.
HGNCiHGNC:9327. PPY.
HPAiCAB016735.
HPA032122.
MIMi167780. gene.
neXtProtiNX_P01298.
PharmGKBiPA33690.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J7V9. Eukaryota.
ENOG41115N2. LUCA.
GeneTreeiENSGT00530000064295.
HOGENOMiHOG000252942.
InParanoidiP01298.
KOiK05234.
PhylomeDBiP01298.
TreeFamiTF332778.

Enzyme and pathway databases

ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418594. G alpha (i) signalling events.
SIGNORiP01298.

Miscellaneous databases

ChiTaRSiPPY. human.
EvolutionaryTraceiP01298.
GenomeRNAii5539.
PROiP01298.
SOURCEiSearch...

Gene expression databases

BgeeiP01298.
CleanExiHS_PPY.
ExpressionAtlasiP01298. baseline and differential.
GenevisibleiP01298. HS.

Family and domain databases

InterProiIPR015480. Pancreatic_hormone.
IPR001955. Pancreatic_hormone-like.
IPR020392. Pancreatic_hormone-like_CS.
[Graphical view]
PANTHERiPTHR10533. PTHR10533. 1 hit.
PTHR10533:SF2. PTHR10533:SF2. 1 hit.
PfamiPF00159. Hormone_3. 1 hit.
[Graphical view]
PRINTSiPR00278. PANCHORMONE.
ProDomiPD001267. Pancreatic_hormone-like. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00309. PAH. 1 hit.
[Graphical view]
PROSITEiPS00265. PANCREATIC_HORMONE_1. 1 hit.
PS50276. PANCREATIC_HORMONE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A cDNA encoding a small common precursor for human pancreatic polypeptide and pancreatic icosapeptide."
    Boel E., Schwartz T.W., Norris K.E., Fiil N.P.
    EMBO J. 3:909-912(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEOLYTIC PROCESSING.
    Tissue: Pancreas.
  2. "Structure of a precursor to human pancreatic polypeptide."
    Leiter A.B., Keutmann H.T., Goodman R.H.
    J. Biol. Chem. 259:14702-14705(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Pancreatic tumor.
  3. "Exons of the human pancreatic polypeptide gene define functional domains of the precursor."
    Leiter A.B., Montminy M.R., Jamieson E., Goodman R.H.
    J. Biol. Chem. 260:13013-13017(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
  4. "Genes encoding pancreatic polypeptide and neuropeptide Y are on human chromosomes 17 and 7."
    Takeuchi T., Gumucio D.L., Yamada T., Meisler M.H., Minth C.D., Dixon J.E., Eddy R.E., Shows T.B.
    J. Clin. Invest. 77:1038-1041(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  5. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    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.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Pancreas and Spleen.
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-95 (ISOFORM 2).
  8. "Human pancreatic icosapeptide: isolation, sequence, and immunocytochemical localization of the COOH-terminal fragment of the pancreatic polypeptide precursor."
    Schwartz T.W., Hansen H.F., Haakanson R., Sundler F., Tager H.S.
    Proc. Natl. Acad. Sci. U.S.A. 81:708-712(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 69-88.
  9. "Strongly altered receptor binding properties in PP and NPY chimeras are accompanied by changes in structure and membrane binding."
    Lerch M., Kamimori H., Folkers G., Aguilar M.-I., Beck-Sickinger A.G., Zerbe O.
    Biochemistry 44:9255-9264(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 30-54.

Entry informationi

Entry nameiPAHO_HUMAN
AccessioniPrimary (citable) accession number: P01298
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 8, 2016
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.