Biology:PNPLA3
 Generic protein structure example |
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.[1][2][3]
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.[3]
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, putative 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 of 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.[4] A mutation of isoleucine to methionine (I[ATC]>M[ATG]) SNP rs738409 has been confirmed to increase susceptibility to non-alcoholic liver disease and also to have effects in diabetes.[5]
References
- ↑ "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research 47 (9): 1940–9. September 2006. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
- ↑ "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research 50 Suppl (Suppl): S63-8. April 2009. doi:10.1194/jlr.R800082-JLR200. PMID 19029121.
- ↑ 3.0 3.1 "Entrez Gene: PNPLA3 patatin-like phospholipase domain containing 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80339.
- ↑ "Genetic determinants of alcoholic liver disease". Gut 61 (1): 150–9. January 2012. doi:10.1136/gutjnl-2011-301239. PMID 22110053.
- ↑ "The role of PNPLA3 in health and disease". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1864 (6): 900–906. June 2019. doi:10.1016/j.bbalip.2018.06.018. PMID 29935383.
Further reading
- "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. December 1999. doi:10.1038/990031. PMID 10591208. Bibcode: 1999Natur.402..489D.
- "Reevaluating human gene annotation: a second-generation analysis of chromosome 22". Genome Research 13 (1): 27–36. January 2003. doi:10.1101/gr.695703. PMID 12529303.
- "Adiponutrin: A new gene regulated by energy balance in human adipose tissue". The Journal of Clinical Endocrinology and Metabolism 89 (6): 2684–9. June 2004. doi:10.1210/jc.2003-031978. PMID 15181042.
- "Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities". The Journal of Biological Chemistry 279 (47): 48968–75. November 2004. doi:10.1074/jbc.M407841200. PMID 15364929.
- "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology 5 (10): R84. 2005. doi:10.1186/gb-2004-5-10-r84. PMID 15461802.
- "Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members". Journal of Lipid Research 46 (11): 2477–87. November 2005. doi:10.1194/jlr.M500290-JLR200. PMID 16150821.
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