Details for: NPY

Gene ID: 4852

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: NPY

Ensembl ID: ENSG00000122585

Description: neuropeptide Y

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pancreatic D cell CL0000173
    CSI 19.07
    rCSI 18.75%
    PRS 99.6
  • precursor B cell CL0000817
    CSI 14.34
    rCSI 12.56%
    PRS 99.71
  • stromal cell CL0000499
    CSI 12.08
    rCSI 33.99%
    PRS 99.46
  • pancreatic A cell CL0000171
    CSI 11.14
    rCSI 11.67%
    PRS 99.55
  • forebrain radial glial cell CL0013000
    CSI 9.04
    rCSI 29%
    PRS 99.71
  • peripheral nervous system neuron CL2000032
    CSI 8.11
    rCSI 11.05%
    PRS 99.15
  • sst GABAergic cortical interneuron CL4023017
    CSI 7.93
    rCSI 10.23%
    PRS 98.82
  • pro-B cell CL0000826
    CSI 7.71
    rCSI 6.39%
    PRS 99.69
  • progenitor cell CL0011026
    CSI 7.03
    rCSI 14.96%
    PRS 98.88
  • type B pancreatic cell CL0000169
    CSI 4.71
    rCSI 10.43%
    PRS 99.36
  • luminal cell of prostate epithelium CL0002340
    CSI 4.7
    rCSI 25.27%
    PRS 99.57
  • fraction A pre-pro B cell CL0002045
    CSI 4.42
    rCSI 5.06%
    PRS 99.69
  • interneuron CL0000099
    CSI 4.36
    rCSI 8.76%
    PRS 99.13
  • glioblast CL0000030
    CSI 4.35
    rCSI 6.94%
    PRS 98.86
  • mesenchymal cell CL0008019
    CSI 3.96
    rCSI 10.06%
    PRS 99.54
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.86
    rCSI 4.46%
    PRS 98.98
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 3.26
    rCSI 9.62%
    PRS 99.68
  • neural progenitor cell CL0011020
    CSI 3.05
    rCSI 13.41%
    PRS 96.75
  • neural cell CL0002319
    CSI 2.89
    rCSI 10.9%
    PRS 97.58
  • glial cell CL0000125
    CSI 2.29
    rCSI 8.72%
    PRS 98.4
  • glutamatergic neuron CL0000679
    CSI 1.92
    rCSI 3.94%
    PRS 97.16
  • pancreatic PP cell CL0002275
    CSI 1.43
    rCSI 5.71%
    PRS 99.39

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.

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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)

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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 [NPY](/details-gene/4852) (neuropeptide Y) is a protein-coding gene located on human chromosome 7p15.3. It encodes a 36-amino acid neuropeptide that is widely distributed throughout the central and peripheral nervous systems. As a key signaling molecule, [NPY](/details-gene/4852) is involved in a diverse range of physiological processes, most notably the regulation of feeding behavior, energy balance, and blood pressure, as detailed in several foundational studies ([Link](https://doi.org/10.1073/pnas.81.14.4577), [Link](https://doi.org/10.1016/s0021-9258(18)67189-3)). Its function is mediated through binding to G protein-coupled receptors ([GO:0004930](https://www.ebi.ac.uk/QuickGO/term/GO:0004930)). Expression data indicates that [NPY](/details-gene/4852) is a highly significant marker in neuroendocrine cells, particularly [pancreatic D cell](/details-cell/CL0000173)s, as well as various neurons and early-stage B lymphocytes, suggesting a complex role spanning metabolism, neurotransmission, and potentially hematopoiesis. Clinically, it is associated with OMIM entry [162640](https://omim.org/entry/162640). ## Cellular Roles and Expression Landscape The expression profile of [NPY](/details-gene/4852) highlights its primary function as a neuroendocrine signaling peptide. **Overall**, its most significant expression is observed in cells of the pancreas and nervous system. It is a defining marker for [pancreatic D cell](/details-cell/CL0000173) (CSI: 19.07), [pancreatic A cell](/details-cell/CL0000171) (CSI: 11.14), and [type B pancreatic cell](/details-cell/CL0000169) (CSI: 4.71), underscoring its established role in the local regulation of islet hormone secretion and glucose homeostasis. Consistent with its name, [NPY](/details-gene/4852) shows high significance in neuronal populations, including [peripheral nervous system neuron](/details-cell/CL2000032)s (CSI: 8.11), [sst GABAergic cortical interneuron](/details-cell/CL4023017)s (CSI: 7.93), and developing neural cells such as [forebrain radial glial cell](/details-cell/CL0013000)s (CSI: 9.04). This pattern aligns with its function in chemical synaptic transmission ([GO:0007268](https://www.ebi.ac.uk/QuickGO/term/GO:0007268)) and neuronal development. Interestingly, [NPY](/details-gene/4852) also demonstrates high significance in the B lymphocyte lineage, specifically in [precursor B cell](/details-cell/CL0000817) (CSI: 14.34) and [pro-B cell](/details-cell/CL0000826)s (CSI: 7.71). This, combined with its high expression in [stromal cell](/details-cell/CL0000499)s (CSI: 12.08), which constitute the hematopoietic niche, suggests a potential, less-characterized role in B cell development or immune modulation. The broad expression in these distinct cell lineages—neuroendocrine, neuronal, and hematopoietic—points to [NPY](/details-gene/4852) as a pleiotropic signaling molecule with context-dependent functions. ## Pathways and Molecular Function The molecular functions of [NPY](/details-gene/4852) are centered on its role as a secreted signaling peptide that acts via G protein-coupled receptors. Functional annotations confirm its activity in the 'Neuropeptide signaling pathway' ([GO:0007218](https://www.ebi.ac.uk/QuickGO/term/GO:0007218)) and its binding affinity for neuropeptide Y receptors ([GO:0031841](https://www.ebi.ac.uk/QuickGO/term/GO:0031841)). This interaction primarily triggers 'G alpha (i) signalling events' ([R-HSA-418594](https://reactome.org/content/detail/R-HSA-418594)), which typically lead to the inhibition of adenylyl cyclase and a decrease in intracellular cAMP levels. The biological processes influenced by [NPY](/details-gene/4852) are diverse. Its best-characterized role is in the 'Positive regulation of appetite' ([GO:0032100](https://www.ebi.ac.uk/QuickGO/term/GO:0032100)) and 'Feeding behavior' ([GO:0007631](https://www.ebi.ac.uk/QuickGO/term/GO:0007631)). Additionally, it is implicated in the 'Regulation of blood pressure' ([GO:0008217](https://www.ebi.ac.uk/QuickGO/term/GO:0008217)) and central nervous system development ([GO:0021954](https://www.ebi.ac.uk/QuickGO/term/GO:0021954)). Emerging roles in immunity are suggested by its annotation to the 'Innate immune response' ([GO:0045087](https://www.ebi.ac.uk/QuickGO/term/GO:0045087)) and 'Antimicrobial humoral immune response' ([GO:0061844](https://www.ebi.ac.uk/QuickGO/term/GO:0061844)), which may be linked to its expression in early B cells or its function as an antimicrobial peptide. As a secreted protein, [NPY](/details-gene/4852) is localized to the 'Extracellular region' ([GO:0005576](https://www.ebi.ac.uk/QuickGO/term/GO:0005576)) and 'Neuronal dense core vesicle's ([GO:0098992](https://www.ebi.ac.uk/QuickGO/term/GO:0098992)) prior to release. ## Research Directions The well-established role of [NPY](/details-gene/4852) in neuroendocrine regulation contrasts with its less-understood significance in other cell types, providing fertile ground for new research. The high expression in early B-cell precursors is particularly intriguing. ### Proposed Hypotheses: 1. **Paracrine Regulation of Hematopoiesis:** Given its high significance in both [stromal cell](/details-cell/CL0000499)s and [precursor B cell](/details-cell/CL0000817)s within the bone marrow niche, we hypothesize that stromal-derived [NPY](/details-gene/4852) acts as a paracrine factor to regulate the proliferation, survival, or differentiation of B-lymphocyte progenitors. 2. **Coordination of Central and Pancreatic Metabolic Control:** We hypothesize that [NPY](/details-gene/4852) released from pancreatic islet cells ([pancreatic D cell](/details-cell/CL0000173)s) functions as a local metabolic sensor, fine-tuning the secretion of insulin and glucagon in a manner that complements its central, appetite-regulating effects in the hypothalamus. ### Key Experimental Approach: To test the hypothesis regarding its role in hematopoiesis (Hypothesis 1), an *in vitro* co-culture system could be employed. [NPY](/details-gene/4852) expression in primary human bone marrow [stromal cell](/details-cell/CL0000499)s could be knocked down using CRISPR-Cas9 or shRNA. These modified stromal cells would then be co-cultured with CD34+ hematopoietic stem and progenitor cells. The progression of B-cell development could be quantified over time using flow cytometry to measure the frequencies of distinct developmental stages (e.g., pro-B, pre-B cells). A significant reduction in the output of B-cell precursors from co-cultures with [NPY](/details-gene/4852)-deficient stroma would provide strong evidence for its role as a niche factor in B lymphopoiesis. ### Therapeutic Potential: As a secreted peptide signaling through cell-surface GPCRs, [NPY](/details-gene/4852) and its receptors are classical drug targets. Its potent orexigenic (appetite-stimulating) effects have made its pathway a long-standing target for therapies against obesity and metabolic syndrome, where receptor **inhibition** via antagonists would be the primary strategy. Conversely, receptor **activation** via agonists could hold potential for treating conditions involving wasting or cachexia. The major challenge for systemic therapies is the pleiotropic nature of [NPY](/details-gene/4852) signaling, with widespread effects on blood pressure, anxiety, and other CNS functions. Future therapeutic success will likely depend on the development of receptor subtype-specific modulators or targeted delivery systems to minimize off-target effects.

Genular Protein ID: 2745982570

Symbol: NPY_HUMAN

Name: Pro-neuropeptide Y

UniProtKB Accession Codes:

P01303

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 5 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EMBL 7 EMDB 4 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 6589611

Title: Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine.

PubMed ID: 6589611

DOI: 10.1073/pnas.81.14.4577

PubMed ID: 2427515

Title: Characterization, sequence, and expression of the cloned human neuropeptide Y gene.

PubMed ID: 2427515

DOI: 10.1016/s0021-9258(18)67189-3

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: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

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: 3839058

Title: Presence of the predicted C-flanking peptide of neuropeptide Y (CPON) in tissue extracts.

PubMed ID: 3839058

DOI: 10.1016/0143-4179(85)90100-3

PubMed ID: 21314817

Title: Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are novel substrates of fibroblast activation protein-alpha.

PubMed ID: 21314817

DOI: 10.1111/j.1742-4658.2011.08051.x

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 1425680

Title: Solution conformation of human neuropeptide Y by 1H nuclear magnetic resonance and restrained molecular dynamics.

PubMed ID: 1425680

DOI: 10.1111/j.1432-1033.1992.tb17346.x

PubMed ID: 9008359

Title: Solution structure of human neuropeptide Y.

PubMed ID: 9008359

DOI: 10.1007/bf00228141

PubMed ID: 10561544

Title: Helical structure and self-association in a 13 residue neuropeptide Y Y2 receptor agonist: relationship to biological activity.

PubMed ID: 10561544

DOI: 10.1016/s0167-4838(99)00214-9

Sequence Information:

  • Length: 97
  • Mass: 10851
  • Checksum: 832CF124321718F2
  • Sequence:
    • MLGNKRLGLS GLTLALSLLV CLGALAEAYP SKPDNPGEDA PAEDMARYYS ALRHYINLIT 
RQRYGKRSSP ETLISDLLMR ESTENVPRTR LEDPAMW