PYY (peptide YY)

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

Identity

HGNC

PYY

LOCATION

17q21.31

LOCUSID

5697

ALIAS

PYY-I,PYY1

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).

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 ID	Last Year	Title	Authors
16368708	2006	A PYY Q62P variant linked to human obesity.	Ahituv N et al
17045646	2006	Low serum PYY is linked to insulin resistance in first-degree relatives of subjects with type 2 diabetes.	Boey D et al
20519124	2010	Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses.	Cox HM et al
18662856	2008	Endogenous PYY and NPY mediate tonic Y1- and Y2-mediated absorption in human and mouse colon.	Cox HM et al
10090823	1999	Peptide YY inhibits growth of human breast cancer in vitro and in vivo.	Grisé KR et al
10816343	2000	Peptide YY and vitamin E inhibit hormone-sensitive and -insensitive breast cancer cells.	Heisler T et al
20179246	2010	Ghrelin and PYY in the regulation of energy balance and metabolism: lessons from mouse mutants.	Kirchner H et al
19820013	2009	Effects of meals high in carbohydrate, protein, and fat on ghrelin and peptide YY secretion in prepubertal children.	Lomenick JP et al
19011469	2008	Serial plasma concentrations of PYY and ghrelin during chemotherapy in children with acute lymphoblastic leukemia.	Moschovi M et al
17119001	2007	Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.	Pfluger PT et al
19820027	2009	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 et al
15983231	2005	Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes.	Torekov SS et al
11825654	2002	Peptide YY and cancer: current findings and potential clinical applications.	Tseng WW et al
17194501	2007	PYY and the pancreas: inhibition of tumor growth and inflammation.	Vona-Davis L et al

Other Information

Locus ID:

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

Variants:

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

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000131096	ENST00000360085	P10082
ENSG00000131096	ENST00000592796	P10082

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Signal Transduction	REACTOME	R-HSA-162582
Signaling by GPCR	REACTOME	R-HSA-372790
GPCR ligand binding	REACTOME	R-HSA-500792
Class A/1 (Rhodopsin-like receptors)	REACTOME	R-HSA-373076
Peptide ligand-binding receptors	REACTOME	R-HSA-375276
GPCR downstream signaling	REACTOME	R-HSA-388396
G alpha (i) signalling events	REACTOME	R-HSA-418594

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA258	NPY1R	Gene	Pathway	associated
PA31741	NPY2R	Gene	Pathway	associated

References

Pubmed ID	Year	Title	Citations
17934448	2007	PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans.	117
22979996	2012	Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis.	87
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
23064014	2012	A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin.	77
16278259	2006	Elevated peptide YY levels in adolescent girls with anorexia nervosa.	61
21324568	2011	The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).	57
18987287	2009	Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males.	53
23519462	2013	Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells.	53
17087952	2006	Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.	39
19737911	2009	Comparable 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/pyy