Lepr
Domain
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.
Function
Receptor for hormone LEP/leptin (Probable) (PubMed:11861497). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS (PubMed:10799542, PubMed:11861497, PubMed:11923481, PubMed:25383904). In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (PubMed:10660043, PubMed:12594516). In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity (PubMed:11923481, PubMed:25383904). Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis (PubMed:12594516). Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus (PubMed:25383904). Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T-cells. Leptin increases Th1 and suppresses Th2 cytokine production (PubMed:9732873).
Isoform A
May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis (PubMed:17620316, PubMed:20223942). Does not induce phosphorylation of and activate STAT3 (PubMed:11923481, PubMed:20223942).
Isoform E
Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.
Post-translational modifications
On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-985 is required for complete binding and activation of PTPN11, ERK/FOS activation,for interaction with SOCS3 and SOCS3 mediated inhibition of leptin signaling. Phosphorylation on Tyr-1138 is required for STAT3 binding/activation. Phosphorylation of Tyr-1077 has a more accessory role.
Sequence Similarities
Belongs to the type I cytokine receptor family. Type 2 subfamily.
Tissue Specificity
Isoform A: highest level of expression in lung and kidney, also present in heart, brain, spleen, liver, muscle, choroid plexus and hypothalamus. Isoform B: highest levels of expression in hypothalamus and lower levels in brain, testes and adipose tissue. Expressed by neurons of the parabrachial nucleus (PubMed:25383904). Expressed by peripheral blood mononuclear cells and CD4(+) T-cells (PubMed:9732873). Isoform E: expressed in adipose tissue, liver, hypothalamus, cerebral microvessels, heart, and testes (PubMed:17620316).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Basolateral cell membrane
- Isoform E
- Secreted
Alternative names
CD295, Db, Obr, Lepr, Leptin receptor, LEP-R, B219, OB receptor, OB-R