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Protein

Leptin

Gene

Lep

Organism
Mus musculus (Mouse)
Status
Unreviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. 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 annotation

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
LeptinUniRule annotation
Alternative name(s):
Obesity factorUniRule annotation
Gene namesi
Name:LepImported
ORF Names:mCG_9137Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Organism-specific databases

MGIiMGI:104663. Lep.

Subcellular locationi

  • Secreted UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

SecretedUniRule annotation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_500878080022 – 167LeptinSequence analysisAdd BLAST146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi117 ↔ 167UniRule annotation

Keywords - PTMi

Disulfide bondUniRule annotation

Expressioni

Gene expression databases

BgeeiENSMUSG00000059201.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000067046.

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.UniRule annotation

Keywords - Domaini

SignalSequence analysis

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
HOVERGENiHBG007860.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG091G0Y82.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000065. Leptin.
[Graphical view]
PANTHERiPTHR11724. PTHR11724. 1 hit.
PfamiPF02024. Leptin. 1 hit.
[Graphical view]
PIRSFiPIRSF001837. Leptin. 1 hit.
PRINTSiPR00495. LEPTIN.
ProDomiPD005698. Leptin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF47266. SSF47266. 1 hit.

Sequencei

Sequence statusi: Complete.

Q544U0-1 [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:May 24, 2005 - v1
Checksum:iD6783E6C76FD7116
GO

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.
CH466533 Genomic DNA. Translation: EDL13794.1.
CH466533 Genomic DNA. Translation: EDL13795.1.
RefSeqiNP_032519.1. NM_008493.3.
UniGeneiMm.277072.

Genome annotation databases

GeneIDi16846.
KEGGimmu:16846.

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.
CH466533 Genomic DNA. Translation: EDL13794.1.
CH466533 Genomic DNA. Translation: EDL13795.1.
RefSeqiNP_032519.1. NM_008493.3.
UniGeneiMm.277072.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000067046.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi16846.
KEGGimmu:16846.

Organism-specific databases

CTDi3952.
MGIiMGI:104663. Lep.

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
HOVERGENiHBG007860.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG091G0Y82.

Miscellaneous databases

SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000059201.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000065. Leptin.
[Graphical view]
PANTHERiPTHR11724. PTHR11724. 1 hit.
PfamiPF02024. Leptin. 1 hit.
[Graphical view]
PIRSFiPIRSF001837. Leptin. 1 hit.
PRINTSiPR00495. LEPTIN.
ProDomiPD005698. Leptin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF47266. SSF47266. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiQ544U0_MOUSE
AccessioniPrimary (citable) accession number: Q544U0
Entry historyi
Integrated into UniProtKB/TrEMBL: May 24, 2005
Last sequence update: May 24, 2005
Last modified: November 30, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.