Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Leptin

Gene

LEP

Organism
Homo sapiens (Human)
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:17344214, PubMed:15899045, 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:8589726, PubMed:11460888, PubMed:19688109, PubMed:24340098, PubMed:25060689). 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).By similarity2 Publications9 Publications

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-2586552 Signaling by Leptin
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-422085 Synthesis, secretion, and deacylation of Ghrelin
SignaLinkiP41159
SIGNORiP41159

Names & Taxonomyi

Protein namesi
Recommended name:
LeptinImported
Alternative name(s):
Obese protein
Obesity factor
Gene namesi
Name:LEPImported
Synonyms:OBImported, OBSImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000174697.4
HGNCiHGNC:6553 LEP
MIMi164160 gene
neXtProtiNX_P41159

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

Leptin deficiency (LEPD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.
See also OMIM:614962
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075144100D → Y in LEPD; no effect on secretion; does not bind or activate LEPR. 1 PublicationCorresponds to variant dbSNP:rs724159998EnsemblClinVar.1
Natural variantiVAR_008094105R → W in LEPD. 1 PublicationCorresponds to variant dbSNP:rs104894023EnsemblClinVar.1

Keywords - Diseasei

Diabetes mellitus, Disease mutation, Obesity

Organism-specific databases

DisGeNETi3952
MalaCardsiLEP
MIMi614962 phenotype
OpenTargetsiENSG00000174697
Orphaneti66628 Obesity due to congenital leptin deficiency
PharmGKBiPA228

Polymorphism and mutation databases

BioMutaiLEP

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001768522 – 167LeptinAdd BLAST146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi117 ↔ 167

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP41159
PeptideAtlasiP41159
PRIDEiP41159

PTM databases

iPTMnetiP41159
PhosphoSitePlusiP41159

Expressioni

Tissue specificityi

Adipose tissue is the main source of leptin it is also produced by other peripheral tissues such as the skeletal muscle (PubMed:7789654, PubMed:16052473, PubMed:12448771). 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).4 Publications

Inductioni

Induced by secretin.1 Publication

Gene expression databases

BgeeiENSG00000174697
CleanExiHS_LEP
ExpressionAtlasiP41159 baseline and differential
GenevisibleiP41159 HS

Organism-specific databases

HPAiCAB010490

Interactioni

Subunit structurei

Interacts with SIGLEC6.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110143, 5 interactors
DIPiDIP-6116N
IntActiP41159, 2 interactors
STRINGi9606.ENSP00000312652

Structurei

Secondary structure

1167
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi25 – 44Combined sources20
Helixi72 – 87Combined sources16
Helixi92 – 114Combined sources23
Helixi128 – 131Combined sources4
Helixi132 – 135Combined sources4
Helixi142 – 160Combined sources19
Helixi161 – 163Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AX8X-ray2.40A22-167[»]
ProteinModelPortaliP41159
SMRiP41159
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41159

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVT0 Eukaryota
ENOG410Y7NT LUCA
GeneTreeiENSGT00390000011772
HOGENOMiHOG000252923
HOVERGENiHBG007860
InParanoidiP41159
KOiK05424
OMAiQISNDLE
OrthoDBiEOG091G0Y82
PhylomeDBiP41159
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.

P41159-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHWGTLCGFL WLWPYLFYVQ AVPIQKVQDD TKTLIKTIVT RINDISHTQS
60 70 80 90 100
VSSKQKVTGL DFIPGLHPIL TLSKMDQTLA VYQQILTSMP SRNVIQISND
110 120 130 140 150
LENLRDLLHV LAFSKSCHLP WASGLETLDS LGGVLEASGY STEVVALSRL
160
QGSLQDMLWQ LDLSPGC
Length:167
Mass (Da):18,641
Last modified:February 1, 1995 - v1
Checksum:iC91A121E92D37B69
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96Q → R in AAB63507 (Ref. 7) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00419649Missing . 1
Natural variantiVAR_00419794V → M2 PublicationsCorresponds to variant dbSNP:rs17151919EnsemblClinVar.1
Natural variantiVAR_075144100D → Y in LEPD; no effect on secretion; does not bind or activate LEPR. 1 PublicationCorresponds to variant dbSNP:rs724159998EnsemblClinVar.1
Natural variantiVAR_008094105R → W in LEPD. 1 PublicationCorresponds to variant dbSNP:rs104894023EnsemblClinVar.1
Natural variantiVAR_011955110V → M. Corresponds to variant dbSNP:rs1800564Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U18915 mRNA Translation: AAA60470.1
D49487 mRNA Translation: BAA08448.1
U43653 mRNA Translation: AAC50400.1
U43415 Genomic DNA Translation: AAC31660.1
D63710 Genomic DNA Translation: BAA09839.1
D63519 Genomic DNA Translation: BAA09787.1
AF008123 mRNA Translation: AAB63507.1
AY996373 Genomic DNA Translation: AAX81413.1
BC060830 mRNA Translation: AAH60830.1
BC069452 mRNA Translation: AAH69452.1
BC069527 mRNA Translation: AAH69527.1
CCDSiCCDS5800.1
PIRiA38952 LTHU
I53166
RefSeqiNP_000221.1, NM_000230.2
XP_005250397.1, XM_005250340.4
UniGeneiHs.194236

Genome annotation databases

EnsembliENST00000308868; ENSP00000312652; ENSG00000174697
GeneIDi3952
KEGGihsa:3952
UCSCiuc003vml.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLEP_HUMAN
AccessioniPrimary (citable) accession number: P41159
Secondary accession number(s): O15158, Q56A88
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: May 23, 2018
This is version 177 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health