PYY (peptide YY)

2011-01-01   Maria Braoudaki , Fotini Tzortzatou-Stathopoulou 

Identity

HGNC
LOCATION
17q21.31
LOCUSID
ALIAS
PYY-I,PYY1

DNA/RNA

Atlas Image
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).

Proteins

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

Entity name
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 name
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 name
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 name
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 name
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 name
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

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 5697
MIM: 600781
HGNC: 9748
Ensembl: ENSG00000131096

Variants:

dbSNP: 5697
ClinVar: 5697
TCGA: ENSG00000131096
COSMIC: PYY

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000131096ENST00000360085P10082
ENSG00000131096ENST00000592796P10082

Expression (GTEx)

0
5
10
15
20
25
30
35

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
Peptide ligand-binding receptorsREACTOMER-HSA-375276
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (i) signalling eventsREACTOMER-HSA-418594

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA258NPY1RGenePathwayassociated
PA31741NPY2RGenePathwayassociated

References

Pubmed IDYearTitleCitations
179344482007PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans.117
229799962012Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis.87
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
230640142012A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin.77
162782592006Elevated peptide YY levels in adolescent girls with anorexia nervosa.61
213245682011The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).57
189872872009Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males.53
235194622013Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells.53
170879522006Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.39
197379112009Comparable effects of moderate intensity exercise on changes in anorectic gut hormone levels and energy intake to high intensity exercise.38

Citation

Maria Braoudaki ; Fotini Tzortzatou-Stathopoulou

PYY (peptide YY)

Atlas Genet Cytogenet Oncol Haematol. 2011-01-01

Online version: http://atlasgeneticsoncology.org/gene/46182/humanGenome