PNPLA3

Patatin-like phospholipase domain-containing protein 3 (PNPLA3) also known as adiponutrin (ADPN), acylglycerol O-acyltransferase or calcium-independent phospholipase A2-epsilon (iPLA2-epsilon) is an enzyme that in humans is encoded by the PNPLA3 gene.

PNPLA3
Identifiers
Aliases	PNPLA3, ADPN, C22orf20, iPLA(2)epsilon, patatin like phospholipase domain containing 3
External IDs	OMIM: 609567; MGI: 2151796; HomoloGene: 11883; GeneCards: PNPLA3; OMA:PNPLA3 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) Band 22q13.31 Start 43,923,792 bp End 43,964,488 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15|15 E2 Start 84,052,038 bp End 84,071,437 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium buccal mucosa cell right lobe of liver secondary oocyte tibia skin of leg vulva testicle skin of abdomen middle temporal gyrus Top expressed in white adipose tissue neural layer of retina zone of skin esophagus lens lip skeletal muscle tissue left lung quadriceps femoris muscle morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function mono-olein transacylation activity transferase activity phospholipase A2 activity acyltransferase activity hydrolase activity diolein transacylation activity acylglycerol O-acyltransferase activity lipoprotein lipase activity triglyceride lipase activity lysophosphatidic acid binding long-chain fatty acyl-CoA binding lysophosphatidic acid acyltransferase activity 1-acylglycerol-3-phosphate O-acyltransferase activity Cellular component integral component of membrane endoplasmic reticulum membrane cytoplasm lipid droplet membrane Biological process lipid catabolic process triglyceride biosynthetic process metabolism acylglycerol acyl-chain remodeling lipid metabolism triglyceride catabolic process triglyceride acyl-chain remodeling lipid homeostasis long-chain fatty acid metabolic process glycerophospholipid metabolic process phosphatidic acid biosynthetic process lipid droplet organization phospholipid biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 80339 116939 Ensembl ENSG00000100344 ENSMUSG00000041653 UniProt Q9NST1 Q91WW7 RefSeq (mRNA) NM_025225 NM_054088 RefSeq (protein) NP_079501 NP_473429 NP_001395268 NP_001395269 NP_001395270 NP_001395271 Location (UCSC) Chr 22: 43.92 – 43.96 Mb Chr 15: 84.05 – 84.07 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

Adiponutrin is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes.

Genomics

The gene is located on the long arm of chromosome 22 at band 13.31 (22q13.31). It lies on the Watson (plus) strand and is 40,750 bases in length.

Upstream of the gene putaive binding sites for several transcription factors have been identified. These include PPAR-gamma, POU2F1, and POU2F2. If any of these transcriptions factors are actually involved in the regulation of this gene is not known at present.

Biochemistry

The recommended name for the gene product is patatin-like phospholipase domain-containing protein 3. It is a Single-pass type II membrane protein and is a multifunctional enzyme with both triacylglycerol lipase and acylglycerol O-acyltransferase activities. It is involved in the triacylglycerol hydrolysis in adipocytes and may play a role in energy metabolism.

The mature protein is 481 amino acids in length and the predicted molecular weight is 52.865 kiloDaltons (kDa). Two the isoforms have been described but the functional significance - if any - of these forms is not known.

Clinical relevance

An association between alcoholic liver disease in caucasians and variations in this gene has been confirmed. A mutation of isoleucine to methionine (I[ATC]>M[ATG]) SNP rs738409 has been confirmed to increase susceptibility to alcoholic liver disease and also to have effects in diabetes.

Further reading

• Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Collins JE, Goward ME, Cole CG, et al. (2003). "Reevaluating human gene annotation: a second-generation analysis of chromosome 22". Genome Res. 13 (1): 27–36. doi:10.1101/gr.695703. PMC 430954. PMID 12529303.
• Liu YM, Moldes M, Bastard JP, et al. (2004). "Adiponutrin: A new gene regulated by energy balance in human adipose tissue". J. Clin. Endocrinol. Metab. 89 (6): 2684–9. doi:10.1210/jc.2003-031978. PMID 15181042.
• Jenkins CM, Mancuso DJ, Yan W, et al. (2005). "Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities". J. Biol. Chem. 279 (47): 48968–75. doi:10.1074/jbc.M407841200. PMID 15364929.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Collins JE, Wright CL, Edwards CA, et al. (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Lake AC, Sun Y, Li JL, et al. (2006). "Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members". J. Lipid Res. 46 (11): 2477–87. doi:10.1194/jlr.M500290-JLR200. PMID 16150821.{{cite journal}}: CS1 maint: unflagged free DOI (link)