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Protein

Leptin

Gene

Lep

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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).IKR:HMP:10 Publications

GO - Molecular functioni

GO - Biological processi

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 – 21IEP:Add BLAST21
ChainiPRO_000001768722 – 167LeptinAdd BLAST146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi117 ↔ 167HMP:

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

BioGridi201138. 4 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.IKR:

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: October 25, 2017
This is version 153 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families