LEPR

Leptin (LEP; MIM 164160), an adipocyte-specific hormone that regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure, acts through the leptin receptor (LEPR), a single-transmembrane-domain receptor of the cytokine receptor family.[supplied by OMIM

leptin receptor

Receptor for hormone LEP/leptin (Probable) (PubMed:22405007).
On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. 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 (By similarity) (PubMed:9537324).
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:25060689, PubMed:12504075, PubMed:8805376).
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. Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus. Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T -ells. Leptin increases Th1 and suppresses Th2 cytokine production (By similarity).
Isoform A
May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3.
Isoform E
Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.

AngiogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Bone growthISS:UniProtKB
Cell surface receptor signaling pathwayManual Assertion Based On ExperimentTAS:ProtInc
Cholesterol metabolic processIEA:Ensembl
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Energy homeostasisISS:UniProtKB
Energy reserve metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Glial cell proliferationIEA:Ensembl
Glucose homeostasisISS:UniProtKB
Glycogen metabolic processIEA:Ensembl
Leptin-mediated signaling pathwayManual Assertion Based On ExperimentIDA:ARUK-UCL
Multicellular organism developmentManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of autophagyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of gluconeogenesisIEA:Ensembl
Negative regulation of hydrolase activityIEA:Ensembl
PhagocytosisIEA:Ensembl
Positive regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:ARUK-UCL
Regulation of bone remodelingISS:UniProtKB
Regulation of feeding behaviorISS:UniProtKB
Regulation of transportManual Assertion Based On ExperimentIDA:ARUK-UCL
Response to leptinISS:UniProtKB
Sexual reproductionISS:UniProtKB
T cell differentiationISS:UniProtKB
Transport across blood-brain barrier2 PublicationsNAS:ARUK-UCL

Cell membrane
Basolateral cell membrane
Isoform E:
Secreted

Leptin receptor deficiency (LEPRD):
A rare disease characterized by normal levels of serum leptin, hyperphagia and severe obesity from an early age. Additional features include alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism.

Extracellular: 22-839
Helical: 840-862
Cytoplasmic: 863-1165

On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-986 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-1141 is required for STAT3 binding/activation. Phosphorylation of Tyr-1079 has a more accessory role.