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PLIN4
Identifiers
Aliases	PLIN4, KIAA1881, S3-12, perilipin 4
External IDs	OMIM: 613247; MGI: 1929709; HomoloGene: 69311; GeneCards: PLIN4; OMA:PLIN4 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19p13.3 Start 4,502,192 bp End 4,518,486 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17|17 D Start 56,407,591 bp End 56,416,803 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in subcutaneous adipose tissue muscle of thigh apex of heart gastrocnemius muscle cardiac muscle tissue of right atrium abdominal fat myocardium of left ventricle pericardium Skeletal muscle tissue of rectus abdominis Skeletal muscle tissue of biceps brachii Top expressed in white adipose tissue subcutaneous adipose tissue muscle of thigh lactiferous gland brown adipose tissue tunica media of zone of aorta tunica adventitia of aorta ankle intercostal muscle medial head of gastrocnemius muscle More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 729359 57435 Ensembl ENSG00000167676 ENSMUSG00000002831 UniProt Q96Q06 O88492 RefSeq (mRNA) NM_001080400 NM_001367868 NM_001393888 NM_001393889 NM_001393890 NM_001393891 NM_020568 NM_001372234 RefSeq (protein) NP_001354797 NP_065593 NP_001359163 Location (UCSC) Chr 19: 4.5 – 4.52 Mb Chr 17: 56.41 – 56.42 Mb PubMed search
Wikidata
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Perilipin 4, also known as S3-12, is a protein that in humans is encoded by the PLIN4 gene on chromosome 19. It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue. PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The PLIN4 gene may be associated with insulin resistance and obesity risk.

Structure

Gene

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

Protein

This protein belongs to the perilipin family and contains 27 33-amino acid approximate tandem repeats. 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. 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.

Function

PLIN4 is a member of the perilipin family, a group of proteins that coat lipid droplets in adipocytes, 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, which break triglycerides into glycerol and free fatty acids for use in metabolism, a process called lipolysis. 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.

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. 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.

Interactions

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

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. doi:10.1016/S0021-9258(18)99168-4. 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. S2CID 24747708.
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. "PLIN4 Results Summary". BioGrid. Tyerslab.com. Retrieved 18 May 2015.

Further reading

• 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.

• Genes on human chromosome 19