Perilipin-4

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]

PLIN4
Identifiers
AliasesPLIN4, KIAA1881, S3-12, perilipin 4
External IDsOMIM: 613247 MGI: 1929709 HomoloGene: 69311 GeneCards: PLIN4
Gene location (Human)
Chr.Chromosome 19 (human)[1]
Band19p13.3Start4,502,180 bp[1]
End4,518,465 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

729359

57435

Ensembl

ENSG00000167676

ENSMUSG00000002831

UniProt

Q96Q06

O88492

RefSeq (mRNA)

NM_001080400
NM_001367868

NM_020568
NM_001372234

RefSeq (protein)

NP_001354797

NP_065593
NP_001359163

Location (UCSC)Chr 19: 4.5 – 4.52 MbChr 17: 56.1 – 56.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

Gene

The PLIN4 gene resides on chromosome 19 at the band 19p13.3 and contains 9 exons.[5]

Protein

This 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

PLIN4 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

The proteins in the Perilipin family are crucial regulators of lipid storage.[12] PLIN4 expression is elevated in obese animals and humans. Perilipin-null mice eat more food than wild-type mice, but gain 1/3 less fat than wild-type mice on the same diet; perilipin-null mice are thinner, with more lean muscle mass.[14] Perilipin-null mice also exhibit enhanced leptin production and a greater tendency to develop insulin resistance than wild-type mice.

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

PLIN4 has been shown to interact with Caspase 8 and Ubiquitin C.[15]

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References
  1. GRCh38: Ensembl release 89: ENSG00000167676 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000002831 - 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. "Entrez Gene: Perilipin 4".
  6. 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.
  7. 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.
  8. 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. PMID 2040638.
  9. Wong K (2000-11-29). "Making Fat-proof Mice". Scientific American. Retrieved 2009-05-22.
  10. 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.
  11. Universal protein resource accession number Q96Q06 for "PLIN4 - Perilipin-4 - Homo sapiens - PLIN4 gene & protein" at UniProt.
  12. 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.
  13. 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.
  14. telegraph.co.uk, 19 June 2001, Highfield, Roger (2000-11-29). "Couch potato mice discover the lazy way to stay slim". The Daily Telegraph. London. Retrieved 2008-09-03.
  15. "PLIN4 Results Summary". BioGrid. Tyerslab.com. Retrieved 18 May 2015.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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