The reference OMIM entry for this protein is 601484

Selenoprotein p, plasma, 1; sepp1

CLONING

Hill et al. (1993) cloned human selenoprotein P from a liver cDNA library. The human open reading frame is 69% identical to that of rat selenoprotein P and the predicted proteins share 72% amino acid identity.

GENE FUNCTION

Selenium is an essential trace element that is incorporated as selenocysteine into the primary structure of selenoproteins. There are at least 10 animal selenoproteins. Nutritional deficiency of selenium decreases selenoprotein concentrations and leads to pathologic conditions. Human populations that are selenium deficient are susceptible to the development of Keshan disease, a cardiomyopathy of children reported in selenium-deficient areas of China (Keshan Disease Research Group of the Chinese Academy of Medical Sciences, 1979). Hill et al. (1996) cited animal studies that have demonstrated roles for selenium in oxidant defense, thyroid hormone metabolism, and defense against viral infections. Selenoproteins presumably mediate these biologic effects. Human selenoproteins include glutathione peroxidase-1 (138320), thioredoxin reductase (601112), glutathione peroxidase-2 (138319), glutathione peroxidase-3 (138321), thyroxine deiodinase type 1 (147892), and mitochondrial capsule selenoprotein (601148). Most of the known selenoproteins are members of the glutathione peroxidase or iodothyronine deiodinase families. Hill et al. (1996) stated that selenoprotein P (SEPP1) is a major selenoprotein that is not a member of those families. It is an extracellular glycoprotein that is present in several isoforms and is the only selenoprotein known to contain multiple selenocysteine residues (Hill et al., 1993). It is a heparin-binding protein that appears to be associated with endothelial cells and has been implicated as an oxidant defense in the extracellular space. By microarray analysis, Kabuyama et al. (2007) found that expression of SEPP1 was significantly upregulated in 2 myofibroblast cell lines established from patients with idiopathic pulmonary fibrosis (IPF; 178500) compared with a human embryonic lung fibroblast cell line. Immunohistochemical analysis showed abundant SEPP1 expression in fibrotic regions and epithelial cells in lungs of IPF patients, but not in normal lung parenchyma. IPF myofibroblasts showed enhanced production of lipid hydroperoxides, and knockdown of SEPP1 via RNA interference resulted in increased lipid hydroperoxide production and reduced myofibroblast viability. Overexpression of SEPP1 in retinal pigment epithelial cells suppressed hydrogen peroxide-induced activation of JNK (MAPK8; 601158) and p38 (MAPK14; 600289). Kabuyama et al. (2007) concluded that SEPP1 functions as an antiapoptotic factor against oxidative stress.

MAPPING

Hill et al. (1996) mapped the SEPP1 gene to chromosome 5 by Southern analysis of 2 somatic cell hybrid DNA panels using as a probe their liver cDNA library clone. They narrowed the assignment to 5q31 by fluorescence in situ hybridization. Only 1 SEPP1 locus was detected. Although there is evidence of several isoforms of the protein, all of them share the same N-terminal sequence and therefore are likely products of the same gene (Chittum et al., 1996). Hill et al. (1996) commented that limb-girdle muscular dystrophy type 1A(LGMD1A; 159000) maps to the distal portion of 5q. They noted that since selenium deficiency is associated with nutritional muscular dystrophies in several species, it might be of interest to evaluate SEPP1 in th ... More on the omim web site

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Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 601484 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).