Lep

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 - Molecular functionⁱ

hormone activity Source: Ensembl
peptide hormone receptor binding Source: Ensembl

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

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

View the complete GO annotation on QuickGO ...

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: LeptinUniRule annotation Alternative name(s): Obesity factorUniRule annotation
Gene namesⁱ	Name:LepImported ORF Names:mCG_9137Imported
Organismⁱ	Mus musculus (Mouse)Imported
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus

Organism-specific databases

MGIⁱ	MGI:104663 Lep

Keywords - Cellular componentⁱ

SecretedUniRule annotation

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 21	Sequence analysisAdd BLAST		21
ChainⁱPRO_5014309631	22 – 167	LeptinSequence analysisAdd BLAST		146

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Disulfide bondⁱ	117 ↔ 167	UniRule annotation

Keywords - PTMⁱ

Disulfide bondUniRule annotation

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSMUSG00000059201 Expressed in 61 organ(s), highest expression level in epididymal fat pad

Bgeeⁱ

ENSMUSG00000059201 Expressed in 61 organ(s), highest expression level in epididymal fat pad

Interactionⁱ

GO - Molecular functionⁱ

hormone activity Source: Ensembl
peptide hormone receptor binding Source: Ensembl

View the complete GO annotation on QuickGO ...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the leptin family.UniRule annotation

Keywords - Domainⁱ

SignalSequence analysis

Phylogenomic databases

eggNOGⁱ	ENOG410IVT0 Eukaryota ENOG410Y7NT LUCA
HOVERGENⁱ	HBG007860
KEGG Orthology (KO) More...KOⁱ	K05424
OMAⁱ	QISNDLE
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0Y82

Family and domain databases

InterProⁱ	View protein in InterPro IPR009079 4_helix_cytokine-like_core IPR000065 Leptin
PANTHERⁱ	PTHR11724 PTHR11724, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02024 Leptin, 1 hit
PIRSFⁱ	PIRSF001837 Leptin, 1 hit
PRINTSⁱ	PR00495 LEPTIN
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD005698 Leptin, 1 hit
SUPFAMⁱ	SSF47266 SSF47266, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q544U0-1 [UniParc]FASTA Add 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
NCBI Reference Sequences More...RefSeqⁱ	NP_032519.1, NM_008493.3
UniGeneⁱ	Mm.277072

Genome annotation databases

GeneIDⁱ	16846
KEGGⁱ	mmu:16846

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q544U0	Leptin		MOUSE		167	UniRef100_P41160
Obese protein (Fragment)		CTEID		146
Leptin (Fragment)		MOUSE		98

Protein	Similar proteins		Species	Score	Length	Source
Q544U0	Leptin		MOUSE		167	UniRef90_P41160
Leptin		RAT		167
Leptin		CHICK		163
Obese protein (Fragment)		CTEID		146
Uncharacterized protein		NEOLE		192
+18

Protein	Similar proteins		Species	Score	Length	Source
Q544U0	Leptin		MOUSE		167	UniRef50_P41160
Leptin		RAT		167
Leptin		CHICK		163
Leptin		PIG		167
Leptin		FELCA		167
+210

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
RefSeqⁱ	NP_032519.1, NM_008493.3
UniGeneⁱ	Mm.277072

3D structure databases

ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

GeneIDⁱ	16846
KEGGⁱ	mmu:16846

Organism-specific databases

CTDⁱ	3952
MGIⁱ	MGI:104663 Lep

Phylogenomic databases

eggNOGⁱ	ENOG410IVT0 Eukaryota ENOG410Y7NT LUCA
HOVERGENⁱ	HBG007860
KOⁱ	K05424
OMAⁱ	QISNDLE
OrthoDBⁱ	EOG091G0Y82

Miscellaneous databases

SOURCEⁱ	Search...

SOURCEⁱ

Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000059201 Expressed in 61 organ(s), highest expression level in epididymal fat pad

Bgeeⁱ

ENSMUSG00000059201 Expressed in 61 organ(s), highest expression level in epididymal fat pad

Family and domain databases

InterProⁱ	View protein in InterPro IPR009079 4_helix_cytokine-like_core IPR000065 Leptin
PANTHERⁱ	PTHR11724 PTHR11724, 1 hit
Pfamⁱ	View protein in Pfam PF02024 Leptin, 1 hit
PIRSFⁱ	PIRSF001837 Leptin, 1 hit
PRINTSⁱ	PR00495 LEPTIN
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD005698 Leptin, 1 hit
SUPFAMⁱ	SSF47266 SSF47266, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	Q544U0_MOUSE
Accessionⁱ	Q544U0Primary (citable) accession number: Q544U0
Entry historyⁱ	Integrated into UniProtKB/TrEMBL:	May 24, 2005
	Last sequence update:	May 24, 2005
	Last modified:	October 10, 2018
	This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Unreviewed (UniProtKB/TrEMBL)

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UniProtKB - Q544U0 (Q544U0_MOUSE)

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Leptin

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted

Extracellular region or secreted

Other locations

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ