Details for: PPY

Gene ID: 5539

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PPY

Ensembl ID: ENSG00000108849

Description: pancreatic polypeptide

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pancreatic PP cell CL0002275
    CSI 14.34
    rCSI 57.1%
    PRS 98.96
  • pancreatic D cell CL0000173
    CSI 13.64
    rCSI 13.42%
    PRS 99.23
  • pancreatic acinar cell CL0002064
    CSI 7.3
    rCSI 9.7%
    PRS 99.18
  • pancreatic A cell CL0000171
    CSI 6.57
    rCSI 6.88%
    PRS 99.25
  • type B pancreatic cell CL0000169
    CSI 5.31
    rCSI 11.76%
    PRS 99.02
  • pancreatic ductal cell CL0002079
    CSI 2.96
    rCSI 5.75%
    PRS 99.24
  • pancreatic epsilon cell CL0005019
    CSI 2.38
    rCSI 11.11%
    PRS 99.2
  • pancreatic stellate cell CL0002410
    CSI 1.81
    rCSI 10.5%
    PRS 99.25

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PPY](/details-gene/5539), or Pancreatic Polypeptide, encodes a 36-amino acid neuropeptide hormone primarily synthesized and secreted by endocrine cells of the pancreas. Functionally, it is involved in the regulation of metabolic processes, most notably [feeding behavior](/details-cell/GO:0007631) and satiety, by acting as a ligand for G protein-coupled receptors ([GO:0001664](/details-cell/GO:0001664)). Its expression is highly specific to the pancreas, with the highest significance observed in [pancreatic PP cell](/details-cell/CL0002275)s and [pancreatic D cell](/details-cell/CL0000173)s, establishing it as a key signaling molecule in the local pancreatic microenvironment and a systemic regulator of energy homeostasis. Early research elucidated its precursor structure and genomic location ([Link](https://doi.org/10.1016/s0021-9258(17)42659-7), [Link](https://doi.org/10.1172/jci112357)). ## Cellular Roles and Expression Landscape The expression profile of [PPY](/details-gene/5539) demonstrates profound specificity for pancreatic tissue. **Overall**, the gene shows its highest significance as a defining marker for [pancreatic PP cell](/details-cell/CL0002275)s (CSI: 14.34), also known as gamma cells, which are its primary source. It is also highly significant in other pancreatic endocrine and exocrine cells, including [pancreatic D cell](/details-cell/CL0000173)s (CSI: 13.64), [pancreatic acinar cell](/details-cell/CL0002064)s (CSI: 7.30), [pancreatic A cell](/details-cell/CL0000171)s (CSI: 6.57), and [type B pancreatic cell](/details-cell/CL0000169)s (CSI: 5.31). This co-expression within the islets of Langerhans suggests that beyond its systemic endocrine functions, [PPY](/details-gene/5539) may play a crucial paracrine role in modulating the secretion of other pancreatic hormones such as somatostatin, glucagon, and insulin. Its presence in acinar cells further suggests a potential role in regulating the secretion of digestive enzymes. The gene's clinical association with pancreatic polypeptide-secreting tumors is noted ([167780](https://omim.org/entry/167780)), and its expression in such tumors has been documented ([Link](https://doi.org/10.1677/jme.0.0310519)). ## Pathways and Molecular Function [PPY](/details-gene/5539) functions as a signaling hormone in the extracellular space ([GO:0005615](/details-cell/GO:0005615)). Its primary molecular function is as a neuropeptide hormone ([GO:0005184](/details-cell/GO:0005184)) that binds specifically to G protein-coupled receptors, particularly the Y4 receptor ([Link](https://doi.org/10.1074/jbc.270.45.26762)). This interaction initiates intracellular signaling cascades, primarily through [G alpha (i) signalling events](/details-cell/R-HSA-418594), which typically lead to the inhibition of adenylyl cyclase. This mechanism is a key component of the broader [Signaling by GPCR](/details-cell/R-HSA-372790) pathway. Biologically, these signaling events are integral to the regulation of [feeding behavior](/details-cell/GO:0007631), where PPY acts as an anorexigenic signal, reducing appetite and food intake after a meal. The release of PPY is known to be stimulated by food intake and exercise ([Link](https://doi.org/10.1016/0026-0495(79)90129-x)). ## Research Directions The highly localized expression of [PPY](/details-gene/5539) within the pancreatic islets and its established role in appetite regulation present clear avenues for further research, particularly in the context of metabolic diseases. **Proposed Hypotheses:** 1. **Intra-islet Paracrine Regulation:** The high significance of [PPY](/details-gene/5539) expression across multiple islet cell types suggests it functions as a local modulator. We hypothesize that PPY released from [pancreatic PP cell](/details-cell/CL0002275)s acts in a paracrine manner to inhibit insulin secretion from [type B pancreatic cell](/details-cell/CL0000169)s and glucagon secretion from [pancreatic A cell](/details-cell/CL0000171)s under specific metabolic conditions, thereby fine-tuning glucose homeostasis. 2. **Dysregulation in Type 2 Diabetes:** We hypothesize that in the progression of type 2 diabetes, the expression or secretion of PPY from [pancreatic PP cell](/details-cell/CL0002275)s is impaired. This loss of anorexigenic and paracrine signaling could contribute to both hyperphagia and the dysregulation of insulin and glucagon secretion characteristic of the disease. **Experimental Approach:** To test the hypothesis of intra-islet paracrine regulation (Hypothesis 1), one could utilize an ex vivo human pancreatic islet perifusion system. Islets from healthy donors would be cultured and subjected to glucose and other secretagogue challenges in the presence or absence of a specific Y4 receptor antagonist. Dynamic measurements of insulin, glucagon, and somatostatin secretion would be performed. A significant increase in insulin or glucagon release in the presence of the Y4 antagonist would demonstrate a tonic inhibitory role for endogenous PPY signaling within the islet. **Therapeutic Potential:** Given its function as a natural anorexigenic hormone, [PPY](/details-gene/5539) and its signaling pathway are attractive targets for the treatment of obesity ([Link](https://doi.org/10.1016/j.drudis.2013.10.025)). The therapeutic strategy would involve **activation** of the PPY pathway. The development of long-acting, stable peptide analogues of PPY that selectively agonize the Y4 receptor could serve as a potential anti-obesity therapy. This approach mimics the body's natural satiety signals to reduce food intake and promote weight loss.

Genular Protein ID: 1885099653

Symbol: PAHO_HUMAN

Name: N/A

UniProtKB Accession Codes:

P01298

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 6373251

Title: A cDNA encoding a small common precursor for human pancreatic polypeptide and pancreatic icosapeptide.

PubMed ID: 6373251

DOI: 10.1002/j.1460-2075.1984.tb01904.x

PubMed ID: 6094571

Title: Structure of a precursor to human pancreatic polypeptide.

PubMed ID: 6094571

DOI: 10.1016/s0021-9258(17)42659-7

PubMed ID: 2997153

Title: Exons of the human pancreatic polypeptide gene define functional domains of the precursor.

PubMed ID: 2997153

DOI: 10.1016/s0021-9258(17)38830-0

PubMed ID: 3753985

Title: Genes encoding pancreatic polypeptide and neuropeptide Y are on human chromosomes 17 and 7.

PubMed ID: 3753985

DOI: 10.1172/jci112357

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14664712

Title: Expression profile of mRNAs from human pancreatic islet tumors.

PubMed ID: 14664712

DOI: 10.1677/jme.0.0310519

PubMed ID: 6366786

Title: Human pancreatic icosapeptide: isolation, sequence, and immunocytochemical localization of the COOH-terminal fragment of the pancreatic polypeptide precursor.

PubMed ID: 6366786

DOI: 10.1073/pnas.81.3.708

PubMed ID: 828120

Title: Distribution and release of human pancreatic polypeptide.

PubMed ID: 828120

DOI: 10.1136/gut.17.12.940

PubMed ID: 514078

Title: Effect of endurance exercise training on plasma pancreatic polypeptide concentration during exercise.

PubMed ID: 514078

DOI: 10.1016/0026-0495(79)90129-x

PubMed ID: 7592911

Title: Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY.

PubMed ID: 7592911

DOI: 10.1074/jbc.270.45.26762

PubMed ID: 7493937

Title: Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY.

PubMed ID: 7493937

DOI: 10.1074/jbc.270.49.29123

PubMed ID: 24291217

Title: Treating obesity: is it all in the gut?

PubMed ID: 24291217

DOI: 10.1016/j.drudis.2013.10.025

PubMed ID: 15966750

Title: Strongly altered receptor binding properties in PP and NPY chimeras are accompanied by changes in structure and membrane binding.

PubMed ID: 15966750

DOI: 10.1021/bi0501232

Sequence Information:

  • Length: 95
  • Mass: 10445
  • Checksum: 44F0265092F9C4A0
  • Sequence:
    • MAAARLCLSL LLLSTCVALL LQPLLGAQGA PLEPVYPGDN ATPEQMAQYA ADLRRYINML 
TRPRYGKRHK EDTLAFSEWG SPHAAVPREL SPLDL