Protein: Leptin (Obese protein) (Obesity factor) (P41159)
Organism: Homo sapiens (Human)
Function: Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, 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. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity (By similarity). In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides (By similarity). In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption. Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways (By similarity). May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression. Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells. Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38. In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses (By similarity). Increases CD4(+)CD25(-) T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.
Subcellular location: Secreted {ECO:0000305|PubMed:25232147}.
Sequence: MHWGTLCGFLWLWPYLFYVQAVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC
InterPro domains: - IPR000065: Leptin (family) [1-167]
- IPR009079: Four-helical cytokine-like, core (homologous_superfamily) [22-167]
Interaction partners: - Leptin receptor
- Pro-neuropeptide Y
- Adiponectin
- Appetite-regulating hormone
- Pro-opiomelanocortin
- Insulin
- Prolactin
- Pro-glucagon
- Agouti-related protein
- Ciliary neurotrophic factor
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0048519 (negative regulation of biological process), GO:0023056 (positive regulation of signaling), GO:0019222 (regulation of metabolic process), GO:0048584 (positive regulation of response to stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0048523 (negative regulation of cellular process), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0009892 (negative regulation of metabolic process), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0009894 (regulation of catabolic process), GO:0009967 (positive regulation of signal transduction), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0042127 (regulation of cell population proliferation), GO:0010646 (regulation of cell communication), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0008285 (negative regulation of cell population proliferation), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0010647 (positive regulation of cell communication), GO:0009895 (negative regulation of catabolic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0042177 (negative regulation of protein catabolic process), GO:0042176 (regulation of protein catabolic process), GO:0051246 (regulation of protein metabolic process), GO:0031330 (negative regulation of cellular catabolic process), GO:0051248 (negative regulation of protein metabolic process), GO:0010506 (regulation of autophagy), GO:1902533 (positive regulation of intracellular signal transduction), GO:0031329 (regulation of cellular catabolic process), GO:1902531 (regulation of intracellular signal transduction), GO:0043408 (regulation of MAPK cascade), GO:0051896 (regulation of protein kinase B signaling), GO:0030162 (regulation of proteolysis), GO:0043410 (positive regulation of MAPK cascade), GO:2000059 (negative regulation of ubiquitin-dependent protein catabolic process), GO:1901799 (negative regulation of proteasomal protein catabolic process), GO:0061136 (regulation of proteasomal protein catabolic process), GO:0045861 (negative regulation of proteolysis), GO:2000058 (regulation of ubiquitin-dependent protein catabolic process), GO:1903050 (regulation of proteolysis involved in protein catabolic process), GO:0032434 (regulation of proteasomal ubiquitin-dependent protein catabolic process), GO:0032435 (negative regulation of proteasomal ubiquitin-dependent protein catabolic process), GO:1903051 (negative regulation of proteolysis involved in protein catabolic process), GO:0070372 (regulation of ERK1 and ERK2 cascade)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0005794 (Golgi apparatus), GO:0043233 (organelle lumen), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0031904 (endosome lumen), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0070013 (intracellular organelle lumen), GO:0097708 (intracellular vesicle)