1. Gene Aliases

Perilipin 2, ADRP, Adipose Differentiation-Related Protein, Adipophilin, ADFP, Perilipin-2

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=PLIN2&keywords=Plin2]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

Chaperone Mediated Autophagy: In contrary to the vesicle-mediated macroautophagy, the chaperone mediated mechanism of autophagy selectively targets individual proteins to the lysosome for degradation. Chaperones bind intracellular proteins based on recognition motifs and transports them from the cytosol to the lysosomal membrane. Subsequently, the protein is translocated into the lumen for digestion (Cuervo A M et al. 2014, Kaushik S et al. 2018). [https://reactome.org/PathwayBrowser/#/R-HSA-9613829&PATH=R-HSA-9612973]

Late endosomal microautophagy: Microautophagy (MI) is a non-selective autophagic pathway that involves internalisation of cytosolic cargo through invaginations of the lysosomal membrane. MI can be induced by nitrogen starvation and complements other related self-eating processes such as Macroautophagy (MA) and Chaperone Mediated Autophagy (CMA). MI can degrade cell organelles and bulk cytosolic proteins directly via the lysosome and late endosome. MI can also target substrates with KFERQ motifs with the help of HSPA8 (Li W W et al. 2012). [https://reactome.org/PathwayBrowser/#/R-HSA-9615710]

Lipophagy: Triglycerides stored in lipid droplets are hydrolysed under nutrient starvation to release fatty acids for energy. The content of lipid droplets may vary but they are all coated with a protective protein called perilipin. When this protein is degraded, lipid droplets associate with autophagic components and breakdown into fatty acids (Ward C et al. 2016, Schulze R J et al. 2017). This process is termed as lipophagy (Singh R et al. 2009). [https://reactome.org/PathwayBrowser/#/R-HSA-9613354]

PPARA activates gene expression: The set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor elements (PPREs) in their promoters and include: 1) genes involved in fatty acid oxidation and ketogenesis (Acox1, Cyp4a, Acadm, Hmgcs2); 2) genes involved in fatty acid transport (Cd36, , Slc27a1, Fabp1, Cpt1a, Cpt2); 3) genes involved in producing fatty acids and very low density lipoproteins (Me1, Scd1); 4) genes encoding apolipoproteins (Apoa1, Apoa2, Apoa5); 5) genes involved in triglyceride clearance ( Angptl4); 6) genes involved in glycerol metabolism (Gpd1 in mouse); 7) genes involved in glucose metabolism (Pdk4); 8) genes involved in peroxisome proliferation (Pex11a); 9) genes involved in lipid storage (Plin, Adfp). Many other genes are known to be regulated by PPAR-alpha but whether their regulation is direct or indirect remains to be found. These genes include: ACACA, FAS, SREBP1, FADS1, DGAT1, ABCA1, PLTP, ABCB4, UGT2B4, SULT2A1, Pnpla2, Acsl1, Slc27a4, many Acot genes, and others (reviewed in Rakhshandehroo et al. 2010). [https://reactome.org/PathwayBrowser/#/R-HSA-400206&SEL=R-HSA-1989781&PATH=R-HSA-1430728,R-HSA-556833]

GO terms:

cellular response to glucose starvation [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of glucose. GO:0042149]

lipid droplet disassembly [The disaggregation of a lipid particle into its constituent components. GO:1905691]

lipid storage [The accumulation and maintenance in cells or tissues of lipids, compounds soluble in organic solvents but insoluble or sparingly soluble in aqueous solvents. Lipid reserves can be accumulated during early developmental stages for mobilization and utilization at later stages of development. GO:0019915]

long-chain fatty acid transport [The directed movement of a long-chain fatty acid into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. A long-chain fatty acid is a fatty acid with an aliphatic tail of 13 to 21 carbons. GO:0015909]

positive regulation of sequestering of triglyceride [Any process that increases the rate, frequency or extent of sequestering of triglyceride. Triglyceride sequestration is the process of binding or confining any triester of glycerol such that it is separated from other components of a biological system. GO:0010890]

response to organic cyclic compound [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. GO:0014070]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0009410]

MSigDB Signatures:

WP_ADIPOGENESIS: Adipogenesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ADIPOGENESIS.html]

REACTOME_AUTOPHAGY: Autophagy [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_AUTOPHAGY.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene belongs to the perilipin family, members of which coat intracellular lipid storage droplets. This protein is associated with the lipid globule surface membrane material, and maybe involved in development and maintenance of adipose tissue. However, it is not restricted to adipocytes as previously thought, but is found in a wide range of cultured cell lines, including fibroblasts, endothelial and epithelial cells, and tissues, such as lactating mammary gland, adrenal cortex, Sertoli and Leydig cells, and hepatocytes in alcoholic liver cirrhosis, suggesting that it may serve as a marker of lipid accumulation in diverse cell types and diseases. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011]

GeneCards Summary: PLIN2 (Perilipin 2) is a Protein Coding gene. Diseases associated with PLIN2 include Sebaceous Adenocarcinoma and Chanarin-Dorfman Syndrome. Among its related pathways are Selective autophagy and Budding and maturation of HIV virion. An important paralog of this gene is PLIN3.

UniProtKB/Swiss-Prot Summary: Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets.

8. Cellular Location of Gene Product

Cytoplasmic and membranous expression in several tissues. Additional plasma positivity in a few tissues including lactating breast. Localized to the lipid droplets. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000147872/subcellular]

9. Mechanistic Information

Summary

Plin2, encoded by the PLIN2 gene, produces a protein involved in the formation and maintenance of lipid storage droplets, particularly in adipose tissue but also in various other cell types [CS: 10]. This protein, known as adipophilin or ADFP, is critical in lipid metabolism, particularly in regulating lipid accumulation and the stabilization of lipid droplets [CS: 9]. Its expression is modulated by several factors, including PPARgamma activation, fatty acid levels, and hypoxic conditions [CS: 8].

In the context of the colon, Plin2's dysregulation appears to be linked to conditions of stress or disease [CS: 7]. For instance, the activation of PPARgamma, a nuclear receptor involved in adipogenesis and lipid metabolism, upregulates Plin2 expression [CS: 9]. In diseases like ulcerative colitis, PPARgamma activation increases adipophilin mRNA expression and leads to a decrease in inflammatory markers such as TNF-alpha, IL-1beta, and IL-13 [CS: 6]. This suggests that Plin2 expression, stimulated by PPARgamma, may contribute to a protective or mitigating response against inflammation by aiding in lipid accumulation and regulating lipid metabolism [CS: 7]. In contrast, the disruption of Plin2 expression, as seen in mice with a high-fat diet, alters gut microbial communities and affects metabolic pathways, indicating its role in maintaining gut homeostasis under dietary stress [CS: 6]. Thus, the upregulation of Plin2 in response to various stressors in the colon appears to be a cellular mechanism for managing lipid metabolism and storage, potentially as a means to counteract inflammatory and hypoxic stress [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: adipose tissue, liver (tissue enhanced) [https://www.proteinatlas.org/ENSG00000147872/tissue]

Cell type enchanced: extravillous trophoblasts, granulocytes, hepatocytes, syncytiotrophoblasts (cell type enhanced) [https://www.proteinatlas.org/ENSG00000147872/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: