Leptin receptor

LEPR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3V6O
Identifiers
Aliases	LEPR, CD295, LEP-R, LEPRD, OB-R, OBR, leptin receptor
External IDs	OMIM: 601007; MGI: 104993; HomoloGene: 1731; GeneCards: LEPR; OMA:LEPR - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.3 Start 65,420,652 bp[1] End 65,641,559 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 C6|4 46.96 cM Start 101,574,601 bp[2] End 101,672,549 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in trabecular bone Epithelium of choroid plexus trigeminal ganglion pericardium skin of hip oral cavity mucosa of pharynx lower lobe of lung skin of thigh urethra Top expressed in lumbar spinal ganglion Epithelium of choroid plexus dermis right lung mesenteric lymph nodes aortic valve membranous bone Dermatocranium right lung lobe Paneth cell More reference expression data BioGPS n/a
Gene ontology Molecular function leptin receptor activity protein binding identical protein binding cytokine receptor activity transmembrane signaling receptor activity peptide hormone binding cytokine binding Cellular component integral component of membrane membrane receptor complex plasma membrane extracellular region basolateral plasma membrane external side of plasma membrane Biological process sexual reproduction glucose homeostasis leptin-mediated signaling pathway cholesterol metabolic process negative regulation of hydrolase activity regulation of feeding behavior multicellular organism development negative regulation of gluconeogenesis cell surface receptor signaling pathway T cell differentiation angiogenesis energy homeostasis bone growth energy reserve metabolic process response to leptin negative regulation of autophagy regulation of bone remodeling phagocytosis positive regulation of cold-induced thermogenesis glycogen metabolic process glial cell proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3953 16847 Ensembl ENSG00000116678 ENSMUSG00000057722 UniProt P48357 P48356 RefSeq (mRNA) NM_002303 NM_001003679 NM_001003680 NM_001198687 NM_001198688 NM_001198689 NM_001122899 NM_010704 NM_146146 RefSeq (protein) NP_001003679 NP_001003680 NP_001185616 NP_001185617 NP_001185618 NP_002294 NP_001116371 NP_034834 NP_666258 Location (UCSC) Chr 1: 65.42 – 65.64 Mb Chr 4: 101.57 – 101.67 Mb PubMed search [3] [4]
Wikidata
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Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor,^[5] a protein that in humans is encoded by the LEPR gene.^[6][7] LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295 (cluster of differentiation 295). Its location is the cell membrane, and it has extracellular, trans-membrane and intracellular sections (protein regions).

The Leptin Receptor was discovered in 1995 by Louis Tartaglia and his colleagues at Millennium Pharmaceuticals.^[8] This same team demonstrated the leptin receptor was expressed by the mouse db gene.^[9] Furthermore, in 1996, after co-discovering the Leptin gene with Jeffrey Friedman et al. in 1994, (which involved a reverse genetic/positional cloning strategy to clone ob and db), Rudolph Leibel, working with collaborators also at Millennium Pharmaceuticals and colleague Streamson Chua, confirmed cloning of the leptin receptor by demonstrating that an apparent leptin receptor cloned from a choroid plexus library using leptin as ligand, mapped to a physical map that included db and fa.^[10][11]

Like other cytokine receptors, Leptin receptor protein has three different regions: i) extracellular, ii) trans-membrane, and iii) intracellular. The extracellular part has 5 functional domains:^[12] i) membrane distal 1st cytokine receptor homology (CRH1), ii) Immunoglobulin like (Ig), iii) 2nd cytokine receptor homology (CRH2) and iv) two membrane proximal fibronectine type-III (FNIII) domains. CRH1 domains is not essential for Leptin binding, but may have regulatory roles.^[12] Ig domain interacts with Leptin and is essential for conformational change in the receptor upon ligand binding.^[12] CRH2 is essential for leptin binding, deletion of this domain abolishes the leptin binding.^[12] FNIII domains are essential for receptor activation upon leptin binding.^[12] The structure of the quaternary complex of the complete extracellular part in complex with the cognate ligand Leptin (i.e. 2 receptor and 2 ligand) has been solved by both electron microscopy^[13] and SAXS.^[14]

The leptin hormone regulates adipose-tissue mass through hypothalamus effects on hunger and energy use. It acts through the leptin receptor (LEP-R), a single-transmembrane-domain receptor of the cytokine receptor family.^[15] In hypothalamic neurons, adequate leptin receptor function and subsequent regulation of energy metabolism and body weight depends on interactions of the receptor with gangliosides in the cell membrane.^[16]

Variations in the leptin receptor have been associated with obesity^[17][18] and with increased susceptibility to Entamoeba histolytica infections.^[19]

The db/db mouse is a model of obesity, diabetes, and dyslipidemia wherein leptin receptor activity is deficient because the mice are homozygous for a point mutation in the gene for the leptin receptor.^[20] In db/db mice, induced swimming helped to overcome obesity by upregulating uncoupling proteins.^[21]

The leptin hormone and its receptor, also known as maternal plasma leptin, play developmental roles during pregnancy.^[22] Leptin receptors have been identified in the placenta of pregnant women and also in fetal tissues.^[23] Those leptin receptors are secreted by the placenta; they increase leptin levels during pregnancy thereby aiding the fetal development.^[23]

• LEPR+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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