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
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''PNPLA3''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Adiponutrin is a triacylglycerol
lipase
In biochemistry, lipase ( ) refers to a class of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; howe ...
that mediates
triacylglycerol
A triglyceride (from ''tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids.
Triglycerides are the main constituents of body fat in humans and other vertebrates as ...
hydrolysis in
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cell (biology), cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through ...
s. 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
Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 51 million DNA base pairs and representing b ...
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
Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transc ...
,
POU2F1
POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene.
Interactions
POU2F1 has been shown to interact with:
* EPRS,
* Glucocorticoid receptor,
* Glyceraldehyde 3-phosphate dehydrogenase, ...
, and
POU2F2. It is not known at present whether any of these transcriptions factors are actually involved in the regulation of this gene.
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
caucasian
Caucasian may refer to:
Common meanings
*Anything from the Caucasus region or related to it
** Ethnic groups in the Caucasus
** ''Caucasian Exarchate'' (1917–1920), an ecclesiastical exarchate of the Russian Orthodox Church in the Caucasus re ...
s and variations in this gene has been confirmed.
A mutation of isoleucine to methionine (I
TCM
TG SNP rs738409 has been confirmed to increase susceptibility to non-alcoholic liver disease and also to have effects in diabetes.
References
Further reading
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EC 3.1.1
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