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Protein

Leptin

Gene

Lep

Organism
Rattus norvegicus (Rat)
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 (By similarity) (PubMed:11677594). 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:10482243, PubMed:9003024, PubMed:11677594). 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:10482243, PubMed:9003024). 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 (By similarity). 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). 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: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 (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 (By similarity). 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 (By similarity).By similarity2 Publications4 Publications

GO - Molecular functioni

  • cytokine activity Source: RGD
  • hormone activity Source: RGD
  • peptide hormone receptor binding Source: RGD
  • receptor binding Source: RGD

GO - Biological processi

  • activation of protein kinase C activity Source: UniProtKB
  • adipose tissue development Source: Ensembl
  • adult feeding behavior Source: HGNC
  • bile acid metabolic process Source: Ensembl
  • bone growth Source: UniProtKB
  • bone mineralization involved in bone maturation Source: RGD
  • cAMP-mediated signaling Source: RGD
  • cardiac muscle hypertrophy Source: RGD
  • cellular response to L-ascorbic acid Source: RGD
  • cellular response to retinoic acid Source: RGD
  • central nervous system neuron development Source: Ensembl
  • cholesterol metabolic process Source: Ensembl
  • circadian rhythm Source: RGD
  • eating behavior Source: Ensembl
  • energy reserve metabolic process Source: RGD
  • fatty acid beta-oxidation Source: Ensembl
  • fatty acid catabolic process Source: RGD
  • female pregnancy Source: RGD
  • glucose homeostasis Source: Ensembl
  • glucose metabolic process Source: Ensembl
  • glycerol biosynthetic process Source: RGD
  • hormone metabolic process Source: Ensembl
  • insulin secretion Source: Ensembl
  • interleukin-12 production Source: UniProtKB
  • interleukin-6 production Source: UniProtKB
  • interleukin-6 secretion Source: UniProtKB
  • interleukin-8 secretion Source: UniProtKB
  • intestinal absorption Source: UniProtKB
  • intracellular signal transduction Source: RGD
  • JAK-STAT cascade Source: RGD
  • leptin-mediated signaling pathway Source: UniProtKB
  • leukocyte tethering or rolling Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • 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: RGD
  • negative regulation of glucagon secretion Source: Ensembl
  • negative regulation of glucose import Source: UniProtKB
  • negative regulation of glutamine transport Source: RGD
  • negative regulation of lipid storage Source: RGD
  • negative regulation of metabolic process Source: RGD
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • negative regulation of vasoconstriction Source: RGD
  • ovulation from ovarian follicle Source: RGD
  • phagocytosis Source: UniProtKB
  • placenta development Source: Ensembl
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of cytokine production Source: RGD
  • positive regulation of developmental growth Source: Ensembl
  • positive regulation of fat cell apoptotic process Source: RGD
  • positive regulation of follicle-stimulating hormone secretion Source: RGD
  • positive regulation of hepatic stellate cell activation Source: RGD
  • positive regulation of insulin receptor signaling pathway Source: RGD
  • positive regulation of ion transport Source: RGD
  • positive regulation of JAK-STAT cascade Source: UniProtKB
  • positive regulation of luteinizing hormone secretion Source: RGD
  • positive regulation of MAPK cascade Source: RGD
  • positive regulation of myeloid cell differentiation Source: Ensembl
  • positive regulation of p38MAPK cascade Source: UniProtKB
  • positive regulation of peroxisome proliferator activated receptor signaling pathway Source: RGD
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: RGD
  • positive regulation of STAT protein import into nucleus Source: Ensembl
  • positive regulation of T cell proliferation Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: RGD
  • prostaglandin secretion Source: UniProtKB
  • regulation of angiogenesis Source: UniProtKB
  • regulation of blood pressure Source: RGD
  • 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 gluconeogenesis Source: Ensembl
  • regulation of insulin secretion Source: Ensembl
  • regulation of intestinal cholesterol absorption Source: Ensembl
  • regulation of lipoprotein lipid oxidation Source: RGD
  • 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 steroid biosynthetic process Source: Ensembl
  • response to activity Source: RGD
  • response to dietary excess Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to hypoxia Source: RGD
  • response to insulin Source: Ensembl
  • response to nutrient Source: RGD
  • response to nutrient levels Source: RGD
  • response to vitamin E Source: RGD
  • T cell differentiation Source: UniProtKB
  • tyrosine phosphorylation of STAT protein Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-2586552. Signaling by Leptin.
R-RNO-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi3000. Lep.

Subcellular locationi

  • Secreted 1 Publication

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • extracellular space Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 167146LeptinPRO_0000017690Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi117 ↔ 167By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP50596.

Expressioni

Gene expression databases

GenevisibleiP50596. RN.

Interactioni

GO - Molecular functioni

  • cytokine activity Source: RGD
  • hormone activity Source: RGD
  • peptide hormone receptor binding Source: RGD
  • receptor binding Source: RGD

Protein-protein interaction databases

BioGridi247637. 5 interactions.
STRINGi10116.ENSRNOP00000066184.

Structurei

3D structure databases

ProteinModelPortaliP50596.
SMRiP50596. Positions 24-167.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
GeneTreeiENSGT00390000011772.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiP50596.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG77Q4Z3.
PhylomeDBiP50596.
TreeFamiTF105086.

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.

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

P50596-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCWRPLCRFL WLWSYLSYVQ AVPIHKVQDD TKTLIKTIVT RINDISHTQS
60 70 80 90 100
VSARQRVTGL DFIPGLHPIL SLSKMDQTLA VYQQILTSLP SQNVLQIAHD
110 120 130 140 150
LENLRDLLHL LAFSKSCSLP QTRGLQKPES LDGVLEASLY STEVVALSRL
160
QGSLQDILQQ LDLSPEC
Length:167
Mass (Da):18,866
Last modified:October 1, 1996 - v1
Checksum:i3B5B563DA42EC84E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti32 – 321K → T (PubMed:7794258).Curated
Sequence conflicti163 – 1631L → V in AAC52514 (Ref. 4) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D45862 mRNA. Translation: BAA08296.1.
S78586 mRNA. Translation: AAB34657.2.
D49653 mRNA. Translation: BAA08529.1.
U48849 mRNA. Translation: AAC52514.1.
PIRiPC4034. LTRT.
RefSeqiNP_037208.1. NM_013076.3.
XP_008760984.1. XM_008762762.1.
UniGeneiRn.44444.

Genome annotation databases

EnsembliENSRNOT00000071926; ENSRNOP00000066184; ENSRNOG00000045797.
GeneIDi25608.
KEGGirno:25608.
UCSCiRGD:3000. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D45862 mRNA. Translation: BAA08296.1.
S78586 mRNA. Translation: AAB34657.2.
D49653 mRNA. Translation: BAA08529.1.
U48849 mRNA. Translation: AAC52514.1.
PIRiPC4034. LTRT.
RefSeqiNP_037208.1. NM_013076.3.
XP_008760984.1. XM_008762762.1.
UniGeneiRn.44444.

3D structure databases

ProteinModelPortaliP50596.
SMRiP50596. Positions 24-167.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247637. 5 interactions.
STRINGi10116.ENSRNOP00000066184.

Proteomic databases

PaxDbiP50596.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000071926; ENSRNOP00000066184; ENSRNOG00000045797.
GeneIDi25608.
KEGGirno:25608.
UCSCiRGD:3000. rat.

Organism-specific databases

CTDi3952.
RGDi3000. Lep.

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
GeneTreeiENSGT00390000011772.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiP50596.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG77Q4Z3.
PhylomeDBiP50596.
TreeFamiTF105086.

Enzyme and pathway databases

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

Miscellaneous databases

NextBioi607339.
PROiP50596.

Gene expression databases

GenevisibleiP50596. RN.

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...

Publicationsi

  1. "Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats."
    Ogawa Y., Masuzaki H., Isse N., Okazaki T., Mori K., Shigemoto M., Satoh N., Tamura N., Hosoda K., Yoshimasa Y., Jingami H., Kawada T., Nakao K.
    J. Clin. Invest. 96:1647-1652(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  2. "Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats."
    Funahashi T., Shimomura I., Hiraoka H., Arai T., Takahashi M., Nakamura T., Nozaki S., Yamashita S., Takemura K., Tokunaga K.
    Biochem. Biophys. Res. Commun. 211:469-475(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Adipose tissue.
  3. "Cloning of rat obese cDNA and its expression in obese rats."
    Murakami T., Shima K.
    Biochem. Biophys. Res. Commun. 209:944-952(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: OLETF and Zucker.
    Tissue: Adipose tissue.
  4. Donohoue P.A., Sivitz W.I., Bailey H.L.
    Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-167.
    Strain: Sprague-Dawley.
    Tissue: Adipose tissue.
  5. "Leptin activates neurons in ventrobasal hypothalamus and brainstem."
    Elmquist J.K., Ahima R.S., Maratos-Flier E., Flier J.S., Saper C.B.
    Endocrinology 138:839-842(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area."
    Elias C.F., Aschkenasi C., Lee C., Kelly J., Ahima R.S., Bjorbaek C., Flier J.S., Saper C.B., Elmquist J.K.
    Neuron 23:775-786(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro."
    Park H.Y., Kwon H.M., Lim H.J., Hong B.K., Lee J.Y., Park B.E., Jang Y., Cho S.Y., Kim H.S.
    Exp. Mol. Med. 33:95-102(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Intracellular signaling. Key enzyme in leptin-induced anorexia."
    Niswender K.D., Morton G.J., Stearns W.H., Rhodes C.J., Myers M.G. Jr., Schwartz M.W.
    Nature 413:794-795(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. Cited for: REVIEW OF FUNCTION IN IMMUNITY.
  10. "20 years of leptin: connecting leptin signaling to biological function."
    Allison M.B., Myers M.G. Jr.
    J. Endocrinol. 223:T25-T35(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW OF FUNCTION.

Entry informationi

Entry nameiLEP_RAT
AccessioniPrimary (citable) accession number: P50596
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 11, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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.