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Protein

Leptin

Gene

Lep

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 (PubMed:15899045, PubMed:16825198, PubMed:11373681, PubMed:12594516, PubMed:20620997). 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:8589726, PubMed:10660043, PubMed:25383904, PubMed:25060689, PubMed:9732873, PubMed:12594516). 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) (PubMed:20620997, PubMed:11373681). 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) (PubMed:16825198, PubMed:20620997). May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression (By similarity). 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:16825198). 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 (Probable). 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). In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses (By similarity). Increases CD4+CD25- T cells proliferation and reduces autophagy during TCR (T cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation (PubMed:25060689).By similarity2 Publications10 Publications

GO - Molecular functioni

GO - Biological processi

  • activation of protein kinase C activity Source: UniProtKB
  • adipose tissue development Source: MGI
  • adult feeding behavior Source: HGNC
  • angiogenesis Source: MGI
  • bile acid metabolic process Source: MGI
  • bone growth Source: UniProtKB
  • bone mineralization involved in bone maturation Source: Ensembl
  • cardiac muscle hypertrophy Source: Ensembl
  • cellular response to L-ascorbic acid Source: Ensembl
  • cellular response to leptin stimulus Source: UniProtKB
  • cellular response to retinoic acid Source: Ensembl
  • central nervous system neuron development Source: MGI
  • cholesterol metabolic process Source: MGI
  • circadian rhythm Source: Ensembl
  • eating behavior Source: MGI
  • energy reserve metabolic process Source: GO_Central
  • fatty acid beta-oxidation Source: MGI
  • female pregnancy Source: Ensembl
  • glucose homeostasis Source: MGI
  • glucose metabolic process Source: MGI
  • glycerol biosynthetic process Source: Ensembl
  • hormone metabolic process Source: MGI
  • insulin secretion Source: MGI
  • interleukin-12 production Source: UniProtKB
  • interleukin-6 production Source: UniProtKB
  • interleukin-6 secretion Source: UniProtKB
  • interleukin-8 secretion Source: UniProtKB
  • intestinal absorption Source: UniProtKB
  • leptin-mediated signaling pathway Source: UniProtKB
  • leukocyte tethering or rolling Source: Ensembl
  • lipid metabolic process Source: MGI
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of appetite Source: HGNC
  • negative regulation of appetite by leptin-mediated signaling pathway Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of cartilage development Source: Ensembl
  • negative regulation of glucagon secretion Source: BHF-UCL
  • negative regulation of glucose import Source: UniProtKB
  • negative regulation of glutamine transport Source: Ensembl
  • negative regulation of lipid storage Source: Ensembl
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • negative regulation of vasoconstriction Source: Ensembl
  • ovulation from ovarian follicle Source: Ensembl
  • phagocytosis Source: UniProtKB
  • placenta development Source: MGI
  • positive regulation of developmental growth Source: MGI
  • 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 ion transport Source: Ensembl
  • positive regulation of JAK-STAT cascade Source: UniProtKB
  • positive regulation of luteinizing hormone secretion Source: Ensembl
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of p38MAPK cascade Source: UniProtKB
  • positive regulation of peroxisome proliferator activated receptor signaling pathway Source: Ensembl
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of protein import into nucleus Source: BHF-UCL
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: Ensembl
  • positive regulation of STAT protein import into nucleus Source: BHF-UCL
  • positive regulation of T cell proliferation Source: MGI
  • positive regulation of TOR signaling Source: MGI
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of STAT protein Source: Ensembl
  • prostaglandin secretion Source: UniProtKB
  • regulation of angiogenesis Source: UniProtKB
  • regulation of blood pressure Source: Ensembl
  • regulation of bone remodeling Source: UniProtKB
  • regulation of brown fat cell differentiation Source: UniProtKB
  • regulation of cell cycle Source: UniProtKB
  • regulation of cytokine production involved in inflammatory response Source: UniProtKB
  • regulation of endothelial cell proliferation Source: UniProtKB
  • regulation of fat cell differentiation Source: MGI
  • regulation of gluconeogenesis Source: MGI
  • regulation of insulin secretion Source: MGI
  • regulation of intestinal cholesterol absorption Source: MGI
  • regulation of lipoprotein lipid oxidation Source: Ensembl
  • regulation of metabolic process Source: MGI
  • regulation of natural killer cell activation Source: UniProtKB
  • regulation of natural killer cell mediated cytotoxicity Source: UniProtKB
  • regulation of natural killer cell proliferation Source: UniProtKB
  • regulation of nitric-oxide synthase activity Source: UniProtKB
  • regulation of protein localization to nucleus Source: MGI
  • regulation of protein phosphorylation Source: BHF-UCL
  • regulation of steroid biosynthetic process Source: MGI
  • response to activity Source: Ensembl
  • response to dietary excess Source: MGI
  • response to estradiol Source: Ensembl
  • response to ethanol Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to insulin Source: MGI
  • response to vitamin E Source: Ensembl
  • sexual reproduction Source: UniProtKB
  • T cell differentiation Source: UniProtKB
  • tyrosine phosphorylation of STAT protein Source: BHF-UCL

Enzyme and pathway databases

ReactomeiR-MMU-2586551 Signaling by Leptin
R-MMU-2586552 Signaling by Leptin
R-MMU-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-MMU-422085 Synthesis, secretion, and deacylation of Ghrelin

Names & Taxonomyi

Protein namesi
Recommended name:
Leptin
Alternative name(s):
Obesity factor
Gene namesi
Name:Lep
Synonyms:Ob
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:104663 Lep

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Defects in Lep are the cause of profound obesity and type II diabetes.

Disruption phenotypei

Mutants are severely obese and sterile (PubMed:8589726). Animals have an increased bone formation leading to high bone mass (PubMed:10660043). Have impaired T-cell immunity, Th2 responses are favoured in mutants (PubMed:9732873). CD4+CD25- T-cells of mutant mice show high levels of autophagy (PubMed:25060689).4 Publications

Keywords - Diseasei

Diabetes mellitus, Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001768722 – 167LeptinAdd BLAST146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi117 ↔ 167By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP41160
PRIDEiP41160

PTM databases

PhosphoSitePlusiP41160

Expressioni

Gene expression databases

BgeeiENSMUSG00000059201
CleanExiMM_LEP
ExpressionAtlasiP41160 baseline and differential
GenevisibleiP41160 MM

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
LeprP483566EBI-16108810,EBI-2257257

GO - Molecular functioni

Protein-protein interaction databases

BioGridi2011384 interactors.
CORUMiP41160
DIPiDIP-60999N
IntActiP41160 1 interactor.
STRINGi10090.ENSMUSP00000067046

Structurei

3D structure databases

ProteinModelPortaliP41160
SMRiP41160
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVT0 Eukaryota
ENOG410Y7NT LUCA
GeneTreeiENSGT00390000011772
HOGENOMiHOG000252923
HOVERGENiHBG007860
InParanoidiP41160
KOiK05424
OMAiQISNDLE
OrthoDBiEOG091G0Y82
PhylomeDBiP41160
TreeFamiTF105086

Family and domain databases

InterProiView protein in InterPro
IPR009079 4_helix_cytokine-like_core
IPR000065 Leptin
PANTHERiPTHR11724 PTHR11724, 1 hit
PfamiView protein in Pfam
PF02024 Leptin, 1 hit
PIRSFiPIRSF001837 Leptin, 1 hit
PRINTSiPR00495 LEPTIN
ProDomiView protein in ProDom or Entries sharing at least one domain
PD005698 Leptin, 1 hit
SUPFAMiSSF47266 SSF47266, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P41160-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:167
Mass (Da):18,709
Last modified:February 1, 1995 - v1
Checksum:iD6783E6C76FD7116
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti49Missing in 30% the clones. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U18812 mRNA Translation: AAA64564.1
U22421 Genomic DNA Translation: AAA64213.1
CCDSiCCDS19955.1
PIRiS50863 LTMS
RefSeqiNP_032519.1, NM_008493.3
UniGeneiMm.277072

Genome annotation databases

EnsembliENSMUST00000069789; ENSMUSP00000067046; ENSMUSG00000059201
GeneIDi16846
KEGGimmu:16846
UCSCiuc009bcv.1 mouse

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLEP_MOUSE
AccessioniPrimary (citable) accession number: P41160
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: March 28, 2018
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome