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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:12504075, PubMed:25060689, 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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P48356"}],"value":"May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. 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Isoform B and isoform A are expressed by NK cells (at protein level) (PubMed:12504075)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"value":"The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs"}],"commentType":"DOMAIN"},{"texts":[{"value":"The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding"}],"commentType":"DOMAIN"},{"texts":[{"value":"The box 1 motif is required for JAK interaction and/or activation"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P48356"}],"value":"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. 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