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PYY (peptide YY)

Written2011-01Maria Braoudaki, Fotini Tzortzatou-Stathopoulou
University Research Institute for the Study, Treatment of Childhood Genetic, Malignant Diseases, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece (MB); Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece (FTS)

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)PYY1
Other alias
HGNC (Hugo) PYY
LocusID (NCBI) 5697
Atlas_Id 46182
Location 17q21.31  [Link to chromosome band 17q21]
Location_base_pair Starts at 43952733 and ends at 44004469 bp from pter ( according to hg19-Feb_2009)  [Mapping PYY.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

 
  Human peptide YY (PYY). Adapted from Shih et al., 2009.
Description PYY gene is composed of 4 exons and 3 introns that span approximately 51732 bases (start 42030106 bp to end 42081837 bp from pter) oriented at the minus strand.
Transcription Two transcript variants (1048 bp and 1048 bp in length).

Protein

Description Size: 97 amino acids; 11046 Da.
Expression PYY is expressed predominantly in endocrine L-cells that line the distal small bowel and colon.
Localisation Extracellular, subcellular location: secreted granules. Co-localized with proglucagon products, glicentin and glucagon-like peptide-1 (GLP-1) and GLP-2. PYY is a gastrointestinal track-derived hormone synthesized by endocrine cells of terminal ileum and colon, involved in the regulation of food intake.
Function Enteroendocrine L-cells release two circulating forms of PYY in the distal gut: PYY1-36 and PYY3-36. The latter form is considered the predominant form in both fasted and fed states and is produced by the cleavage of the N-terminal Tyr-Pro residues from PYY1-36 by dipeptidyl-peptidase IV (DPPIV). PYY exerts its inhibitory actions via various Y receptors, including Y1 receptor-mediated epithelial responses and Y2 receptor-mediated neuronal effects. It inhibits food intake via NPY-2 receptors expressed by neurons of the arcuate nucleus of the hypothalamus. Generally, it is considered to act in the hypothalamus as a signal of satiety. Other inhibitory actions include slowing gastric emptying; increasing nutrient absorption, inducing intestinal anion and electrolytic secretion as well as slowing small intestine motility. In addition, it has been shown to decrease exocrine pancreatic secretion and act as an appetite suppressant in the fasting state at physiological concentrations.
Homology PPY or PNP or PP and NPY.

Mutations

Note Common polymorphisms: Arg72Thr, which has been associated with type-2 diabetes and in some cases with enhanced body mass. Other variants: Gln62Pro and Leu73Pro associated with body mass and obesity, respectively as well as A-23G,C888T and 3' UTR variant C+1134A. The latter has been related to enhanced body mass.

Implicated in

Note
  
Entity Colon cancer
Note Loss of PYY expression has been implicated in the development and progression to colon adenocarcinoma. PYY expression has been associated with elevated differentiation, whilst PYY treatment of colon cancers resulted in selected overexpression of enzymes frequently identified in the normal colonocytic phenotype. The colon cancer growth regulatory effects of PYY might be dose dependent.
  
  
Entity Pancreatic cancer and pancreatitis
Note PYY suppresses growth and levels of intracellular cyclic adenosine monophosphate (cAMP) in pancreatic adenocarcinoma. It is considered to have a therapeutic value for pancreatic cancer and pancreatitis, since it exerts its immune function by altering transcription factors vital for cell signaling pathways. In addition, administration of PYY has been shown to improve amylase and cytokine release in pancreatitis cases. It has also been suggested that PYY in combination with vitamin E exhibit a significantly increased inhibitory effect on pancreatic cancer in vitro.
  
  
Entity Breast cancer
Note PYY inhibits in vitro growth of breast cancer cells, however the exact mechanism of antitumor activity remains unknown. Previous studies have proposed that PYY reduces intracellular levels of cAMP in breast carcinoma cells. Moreover, it has been reported that combination of PYY with vitamin E results in a significant additive inhibition of breast carcinoma cells.
  
  
Entity Cancer cachexia
Note Cancer cachexia is generally characterized by decreased protein synthesis and loss in the small bowel. PYY has been shown to increase small bowel weight and protein content. However, the exact role of PYY on cancer cachexia has not yet been clarified.
  
  
Entity Body weight
Note PYY-36 plays a role in long-term body weight regulation, due to the negative correlation between PYY concentrations and adiposity markers in humans, such that PYY levels increase with weight loss and when leptin levels are low.
  
  
Entity Obesity and type II diabetes
Note Low endogenous PYY levels in obese individuals, have previously suggested that PYY deficiency may contribute to hyperinsulinemia and insulin resistance and predispose obesity and type II diabetes.
  

Bibliography

A PYY Q62P variant linked to human obesity.
Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Collier JM, Hebert S, Doelle H, Dent R, Pennacchio LA, McPherson R.
Hum Mol Genet. 2006 Feb 1;15(3):387-91. Epub 2005 Dec 20.
PMID 16368708
 
Low serum PYY is linked to insulin resistance in first-degree relatives of subjects with type 2 diabetes.
Boey D, Heilbronn L, Sainsbury A, Laybutt R, Kriketos A, Herzog H, Campbell LV.
Neuropeptides. 2006 Oct;40(5):317-24. Epub 2006 Oct 12.
PMID 17045646
 
Endocrinology: Basic and clinical principles.
Conn MP, Melmed S.
Humana Press. 1997.
 
Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses.
Cox HM, Tough IR, Woolston AM, Zhang L, Nguyen AD, Sainsbury A, Herzog H.
Cell Metab. 2010 Jun 9;11(6):532-42.
PMID 20519124
 
Endogenous PYY and NPY mediate tonic Y1- and Y2-mediated absorption in human and mouse colon.
Cox HM.
Nutrition. 2008 Sep;24(9):900-6. Epub 2008 Jul 26.
PMID 18662856
 
Peptide YY inhibits growth of human breast cancer in vitro and in vivo.
Grise KR, Rongione AJ, Laird EC, McFadden DW.
J Surg Res. 1999 Apr;82(2):151-5.
PMID 10090823
 
Peptide YY and vitamin E inhibit hormone-sensitive and -insensitive breast cancer cells.
Heisler T, Towfigh S, Simon N, McFadden DW.
J Surg Res. 2000b Jun 1;91(1):9-14.
PMID 10816343
 
Ghrelin and PYY in the regulation of energy balance and metabolism: lessons from mouse mutants.
Kirchner H, Tong J, Tschop MH, Pfluger PT.
Am J Physiol Endocrinol Metab. 2010 May;298(5):E909-19. Epub 2010 Feb 23. (REVIEW)
PMID 20179246
 
Effects of meals high in carbohydrate, protein, and fat on ghrelin and peptide YY secretion in prepubertal children.
Lomenick JP, Melguizo MS, Mitchell SL, Summar ML, Anderson JW.
J Clin Endocrinol Metab. 2009 Nov;94(11):4463-71. Epub 2009 Oct 9.
PMID 19820013
 
Serial plasma concentrations of PYY and ghrelin during chemotherapy in children with acute lymphoblastic leukemia.
Moschovi M, Trimis G, Vounatsou M, Katsibardi K, Margeli A, Dimitriadi F, Papassotiriou I, Chrousos G, Tzortzatou-Stathopoulou F.
J Pediatr Hematol Oncol. 2008 Oct;30(10):733-7.
PMID 19011469
 
Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.
Pfluger PT, Kampe J, Castaneda TR, Vahl T, D'Alessio DA, Kruthaupt T, Benoit SC, Cuntz U, Rochlitz HJ, Moehlig M, Pfeiffer AF, Koebnick C, Weickert MO, Otto B, Spranger J, Tschop MH.
J Clin Endocrinol Metab. 2007 Feb;92(2):583-8. Epub 2006 Nov 21.
PMID 17119001
 
Peptide YY (PYY) gene polymorphisms in the 3'-untranslated and proximal promoter regions regulate cellular gene expression and PYY secretion and metabolic syndrome traits in vivo.
Shih PA, Wang L, Chiron S, Wen G, Nievergelt C, Mahata M, Khandrika S, Rao F, Fung MM, Mahata SK, Hamilton BA, O'Connor DT.
J Clin Endocrinol Metab. 2009 Nov;94(11):4557-66. Epub 2009 Oct 9.
PMID 19820027
 
Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes.
Torekov SS, Larsen LH, Glumer C, Borch-Johnsen K, Jorgensen T, Holst JJ, Madsen OD, Hansen T, Pedersen O.
Diabetes. 2005 Jul;54(7):2261-5.
PMID 15983231
 
Peptide YY and cancer: current findings and potential clinical applications.
Tseng WW, Liu CD.
Peptides. 2002 Feb;23(2):389-95. (REVIEW)
PMID 11825654
 
PYY and the pancreas: inhibition of tumor growth and inflammation.
Vona-Davis L, McFadden DW.
Peptides. 2007 Feb;28(2):334-8. Epub 2006 Dec 27. (REVIEW)
PMID 17194501
 

Citation

This paper should be referenced as such :
Braoudaki, M ; Tzortzatou-Stathopoulou, F
PYY (peptide YY)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(8):674-676.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PYYID46182ch17q21.html


External links

Nomenclature
HGNC (Hugo)PYY   9748
Cards
AtlasPYYID46182ch17q21
Entrez_Gene (NCBI)PYY  5697  peptide YY
AliasesPYY-I; PYY1
GeneCards (Weizmann)PYY
Ensembl hg19 (Hinxton)ENSG00000131096 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000131096 [Gene_View]  chr17:43952733-44004469 [Contig_View]  PYY [Vega]
ICGC DataPortalENSG00000131096
TCGA cBioPortalPYY
AceView (NCBI)PYY
Genatlas (Paris)PYY
WikiGenes5697
SOURCE (Princeton)PYY
Genetics Home Reference (NIH)PYY
Genomic and cartography
GoldenPath hg38 (UCSC)PYY  -     chr17:43952733-44004469 -  17q21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PYY  -     17q21.31   [Description]    (hg19-Feb_2009)
EnsemblPYY - 17q21.31 [CytoView hg19]  PYY - 17q21.31 [CytoView hg38]
Mapping of homologs : NCBIPYY [Mapview hg19]  PYY [Mapview hg38]
OMIM600781   
Gene and transcription
Genbank (Entrez)AI654355 BC041057 CR542129 D13899 D13902
RefSeq transcript (Entrez)NM_004160
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PYY
Cluster EST : UnigeneHs.169249 [ NCBI ]
CGAP (NCI)Hs.169249
Alternative Splicing GalleryENSG00000131096
Gene ExpressionPYY [ NCBI-GEO ]   PYY [ EBI - ARRAY_EXPRESS ]   PYY [ SEEK ]   PYY [ MEM ]
Gene Expression Viewer (FireBrowse)PYY [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5697
GTEX Portal (Tissue expression)PYY
Human Protein AtlasENSG00000131096-PYY [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP10082   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP10082  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP10082
Splice isoforms : SwissVarP10082
PhosPhoSitePlusP10082
Domaine pattern : Prosite (Expaxy)PANCREATIC_HORMONE_1 (PS00265)    PANCREATIC_HORMONE_2 (PS50276)   
Domains : Interpro (EBI)Pancreatic_hormone-like    Pancreatic_hormone-like_CS   
Domain families : Pfam (Sanger)Hormone_3 (PF00159)   
Domain families : Pfam (NCBI)pfam00159   
Domain families : Smart (EMBL)PAH (SM00309)  
Domain structure : Prodom (Prabi Lyon)Pancreatic_hormone-like (PD001267)   
Conserved Domain (NCBI)PYY
DMDM Disease mutations5697
Blocks (Seattle)PYY
PDB (SRS)2DEZ    2DF0    2L60    2NA5   
PDB (PDBSum)2DEZ    2DF0    2L60    2NA5   
PDB (IMB)2DEZ    2DF0    2L60    2NA5   
PDB (RSDB)2DEZ    2DF0    2L60    2NA5   
Structural Biology KnowledgeBase2DEZ    2DF0    2L60    2NA5   
SCOP (Structural Classification of Proteins)2DEZ    2DF0    2L60    2NA5   
CATH (Classification of proteins structures)2DEZ    2DF0    2L60    2NA5   
SuperfamilyP10082
Human Protein Atlas [tissue]ENSG00000131096-PYY [tissue]
Peptide AtlasP10082
HPRD02869
IPIIPI00298252   IPI00219199   
Protein Interaction databases
DIP (DOE-UCLA)P10082
IntAct (EBI)P10082
FunCoupENSG00000131096
BioGRIDPYY
STRING (EMBL)PYY
ZODIACPYY
Ontologies - Pathways
QuickGOP10082
Ontology : AmiGOG-protein coupled receptor binding  hormone activity  neuropeptide hormone activity  protein binding  extracellular region  extracellular space  movement of cell or subcellular component  cytoskeleton organization  G-protein coupled receptor signaling pathway  neuropeptide signaling pathway  cell-cell signaling  digestion  feeding behavior  cell proliferation  regulation of appetite  eating behavior  
Ontology : EGO-EBIG-protein coupled receptor binding  hormone activity  neuropeptide hormone activity  protein binding  extracellular region  extracellular space  movement of cell or subcellular component  cytoskeleton organization  G-protein coupled receptor signaling pathway  neuropeptide signaling pathway  cell-cell signaling  digestion  feeding behavior  cell proliferation  regulation of appetite  eating behavior  
REACTOMEP10082 [protein]
REACTOME PathwaysR-HSA-418594 [pathway]   
NDEx NetworkPYY
Atlas of Cancer Signalling NetworkPYY
Wikipedia pathwaysPYY
Orthology - Evolution
OrthoDB5697
GeneTree (enSembl)ENSG00000131096
Phylogenetic Trees/Animal Genes : TreeFamPYY
HOVERGENP10082
HOGENOMP10082
Homologs : HomoloGenePYY
Homology/Alignments : Family Browser (UCSC)PYY
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPYY [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PYY
dbVarPYY
ClinVarPYY
1000_GenomesPYY 
Exome Variant ServerPYY
ExAC (Exome Aggregation Consortium)ENSG00000131096
GNOMAD BrowserENSG00000131096
Genetic variants : HAPMAP5697
Genomic Variants (DGV)PYY [DGVbeta]
DECIPHERPYY [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPYY 
Mutations
ICGC Data PortalPYY 
TCGA Data PortalPYY 
Broad Tumor PortalPYY
OASIS PortalPYY [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPYY  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPYY
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch PYY
DgiDB (Drug Gene Interaction Database)PYY
DoCM (Curated mutations)PYY (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PYY (select a term)
intoGenPYY
NCG5 (London)PYY
Cancer3DPYY(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600781   
Orphanet
MedgenPYY
Genetic Testing Registry PYY
NextProtP10082 [Medical]
TSGene5697
GENETestsPYY
Target ValidationPYY
Huge Navigator PYY [HugePedia]
snp3D : Map Gene to Disease5697
BioCentury BCIQPYY
ClinGenPYY
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5697
Chemical/Pharm GKB GenePA34090
Clinical trialPYY
Miscellaneous
canSAR (ICR)PYY (select the gene name)
Probes
Litterature
PubMed117 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePYY
EVEXPYY
GoPubMedPYY
iHOPPYY
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:31:46 CEST 2017

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