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Leptin (Obesity factor)

 LEP_FELCA               Reviewed;         167 AA.
Q9N2C1;
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
01-OCT-2000, sequence version 1.
30-AUG-2017, entry version 97.
RecName: Full=Leptin;
AltName: Full=Obesity factor;
Flags: Precursor;
Name=LEP; Synonyms=OB;
Felis catus (Cat) (Felis silvestris catus).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae;
Felinae; Felis.
NCBI_TaxID=9685;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=White adipose tissue;
Sasaki N., Iwase M., Kimura K., Ohishi I., Saito M.;
"Molecular cloning of feline leptin cDNA.";
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: 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).
{ECO:0000250|UniProtKB:P41159, ECO:0000250|UniProtKB:P41160,
ECO:0000250|UniProtKB:P50596}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P41159}.
-!- SIMILARITY: Belongs to the leptin family. {ECO:0000305}.
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EMBL; AB041360; BAA95481.1; -; mRNA.
RefSeq; NP_001009850.1; NM_001009850.1.
RefSeq; XP_006929412.1; XM_006929350.3.
RefSeq; XP_006929413.1; XM_006929351.3.
RefSeq; XP_006929414.1; XM_006929352.3.
RefSeq; XP_011278812.1; XM_011280510.2.
ProteinModelPortal; Q9N2C1; -.
SMR; Q9N2C1; -.
STRING; 9685.ENSFCAP00000005951; -.
Ensembl; ENSFCAT00000006404; ENSFCAP00000005951; ENSFCAG00000006402.
GeneID; 493838; -.
KEGG; fca:493838; -.
CTD; 3952; -.
eggNOG; ENOG410IVT0; Eukaryota.
eggNOG; ENOG410Y7NT; LUCA.
GeneTree; ENSGT00390000011772; -.
HOGENOM; HOG000252923; -.
HOVERGEN; HBG007860; -.
InParanoid; Q9N2C1; -.
KO; K05424; -.
OMA; QISNDLE; -.
OrthoDB; EOG091G0Y82; -.
TreeFam; TF105086; -.
Proteomes; UP000011712; Chromosome A2.
Bgee; ENSFCAG00000006402; -.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0005615; C:extracellular space; ISS:HGNC.
GO; GO:0008083; F:growth factor activity; IEA:Ensembl.
GO; GO:0005179; F:hormone activity; IBA:GO_Central.
GO; GO:0051428; F:peptide hormone receptor binding; IBA:GO_Central.
GO; GO:1990051; P:activation of protein kinase C activity; ISS:UniProtKB.
GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
GO; GO:0008343; P:adult feeding behavior; ISS:HGNC.
GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
GO; GO:0008206; P:bile acid metabolic process; IEA:Ensembl.
GO; GO:0098868; P:bone growth; ISS:UniProtKB.
GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB.
GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl.
GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
GO; GO:0042755; P:eating behavior; IEA:Ensembl.
GO; GO:0006112; P:energy reserve metabolic process; IBA:GO_Central.
GO; GO:0006635; P:fatty acid beta-oxidation; IEA:Ensembl.
GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
GO; GO:0042445; P:hormone metabolic process; IEA:Ensembl.
GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
GO; GO:0032615; P:interleukin-12 production; ISS:UniProtKB.
GO; GO:0032635; P:interleukin-6 production; ISS:UniProtKB.
GO; GO:0072604; P:interleukin-6 secretion; ISS:UniProtKB.
GO; GO:0072606; P:interleukin-8 secretion; ISS:UniProtKB.
GO; GO:0050892; P:intestinal absorption; ISS:UniProtKB.
GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
GO; GO:0032099; P:negative regulation of appetite; ISS:HGNC.
GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
GO; GO:0070093; P:negative regulation of glucagon secretion; IEA:Ensembl.
GO; GO:0046325; P:negative regulation of glucose import; ISS:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0006909; P:phagocytosis; ISS:UniProtKB.
GO; GO:0001890; P:placenta development; IEA:Ensembl.
GO; GO:0048639; P:positive regulation of developmental growth; IEA:Ensembl.
GO; GO:0046427; P:positive regulation of JAK-STAT cascade; ISS:UniProtKB.
GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IEA:Ensembl.
GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
GO; GO:2000366; P:positive regulation of STAT protein import into nucleus; IBA:GO_Central.
GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
GO; GO:0032310; P:prostaglandin secretion; ISS:UniProtKB.
GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
GO; GO:0046850; P:regulation of bone remodeling; ISS:UniProtKB.
GO; GO:0090335; P:regulation of brown fat cell differentiation; ISS:UniProtKB.
GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
GO; GO:0001936; P:regulation of endothelial cell proliferation; ISS:UniProtKB.
GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl.
GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
GO; GO:0030300; P:regulation of intestinal cholesterol absorption; IEA:Ensembl.
GO; GO:0032814; P:regulation of natural killer cell activation; ISS:UniProtKB.
GO; GO:0042269; P:regulation of natural killer cell mediated cytotoxicity; ISS:UniProtKB.
GO; GO:0032817; P:regulation of natural killer cell proliferation; ISS:UniProtKB.
GO; GO:0050999; P:regulation of nitric-oxide synthase activity; ISS:UniProtKB.
GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
GO; GO:0032868; P:response to insulin; ISS:AgBase.
GO; GO:0019953; P:sexual reproduction; ISS:UniProtKB.
GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IBA:GO_Central.
InterPro; IPR009079; 4_helix_cytokine-like_core.
InterPro; IPR000065; Leptin.
PANTHER; PTHR11724; PTHR11724; 1.
Pfam; PF02024; Leptin; 1.
PIRSF; PIRSF001837; Leptin; 1.
PRINTS; PR00495; LEPTIN.
ProDom; PD005698; Leptin; 1.
SUPFAM; SSF47266; SSF47266; 1.
2: Evidence at transcript level;
Complete proteome; Disulfide bond; Obesity; Reference proteome;
Secreted; Signal.
SIGNAL 1 21 {ECO:0000255}.
CHAIN 22 167 Leptin.
/FTId=PRO_0000017682.
DISULFID 117 167 {ECO:0000250}.
SEQUENCE 167 AA; 18584 MW; 643720DBB0AB4B95 CRC64;
MLCGPLCRFL WLWPYLSYVE AVPIRKVQDD TKTLIKTIVT RINDISHTQS VSSKQRVAGL
DFIPGLHPVL SLSKMDQTLA IYQQILTGLP SRNVVQISND LENLRDLLHL LASSKNCPLP
RARGLETLES LGGALEASLY STEVVALSRL QASLQDMLWR LDLSPGC


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