Perilipin 4, also known as S3-12, is a protein that in humans is encoded by the PLIN4 gene on chromosome 19.[5][6] It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue.[7] PLIN4 coats lipid droplets in adipocytes to protect them from lipases.[8][9] The PLIN4 gene may be associated with insulin resistance and obesity risk.[10]
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| Aliases | PLIN4, KIAA1881, S3-12, perilipin 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 613247; MGI: 1929709; HomoloGene: 69311; GeneCards: PLIN4; OMA:PLIN4 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure
editGene
editThe PLIN4 gene resides on chromosome 19 at the band 19p13.3 and contains 9 exons.[5]
Protein
editThis protein belongs to the perilipin family and contains 27 33-amino acid approximate tandem repeats.[11] It is also one of the perilipin members of the PATS (PLIN, ADFP, TIP47, S3-12) family, which is named after structural proteins that share high amino acid sequence similarity and associate with lipid droplets.[6] It shares a conserved C-terminal of 14 amino acid residues that folds into a hydrophobic cleft with other PATS members; however, it is missing the conserved N-terminal region of approximately 100 amino acid residues. Within the sequence of 33-amino acid repeats, PLIN4 contains a long stretch of imperfect 11-mer repeats predicted to form amphipathic helices with three helical turns per 11 amino acid residues. This 11-mer repeats tract is proposed to anchor the protein to the phospholipid monolayer of lipid droplets for its assembly, though no targeting sequence has yet been found in PLIN4.[7]
Function
editPLIN4 is a member of the perilipin family, a group of proteins that coat lipid droplets in adipocytes,[8] the adipose tissue cells that are responsible for storing fat. Perilipin acts as a protective coating from the body’s natural lipases, such as hormone-sensitive lipase,[9] which break triglycerides into glycerol and free fatty acids for use in metabolism, a process called lipolysis.[12] In humans, perilipin is expressed as 5 different isoforms; it is currently understood that the level of expression for each isoform is dependent on factors such as sex, body mass index, and level of endurance exercise.[13]
PLIN4 is hyperphosphorylated by PKA following β-adrenergic receptor activation. Phosphorylated perilipin changes conformation, exposing the stored lipids to hormone-sensitive lipase-mediated lipolysis. Although PKA also phosphorylates hormone-sensitive lipase, which can increase its activity, the more than 50-fold increase in fat mobilization (triggered by epinephrine) is primarily due to perilipin phosphorylation.
Clinical significance
editThe proteins in the Perilipin family are crucial regulators of lipid storage.[12] PLIN4 expression is elevated in obese animals and humans.
The PLIN4 gene, along with PLIN2, PLIN3, and PLIN5, have been associated with variance in body-weight regulation and may be a genetic influence on obesity risk in humans.[10]
Interactions
editPLIN4 has been shown to interact with Caspase 8 and Ubiquitin C.[14]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000167676 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002831 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: Perilipin 4".
- ^ a b Cusano NE, Kiel DP, Demissie S, Karasik D, Adrienne Cupples L, Corella D, Gao Q, Richardson K, Yiannakouris N, Ordovas JM (February 2012). "A Polymorphism in a gene encoding Perilipin 4 is associated with height but not with bone measures in individuals from the Framingham Osteoporosis Study". Calcified Tissue International. 90 (2): 96–107. doi:10.1007/s00223-011-9552-7. PMC 3628693. PMID 22210160.
- ^ a b Brasaemle DL (December 2007). "Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis". Journal of Lipid Research. 48 (12): 2547–59. doi:10.1194/jlr.R700014-JLR200. PMID 17878492.
- ^ a b Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C (June 1991). "Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets". The Journal of Biological Chemistry. 266 (17): 11341–6. doi:10.1016/S0021-9258(18)99168-4. PMID 2040638.
- ^ a b Wong K (2000-11-29). "Making Fat-proof Mice". Scientific American. Retrieved 2009-05-22.
- ^ a b Soenen S, Mariman EC, Vogels N, Bouwman FG, den Hoed M, Brown L, Westerterp-Plantenga MS (March 2009). "Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance". Physiology & Behavior. 96 (4–5): 723–8. doi:10.1016/j.physbeh.2009.01.011. PMID 19385027. S2CID 24747708.
- ^ Universal protein resource accession number Q96Q06 for "PLIN4 - Perilipin-4 - Homo sapiens - PLIN4 gene & protein" at UniProt.
- ^ a b Wolins NE, Skinner JR, Schoenfish MJ, Tzekov A, Bensch KG, Bickel PE (September 2003). "Adipocyte protein S3-12 coats nascent lipid droplets". The Journal of Biological Chemistry. 278 (39): 37713–21. doi:10.1074/jbc.M304025200. PMID 12840023.
- ^ Peters SJ, Samjoo IA, Devries MC, Stevic I, Robertshaw HA, Tarnopolsky MA (August 2012). "Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training". Applied Physiology, Nutrition, and Metabolism. 37 (4): 724–35. doi:10.1139/h2012-059. PMID 22667335.
- ^ "PLIN4 Results Summary". BioGrid. Tyerslab.com. Retrieved 18 May 2015.
Further reading
edit- Richardson K, Louie-Gao Q, Arnett DK, Parnell LD, Lai CQ, Davalos A, Fox CS, Demissie S, Cupples LA, Fernandez-Hernando C, Ordovas JM (April 2011). "The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site". PLOS ONE. 6 (4): e17944. Bibcode:2011PLoSO...617944R. doi:10.1371/journal.pone.0017944. PMC 3080366. PMID 21533135.
- Sone Y, Yamaguchi K, Fujiwara A, Kido T, Kawahara K, Ishiwaki A, Kondo K, Morita Y, Tominaga N, Otsuka Y (2010). "Association of lifestyle factors, polymorphisms in adiponectin, perilipin and hormone sensitive lipase, and clinical markers in Japanese males". Journal of Nutritional Science and Vitaminology. 56 (2): 123–31. doi:10.3177/jnsv.56.123. PMID 20495294.
- Kimmel AR, Brasaemle DL, McAndrews-Hill M, Sztalryd C, Londos C (March 2010). "Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins". Journal of Lipid Research. 51 (3): 468–71. doi:10.1194/jlr.R000034. PMC 2817576. PMID 19638644.
- Wolins NE, Skinner JR, Schoenfish MJ, Tzekov A, Bensch KG, Bickel PE (September 2003). "Adipocyte protein S3-12 coats nascent lipid droplets". The Journal of Biological Chemistry. 278 (39): 37713–21. doi:10.1074/jbc.M304025200. PMID 12840023.
- Nagase T, Kikuno R, Ohara O (August 2001). "Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins". DNA Research. 8 (4): 179–87. doi:10.1093/dnares/8.4.179. PMID 11572484.
- Cusano NE, Kiel DP, Demissie S, Karasik D, Adrienne Cupples L, Corella D, Gao Q, Richardson K, Yiannakouris N, Ordovas JM (February 2012). "A Polymorphism in a gene encoding Perilipin 4 is associated with height but not with bone measures in individuals from the Framingham Osteoporosis Study". Calcified Tissue International. 90 (2): 96–107. doi:10.1007/s00223-011-9552-7. PMC 3628693. PMID 22210160.
- Peters SJ, Samjoo IA, Devries MC, Stevic I, Robertshaw HA, Tarnopolsky MA (August 2012). "Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training". Applied Physiology, Nutrition, and Metabolism. 37 (4): 724–35. doi:10.1139/h2012-059. PMID 22667335.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.