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Protein

Leptin

Gene

LEP

Organism
Felis catus (Cat) (Felis silvestris catus)
Status
Reviewed-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 (By similarity). 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). 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 (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. 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 (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 similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Leptin
Alternative name(s):
Obesity factor
Gene namesi
Name:LEP
Synonyms:OB
OrganismiFelis catus (Cat) (Felis silvestris catus)
Taxonomic identifieri9685 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraFeliformiaFelidaeFelinaeFelis
Proteomesi
  • UP000011712 Componenti: Chromosome A2

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

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_0000017682Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Disulfide bond

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9685.ENSFCAP00000005951.

Structurei

3D structure databases

ProteinModelPortaliQ9N2C1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
GeneTreeiENSGT00390000011772.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiQ9N2C1.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG77Q4Z3.
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.

Q9N2C1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLCGPLCRFL WLWPYLSYVE AVPIRKVQDD TKTLIKTIVT RINDISHTQS
60 70 80 90 100
VSSKQRVAGL DFIPGLHPVL SLSKMDQTLA IYQQILTGLP SRNVVQISND
110 120 130 140 150
LENLRDLLHL LASSKNCPLP RARGLETLES LGGALEASLY STEVVALSRL
160
QASLQDMLWR LDLSPGC
Length:167
Mass (Da):18,584
Last modified:October 1, 2000 - v1
Checksum:i643720DBB0AB4B95
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB041360 mRNA. Translation: BAA95481.1.
RefSeqiNP_001009850.1. NM_001009850.1.
XP_006929412.1. XM_006929350.2.
XP_006929413.1. XM_006929351.2.
XP_006929414.1. XM_006929352.2.
XP_011278812.1. XM_011280510.1.

Genome annotation databases

EnsembliENSFCAT00000006404; ENSFCAP00000005951; ENSFCAG00000006402.
GeneIDi493838.
KEGGifca:493838.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB041360 mRNA. Translation: BAA95481.1.
RefSeqiNP_001009850.1. NM_001009850.1.
XP_006929412.1. XM_006929350.2.
XP_006929413.1. XM_006929351.2.
XP_006929414.1. XM_006929352.2.
XP_011278812.1. XM_011280510.1.

3D structure databases

ProteinModelPortaliQ9N2C1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9685.ENSFCAP00000005951.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSFCAT00000006404; ENSFCAP00000005951; ENSFCAG00000006402.
GeneIDi493838.
KEGGifca:493838.

Organism-specific databases

CTDi3952.

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
GeneTreeiENSGT00390000011772.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiQ9N2C1.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG77Q4Z3.
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.
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning of feline leptin cDNA."
    Sasaki N., Iwase M., Kimura K., Ohishi I., Saito M.
    Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: White adipose tissue.

Entry informationi

Entry nameiLEP_FELCA
AccessioniPrimary (citable) accession number: Q9N2C1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: June 8, 2016
This is version 90 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.