The reference OMIM entry for this protein is 613461

Leptin receptor overlapping transcript; leprot
Leptin receptor gene-related protein; obrgrp

DESCRIPTION

LEPROT is associated with the Golgi complex and endosomes and has a role in cell surface expression of growth hormone receptor (GHR; 600946) and leptin receptor (OBR, or LEPR; 601007), thereby altering receptor-mediated cell signaling (Couturier et al., 2007; Touvier et al., 2009).

CLONING

By examining an EST database, Bailleul et al. (1997) identified LEPROT, which they called OBRGRP. OBRGRP and OBR share the same 5-prime UTR, but the initiating AUG codon for OBRGRP is upstream of that used by OBR, and OBRGRP is read in a different reading frame. The deduced 131-amino acid OBRGRP protein has a calculated molecular mass of 14.3 kD. Northern blot analysis detected OBRGRP transcripts of 1.3 to 2.4 kb in all 8 human tissues examined, with highest expression in heart and placenta. PCR analysis detected expression in all human cell lines examined and in mouse lung and kidney. The expression pattern of OBRGRP and OBR was similar, and Bailleul et al. (1997) suggested that the 2 transcripts may use the same promoter. Database analysis revealed OBRGRP orthologs in yeast and nematode, suggesting phylogenetic conservation. Using immunofluorescence analysis, Couturier et al. (2007) found that endogenous OBRGRP was expressed in the Golgi complex and endosomes of HeLa cells.

GENE FUNCTION

Leptin (LEP; 164160) is the crucial adipostatic hormone that controls food intake and body weight through activation of OBR in the hypothalamic arcuate nucleus. By injection of lentivirus carrying short hairpin RNA directed against Obrgrp into the mouse arcuate nucleus, Couturier et al. (2007) showed that Obrgrp negatively regulated leptin signaling. Silencing of Obrgrp in the hypothalamic arcuate nucleus also prevented the development of high-fat diet-induced obesity. Coimmunoprecipitation analysis of cotransfected HeLa cells showed that Obrgrp interacted directly with Obr, and silencing of endogenous HeLa cell OBRGRP increased the cell surface expression of OBR. Couturier et al. (2007) concluded that OBRGRP regulates the distribution of OBR between the plasma membrane and intracellular compartments. During periods of reduced nutrient availability, the liver becomes resistant to the action of growth hormone (GH1; 139250). Touvier et al. (2009) found that transgenic mice expressing human LEPROT or LEPROTL1 (607338) became growth retarded and that their isolated hepatocytes showed reduced GH-binding capacity and impaired GH-dependent cell signaling. Transgenic mice expressing both LEPROT and LEPROTL1 showed a more severe phenotype and significantly reduced expression of GH-dependent genes. In contrast, knockdown of Leprot or Leprotl1 in a rat hepatocyte cell line elevated GH-binding capacity and GH-dependent cell signaling. Hepatic Leprot and Leprotl1 mRNA expression was increased in mice by fasting and streptozoticin-induced diabetes, whereas insulin treatment of cultured rat hepatocytes had the opposite effect. Touvier et al. (2009) concluded that LEPROT and LEPROTL1 influence liver GH signaling and are involved in nutritional signals, body growth, and metabolism.

GENE STRUCTURE

Bailleul et al. (1997) determined that the LEPROT gene contains 4 exons. The first 2 exons of LEPROT are shared with LEPR, and exons 3 and 4 lie within intron 2 of LEPR.

MAPPING

Bailleul et al. (1997) found that the LEPROT gene overlaps the LEPR gene on chromosome 1p31 and is transcribed in the same direction. ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 613461 was added.

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