P41159 · LEP_HUMAN
- ProteinLeptin
- GeneLEP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids167 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PubMed:15899045, PubMed:17344214, PubMed:19688109).
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) (PubMed:11460888, PubMed:19688109, PubMed:24340098, PubMed:25060689, PubMed:8589726).
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 (PubMed:24340098).
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) (PubMed:17344214).
May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression (PubMed:18242580).
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) (PubMed:11460888).
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 (PubMed:12504075).
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 (PubMed:15899045, PubMed:19688109).
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 (PubMed:25060689).
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) (PubMed:11460888, PubMed:19688109, PubMed:24340098, PubMed:25060689, PubMed:8589726).
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 (PubMed:24340098).
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) (PubMed:17344214).
May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression (PubMed:18242580).
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) (PubMed:11460888).
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 (PubMed:12504075).
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 (PubMed:15899045, PubMed:19688109).
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 (PubMed:25060689).
GO annotations
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLeptin
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP41159
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Leptin deficiency (LEPD)
- Note
- DescriptionA rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.
- See alsoMIM:614962
Natural variants in LEPD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_075144 | 100 | D>Y | in LEPD; no effect on secretion; does not bind or activate LEPR; dbSNP:rs724159998 | |
VAR_008094 | 105 | R>W | in LEPD; dbSNP:rs104894023 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_004196 | 49 | ||||
Sequence: Missing | ||||||
Natural variant | VAR_004197 | 94 | in dbSNP:rs17151919 | |||
Sequence: V → M | ||||||
Natural variant | VAR_075144 | 100 | in LEPD; no effect on secretion; does not bind or activate LEPR; dbSNP:rs724159998 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_008094 | 105 | in LEPD; dbSNP:rs104894023 | |||
Sequence: R → W | ||||||
Natural variant | VAR_011955 | 110 | in dbSNP:rs1800564 | |||
Sequence: V → M |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 169 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MHWGTLCGFLWLWPYLFYVQA | ||||||
Chain | PRO_0000017685 | 22-167 | Leptin | |||
Sequence: VPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC | ||||||
Disulfide bond | 117↔167 | |||||
Sequence: CHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Adipose tissue is the main source of leptin. It is also produced by other peripheral tissues such as the skeletal muscle (PubMed:12448771, PubMed:16052473, PubMed:7789654).
Expressed by intercalated and striated tracts of submandibular and parotid salivary gland intralobular ducts (PubMed:12448771).
Detected by fundic epithelium of the gastric mucosa (PubMed:10896907).
Secreted into blood and gastric juice (PubMed:10896907).
Expressed by intercalated and striated tracts of submandibular and parotid salivary gland intralobular ducts (PubMed:12448771).
Detected by fundic epithelium of the gastric mucosa (PubMed:10896907).
Secreted into blood and gastric juice (PubMed:10896907).
Induction
Induced by secretin.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with SIGLEC6.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P41159 | HSF2BP O75031 | 3 | EBI-12994693, EBI-7116203 | |
BINARY | P41159 | LEPR P48357 | 3 | EBI-12994693, EBI-518596 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length167
- Mass (Da)18,641
- Last updated1995-02-01 v1
- ChecksumC91A121E92D37B69
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 96 | in Ref. 8; AAB63507 | ||||
Sequence: Q → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U18915 EMBL· GenBank· DDBJ | AAA60470.1 EMBL· GenBank· DDBJ | mRNA | ||
D49487 EMBL· GenBank· DDBJ | BAA08448.1 EMBL· GenBank· DDBJ | mRNA | ||
U43653 EMBL· GenBank· DDBJ | AAC50400.1 EMBL· GenBank· DDBJ | mRNA | ||
U43415 EMBL· GenBank· DDBJ | AAC31660.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D63710 EMBL· GenBank· DDBJ | BAA09839.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D63519 EMBL· GenBank· DDBJ | BAA09787.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF008123 EMBL· GenBank· DDBJ | AAB63507.1 EMBL· GenBank· DDBJ | mRNA | ||
AY996373 EMBL· GenBank· DDBJ | AAX81413.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC060830 EMBL· GenBank· DDBJ | AAH60830.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069452 EMBL· GenBank· DDBJ | AAH69452.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069527 EMBL· GenBank· DDBJ | AAH69527.1 EMBL· GenBank· DDBJ | mRNA |