P41159 · LEP_HUMAN

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).

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentextracellular region
Cellular Componentextracellular space
Molecular FunctionDNA binding
Molecular Functionhormone activity
Molecular Functionleptin receptor binding
Molecular Functionpeptide hormone receptor binding
Biological Processactivation of protein kinase C activity
Biological Processadipose tissue development
Biological Processadult feeding behavior
Biological Processangiogenesis
Biological Processaorta development
Biological Processbile acid metabolic process
Biological Processbone growth
Biological Processbone mineralization involved in bone maturation
Biological Processcardiac muscle hypertrophy
Biological Processcellular response to insulin stimulus
Biological Processcellular response to L-ascorbic acid
Biological Processcellular response to leptin stimulus
Biological Processcellular response to retinoic acid
Biological Processcentral nervous system neuron development
Biological Processcholesterol metabolic process
Biological Processcircadian rhythm
Biological Processdetermination of adult lifespan
Biological Processeating behavior
Biological Processelastin metabolic process
Biological Processenergy homeostasis
Biological Processenergy reserve metabolic process
Biological Processfatty acid beta-oxidation
Biological Processfemale pregnancy
Biological Processglucose homeostasis
Biological Processglucose metabolic process
Biological Processglycerol biosynthetic process
Biological Processhormone metabolic process
Biological Processinsulin secretion
Biological Processintestinal absorption
Biological Processintracellular signal transduction
Biological Processleptin-mediated signaling pathway
Biological Processleukocyte tethering or rolling
Biological Processlipid metabolic process
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of appetite
Biological Processnegative regulation of appetite by leptin-mediated signaling pathway
Biological Processnegative regulation of autophagy
Biological Processnegative regulation of cartilage development
Biological Processnegative regulation of glucagon secretion
Biological Processnegative regulation of glucose import
Biological Processnegative regulation of glutamine transport
Biological Processnegative regulation of lipid storage
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processnegative regulation of vasoconstriction
Biological Processovulation from ovarian follicle
Biological Processphagocytosis
Biological Processplacenta development
Biological Processpositive regulation of cold-induced thermogenesis
Biological Processpositive regulation of developmental growth
Biological Processpositive regulation of fat cell apoptotic process
Biological Processpositive regulation of follicle-stimulating hormone secretion
Biological Processpositive regulation of hepatic stellate cell activation
Biological Processpositive regulation of insulin receptor signaling pathway
Biological Processpositive regulation of interleukin-12 production
Biological Processpositive regulation of interleukin-6 production
Biological Processpositive regulation of interleukin-8 production
Biological Processpositive regulation of luteinizing hormone secretion
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of monoatomic ion transport
Biological Processpositive regulation of p38MAPK cascade
Biological Processpositive regulation of peroxisome proliferator activated receptor signaling pathway
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processpositive regulation of protein import into nucleus
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of reactive oxygen species metabolic process
Biological Processpositive regulation of receptor signaling pathway via JAK-STAT
Biological Processpositive regulation of T cell proliferation
Biological Processpositive regulation of TOR signaling
Biological Processpositive regulation of tumor necrosis factor production
Biological Processpositive regulation of tyrosine phosphorylation of STAT protein
Biological Processprostaglandin secretion
Biological Processregulation of angiogenesis
Biological Processregulation of blood pressure
Biological Processregulation of bone remodeling
Biological Processregulation of brown fat cell differentiation
Biological Processregulation of cell cycle
Biological Processregulation of cytokine production involved in inflammatory response
Biological Processregulation of endothelial cell proliferation
Biological Processregulation of gluconeogenesis
Biological Processregulation of insulin secretion
Biological Processregulation of intestinal cholesterol absorption
Biological Processregulation of lipoprotein lipid oxidation
Biological Processregulation of natural killer cell activation
Biological Processregulation of natural killer cell mediated cytotoxicity
Biological Processregulation of natural killer cell proliferation
Biological Processregulation of nitric-oxide synthase activity
Biological Processregulation of steroid biosynthetic process
Biological Processresponse to activity
Biological Processresponse to dietary excess
Biological Processresponse to estradiol
Biological Processresponse to ethanol
Biological Processresponse to hypoxia
Biological Processresponse to insulin
Biological Processresponse to vitamin E
Biological Processsexual reproduction
Biological ProcessT cell differentiation

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Leptin
  • Alternative names
    • Obese protein
    • Obesity factor

Gene names

    • Name
      LEP
    • Synonyms
      OB
      , OBS

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P41159
  • Secondary accessions
    • O15158
    • Q56A88

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Involvement in disease

Leptin deficiency (LEPD)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.
  • See also
    MIM:614962
Natural variants in LEPD
Variant IDPosition(s)ChangeDescription
VAR_075144100D>Yin LEPD; no effect on secretion; does not bind or activate LEPR; dbSNP:rs724159998
VAR_008094105R>Win LEPD; dbSNP:rs104894023

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_00419649
Natural variantVAR_00419794in dbSNP:rs17151919
Natural variantVAR_075144100in LEPD; no effect on secretion; does not bind or activate LEPR; dbSNP:rs724159998
Natural variantVAR_008094105in LEPD; dbSNP:rs104894023
Natural variantVAR_011955110in dbSNP:rs1800564

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.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for signal, chain, disulfide bond.

TypeIDPosition(s)Description
Signal1-21
ChainPRO_000001768522-167Leptin
Disulfide bond117↔167

Keywords

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).

Induction

Induced by secretin.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with SIGLEC6.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P41159HSF2BP O750313EBI-12994693, EBI-7116203
BINARY P41159LEPR P483573EBI-12994693, EBI-518596

Protein-protein interaction databases

Miscellaneous

Family & Domains

Sequence similarities

Belongs to the leptin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    167
  • Mass (Da)
    18,641
  • Last updated
    1995-02-01 v1
  • Checksum
    C91A121E92D37B69
MHWGTLCGFLWLWPYLFYVQAVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict96in Ref. 8; AAB63507

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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