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.[5][6][7]

PNPLA3
Identifiers
AliasesPNPLA3, ADPN, C22orf20, iPLA(2)epsilon, patatin like phospholipase domain containing 3
External IDsOMIM: 609567 MGI: 2151796 HomoloGene: 11883 GeneCards: PNPLA3
Gene location (Human)
Chr.Chromosome 22 (human)[1]
Band22q13.31Start43,923,792 bp[1]
End43,964,488 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

80339

116939

Ensembl

ENSG00000100344

ENSMUSG00000041653

UniProt

Q9NST1

Q91WW7

RefSeq (mRNA)

NM_025225

NM_054088

RefSeq (protein)

NP_079501

NP_473429

Location (UCSC)Chr 22: 43.92 – 43.96 MbChr 15: 84.17 – 84.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.[7]

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 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.[8] 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.[9]

References
  1. GRCh38: Ensembl release 89: ENSG00000100344 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000041653 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (September 2006). "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
  6. Kienesberger PC, Oberer M, Lass A, Zechner R (April 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research. 50 Suppl: S63-8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
  7. "Entrez Gene: PNPLA3 patatin-like phospholipase domain containing 3".
  8. Stickel F, Hampe J (January 2012). "Genetic determinants of alcoholic liver disease". Gut. 61 (1): 150–9. doi:10.1136/gutjnl-2011-301239. PMID 22110053.
  9. Pingitore P, Romeo S (June 2019). "The role of PNPLA3 in health and disease". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1864 (6): 900–906. doi:10.1016/j.bbalip.2018.06.018. PMID 29935383.

Further reading
  • Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (December 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
  • Collins JE, Goward ME, Cole CG, Smink LJ, Huckle EJ, Knowles S, Bye JM, Beare DM, Dunham I (January 2003). "Reevaluating human gene annotation: a second-generation analysis of chromosome 22". Genome Research. 13 (1): 27–36. doi:10.1101/gr.695703. PMC 430954. PMID 12529303.
  • Liu YM, Moldes M, Bastard JP, Bruckert E, Viguerie N, Hainque B, Basdevant A, Langin D, Pairault J, Clément K (June 2004). "Adiponutrin: A new gene regulated by energy balance in human adipose tissue". The Journal of Clinical Endocrinology and Metabolism. 89 (6): 2684–9. doi:10.1210/jc.2003-031978. PMID 15181042.
  • Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW (November 2004). "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. doi:10.1074/jbc.M407841200. PMID 15364929.
  • Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
  • Lake AC, Sun Y, Li JL, Kim JE, Johnson JW, Li D, Revett T, Shih HH, Liu W, Paulsen JE, Gimeno RE (November 2005). "Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members". Journal of Lipid Research. 46 (11): 2477–87. doi:10.1194/jlr.M500290-JLR200. PMID 16150821.


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