Seipin

Seipin is a homo-oligomeric integral membrane protein in the endoplasmic reticulum (ER) that concentrates at junctions with cytoplasmic lipid droplets (LDs). Alternatively, seipin can be referred to as Bernardinelli-Seip congenital lipodystrophy type 2 protein (BSCL2), and it is encoded by the corresponding gene of the same name, i.e. BSCL2. At protein level, seipin is expressed in cortical neurons in the frontal lobes, as well as motor neurons in the spinal cord. It is highly expressed in areas like the brain, testis and adipose tissue. Seipin's function is still unclear but it has been localized close to lipid droplets, and cells knocked out in seipin which have anomalous droplets. Hence, recent evidence suggests that seipin plays a crucial role in lipid droplet biogenesis. Seipin is a homo-oligomeric integral membrane protein in the endoplasmic reticulum (ER) that concentrates at junctions with cytoplasmic lipid droplets (LDs). Alternatively, seipin can be referred to as Bernardinelli-Seip congenital lipodystrophy type 2 protein (BSCL2), and it is encoded by the corresponding gene of the same name, i.e. BSCL2. At protein level, seipin is expressed in cortical neurons in the frontal lobes, as well as motor neurons in the spinal cord. It is highly expressed in areas like the brain, testis and adipose tissue. Seipin's function is still unclear but it has been localized close to lipid droplets, and cells knocked out in seipin which have anomalous droplets. Hence, recent evidence suggests that seipin plays a crucial role in lipid droplet biogenesis. Though it was initially dubbed 'mysterious protein', recent empirical studies are gradually starting to unveil some of seipin's most compelling physiological functions. Among these, the following have been identified: central regulation of energy homeostasis, lipid catabolism (essential for adipocyte differentiation), lipid storage and lipid droplet maintenance, as well as prevention of ectopic lipid droplet formation in non-adipose tissues. Additionally, mutations of BSCL2 have been recently linked to the Silver-Syndrome and Celia's Encephalopathy. The seipin gene BSCL2 was originally identified in mammals and the fruit fly, and later extended to fungi and plants. The human seipin gene is located on chromosome 11q13, with protein coding on the Crick strand. There are three validated coding transcripts in GenBank. The primary transcript originally described, contained 11 exons with protein coding beginning on exon 2 and ending in exon 11 (transcript variant 2), resulting in a 398 amino acid protein with two strongly predicted transmembrane domains (TMDs), coded in exons 2 and 7 (isoform 2). However, a longer transcript (variant 1) is generated with an alternative first exon containing a translational start site that results in an additional 64 amino acids at the N-terminal extension, 462 amino acids in total (isoform 1). A third coding transcript (variant 3) splices out exon 7 and produces a shortened and altered carboxy terminus in exon 10, generating a protein of 287 amino acids (isoform 3). The secondary structure of seipin includes a conserved central core domain, and diverse cytosolic N- and C-termini.