UniProtKB - Q544U0 (Q544U0_MOUSE)
Leptin
Lep
Functioni
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. 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. 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. 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. Increases CD4+CD25- T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.
UniRule annotationGO - Molecular functioni
- hormone activity Source: Ensembl
- leptin receptor binding Source: Ensembl
- peptide hormone receptor binding Source: Ensembl
GO - Biological processi
- activation of protein kinase C activity Source: Ensembl
- angiogenesis Source: Ensembl
- bone mineralization involved in bone maturation Source: Ensembl
- cardiac muscle hypertrophy Source: Ensembl
- cellular response to L-ascorbic acid Source: Ensembl
- cellular response to retinoic acid Source: Ensembl
- circadian rhythm Source: Ensembl
- energy reserve metabolic process Source: Ensembl
- fatty acid catabolic process Source: Ensembl
- female pregnancy Source: Ensembl
- glycerol biosynthetic process Source: Ensembl
- intestinal absorption Source: Ensembl
- intracellular signal transduction Source: Ensembl
- leukocyte tethering or rolling Source: Ensembl
- negative regulation of apoptotic process Source: Ensembl
- negative regulation of appetite by leptin-mediated signaling pathway Source: Ensembl
- negative regulation of autophagy Source: Ensembl
- negative regulation of cartilage development Source: Ensembl
- negative regulation of glucose import Source: Ensembl
- negative regulation of glutamine transport Source: Ensembl
- negative regulation of lipid storage Source: Ensembl
- negative regulation of vasoconstriction Source: Ensembl
- ovulation from ovarian follicle Source: Ensembl
- phagocytosis Source: Ensembl
- placenta development Source: Ensembl
- positive regulation of developmental growth Source: Ensembl
- positive regulation of fat cell apoptotic process Source: Ensembl
- positive regulation of follicle-stimulating hormone secretion Source: Ensembl
- positive regulation of hepatic stellate cell activation Source: Ensembl
- positive regulation of insulin receptor signaling pathway Source: Ensembl
- positive regulation of interleukin-6 production Source: Ensembl
- positive regulation of interleukin-8 production Source: Ensembl
- positive regulation of ion transport Source: Ensembl
- positive regulation of luteinizing hormone secretion Source: Ensembl
- positive regulation of p38MAPK cascade Source: Ensembl
- positive regulation of peroxisome proliferator activated receptor signaling pathway Source: Ensembl
- positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
- positive regulation of reactive oxygen species metabolic process Source: Ensembl
- positive regulation of receptor signaling pathway via JAK-STAT Source: Ensembl
- positive regulation of T cell proliferation Source: Ensembl
- positive regulation of TOR signaling Source: Ensembl
- positive regulation of tyrosine phosphorylation of STAT protein Source: Ensembl
- prostaglandin secretion Source: Ensembl
- regulation of angiogenesis Source: Ensembl
- regulation of blood pressure Source: Ensembl
- regulation of cell cycle Source: Ensembl
- regulation of cytokine production involved in inflammatory response Source: Ensembl
- regulation of endothelial cell proliferation Source: Ensembl
- regulation of lipoprotein lipid oxidation Source: Ensembl
- regulation of natural killer cell mediated cytotoxicity Source: Ensembl
- regulation of natural killer cell proliferation Source: Ensembl
- regulation of nitric-oxide synthase activity Source: Ensembl
- response to activity Source: Ensembl
- response to dietary excess Source: Ensembl
- response to estradiol Source: Ensembl
- response to ethanol Source: Ensembl
- response to hypoxia Source: Ensembl
- response to vitamin E Source: Ensembl
Names & Taxonomyi
| Protein namesi | Recommended name: LeptinUniRule annotationARBA annotationAlternative name(s): Obesity factorUniRule annotationARBA annotation |
| Gene namesi | Name:LepImported |
| Organismi | Mus musculus (Mouse)Imported |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Organism-specific databases
| MGIi | MGI:104663, Lep |
Subcellular locationi
Extracellular region or secreted
- Secreted UniRule annotation
Cytosol
- cytosol Source: Ensembl
Extracellular region or secreted
- extracellular space Source: Ensembl
Keywords - Cellular componenti
SecretedUniRule annotationPTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
| ChainiPRO_5014309631 | 22 – 167 | LeptinSequence analysisAdd BLAST | 146 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Disulfide bondi | 117 ↔ 167 | UniRule annotation |
Keywords - PTMi
Disulfide bondUniRule annotationExpressioni
Gene expression databases
| Bgeei | ENSMUSG00000059201, Expressed in white adipose tissue and 77 other tissues |
| ExpressionAtlasi | Q544U0, baseline and differential |
Interactioni
GO - Molecular functioni
- hormone activity Source: Ensembl
- leptin receptor binding Source: Ensembl
- peptide hormone receptor binding Source: Ensembl
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalSequence analysisPhylogenomic databases
| HOGENOMi | CLU_132715_0_0_1 |
| OMAi | MRCGPLC |
| OrthoDBi | 1350528at2759 |
Family and domain databases
| InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR000065, Leptin |
| PANTHERi | PTHR11724, PTHR11724, 1 hit |
| Pfami | View protein in Pfam PF02024, Leptin, 1 hit |
| PIRSFi | PIRSF001837, Leptin, 1 hit |
| PRINTSi | PR00495, LEPTIN |
| SUPFAMi | SSF47266, SSF47266, 1 hit |
Sequencei
Sequence statusi: Complete.
10 20 30 40 50
MCWRPLCRFL WLWSYLSYVQ AVPIQKVQDD TKTLIKTIVT RINDISHTQS
60 70 80 90 100
VSAKQRVTGL DFIPGLHPIL SLSKMDQTLA VYQQVLTSLP SQNVLQIAND
110 120 130 140 150
LENLRDLLHL LAFSKSCSLP QTSGLQKPES LDGVLEASLY STEVVALSRL
160
QGSLQDILQQ LDVSPEC
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC125245 mRNA Translation: AAI25246.1 FJ374142 mRNA Translation: ACJ09173.1 AK030984 mRNA Translation: BAC27202.1 AK142589 mRNA Translation: BAE25117.1 |
| RefSeqi | NP_032519.1, NM_008493.3 |
Genome annotation databases
| GeneIDi | 16846 |
| KEGGi | mmu:16846 |
Similar proteinsi
Cross-referencesi
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC125245 mRNA Translation: AAI25246.1 FJ374142 mRNA Translation: ACJ09173.1 AK030984 mRNA Translation: BAC27202.1 AK142589 mRNA Translation: BAE25117.1 |
| RefSeqi | NP_032519.1, NM_008493.3 |
3D structure databases
| SMRi | Q544U0 |
| ModBasei | Search... |
Protocols and materials databases
| Antibodypediai | 3389, 1442 antibodies |
| DNASUi | 16846 |
Genome annotation databases
| GeneIDi | 16846 |
| KEGGi | mmu:16846 |
Organism-specific databases
| CTDi | 3952 |
| MGIi | MGI:104663, Lep |
Phylogenomic databases
| HOGENOMi | CLU_132715_0_0_1 |
| OMAi | MRCGPLC |
| OrthoDBi | 1350528at2759 |
Miscellaneous databases
| BioGRID-ORCSi | 16846, 0 hits in 52 CRISPR screens |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSMUSG00000059201, Expressed in white adipose tissue and 77 other tissues |
| ExpressionAtlasi | Q544U0, baseline and differential |
Family and domain databases
| InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR000065, Leptin |
| PANTHERi | PTHR11724, PTHR11724, 1 hit |
| Pfami | View protein in Pfam PF02024, Leptin, 1 hit |
| PIRSFi | PIRSF001837, Leptin, 1 hit |
| PRINTSi | PR00495, LEPTIN |
| SUPFAMi | SSF47266, SSF47266, 1 hit |
| MobiDBi | Search... |
Entry informationi
| Entry namei | Q544U0_MOUSE | |
| Accessioni | Q544U0Primary (citable) accession number: Q544U0 | |
| Entry historyi | Integrated into UniProtKB/TrEMBL: | May 24, 2005 |
| Last sequence update: | May 24, 2005 | |
| Last modified: | June 2, 2021 | |
| This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Unreviewed (UniProtKB/TrEMBL) | |
