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Leptin (Obesity factor)

 G8BLB4_BOVIN            Unreviewed;       167 AA.
G8BLB4;
25-JAN-2012, integrated into UniProtKB/TrEMBL.
25-JAN-2012, sequence version 1.
30-AUG-2017, entry version 53.
RecName: Full=Leptin {ECO:0000256|PIRNR:PIRNR001837};
AltName: Full=Obesity factor {ECO:0000256|PIRNR:PIRNR001837};
Name=ob {ECO:0000313|EMBL:CCE35542.1};
Synonyms=LEP {ECO:0000313|Ensembl:ENSBTAP00000019853};
Bos taurus (Bovine).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
Pecora; Bovidae; Bovinae; Bos.
NCBI_TaxID=9913;
[1] {ECO:0000313|Ensembl:ENSBTAP00000019853, ECO:0000313|Proteomes:UP000009136}
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000019853,
ECO:0000313|Proteomes:UP000009136};
PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C.,
Puiu D., Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S.,
Marcais G., Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
"A whole-genome assembly of the domestic cow, Bos taurus.";
Genome Biol. 10:R42.01-R42.10(2009).
[2] {ECO:0000313|EMBL:CCE35542.1}
NUCLEOTIDE SEQUENCE.
Di Gregorio P., Rando A., Laviano L.;
"sequence of the bovine ob gene.";
Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases.
[3] {ECO:0000313|EMBL:CCE35542.1}
NUCLEOTIDE SEQUENCE.
DI Gregorio P.P.;
Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases.
[4] {ECO:0000313|EMBL:AFN44373.1}
NUCLEOTIDE SEQUENCE.
Martinez R., Abuabara Y., Gallego F., Polanco N., Pedraza A.;
"New Variation in Genes Related to Growth in Colombian Creole
Cattle.";
Submitted (FEB-2012) to the EMBL/GenBank/DDBJ databases.
[5] {ECO:0000313|Ensembl:ENSBTAP00000019853}
IDENTIFICATION.
STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000019853};
Ensembl;
Submitted (MAR-2016) to UniProtKB.
-!- 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. 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.
{ECO:0000256|PIRNR:PIRNR001837}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000256|PIRNR:PIRNR001837}.
-!- SIMILARITY: Belongs to the leptin family.
{ECO:0000256|PIRNR:PIRNR001837}.
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EMBL; DAAA02011496; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; JQ711179; AFN44373.1; -; Genomic_DNA.
EMBL; HE605298; CCE35542.1; -; Genomic_DNA.
RefSeq; NP_776353.2; NM_173928.2.
UniGene; Bt.1939; -.
Ensembl; ENSBTAT00000019853; ENSBTAP00000019853; ENSBTAG00000014911.
GeneID; 280836; -.
KEGG; bta:280836; -.
CTD; 3952; -.
eggNOG; ENOG410IVT0; Eukaryota.
eggNOG; ENOG410Y7NT; LUCA.
GeneTree; ENSGT00390000011772; -.
KO; K05424; -.
OMA; QISNDLE; -.
OrthoDB; EOG091G0Y82; -.
TreeFam; TF105086; -.
Reactome; R-BTA-2586552; Signaling by Leptin.
Reactome; R-BTA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
Reactome; R-BTA-422085; Synthesis, secretion, and deacylation of Ghrelin.
Proteomes; UP000009136; Chromosome 4.
Bgee; ENSBTAG00000014911; -.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0005615; C:extracellular space; IDA:AgBase.
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; IBA:GO_Central.
GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
GO; GO:0008343; P:adult feeding behavior; IEA:Ensembl.
GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
GO; GO:0008206; P:bile acid metabolic process; IEA:Ensembl.
GO; GO:0098868; P:bone growth; IEA:Ensembl.
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; IEA:Ensembl.
GO; GO:0072604; P:interleukin-6 secretion; IEA:Ensembl.
GO; GO:0072606; P:interleukin-8 secretion; IEA:Ensembl.
GO; GO:0050892; P:intestinal absorption; IEA:Ensembl.
GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; IBA:GO_Central.
GO; GO:0010507; P:negative regulation of autophagy; IEA:Ensembl.
GO; GO:0070093; P:negative regulation of glucagon secretion; IEA:Ensembl.
GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
GO; GO:0001890; P:placenta development; IEA:Ensembl.
GO; GO:0048639; P:positive regulation of developmental growth; IEA:Ensembl.
GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IDA:AgBase.
GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IEA:Ensembl.
GO; GO:1900745; P:positive regulation of p38MAPK cascade; IBA:GO_Central.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
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; IEA:Ensembl.
GO; GO:0032008; P:positive regulation of TOR signaling; IBA:GO_Central.
GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
GO; GO:0032310; P:prostaglandin secretion; IEA:Ensembl.
GO; GO:0045765; P:regulation of angiogenesis; IEA:Ensembl.
GO; GO:0046850; P:regulation of bone remodeling; IEA:Ensembl.
GO; GO:0090335; P:regulation of brown fat cell differentiation; IEA:Ensembl.
GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IEA:Ensembl.
GO; GO:0001936; P:regulation of endothelial cell proliferation; IEA:Ensembl.
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:0042269; P:regulation of natural killer cell mediated cytotoxicity; IEA:Ensembl.
GO; GO:0032817; P:regulation of natural killer cell proliferation; IEA:Ensembl.
GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IEA:Ensembl.
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; IDA:AgBase.
GO; GO:0019953; P:sexual reproduction; IEA:Ensembl.
GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
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.
3: Inferred from homology;
Complete proteome {ECO:0000313|Proteomes:UP000009136};
Disulfide bond {ECO:0000256|PIRSR:PIRSR001837-1};
Reference proteome {ECO:0000313|Proteomes:UP000009136};
Secreted {ECO:0000256|PIRNR:PIRNR001837};
Signal {ECO:0000256|SAM:SignalP}.
SIGNAL 1 21 {ECO:0000256|SAM:SignalP}.
CHAIN 22 167 Leptin. {ECO:0000256|SAM:SignalP}.
/FTId=PRO_5010674523.
DISULFID 117 167 {ECO:0000256|PIRSR:PIRSR001837-1}.
SEQUENCE 167 AA; 18663 MW; C9AA16B31AF229CE CRC64;
MRCGPLYRFL WLWPYLSYVE AVPICKVQDD TKTLIKTIVT RINDISHTQS VSSKQRVTGL
DFIPGLHPLL SLSKMDQTLA IYQQILTSLP SRNVVQISND LENLRDLLHL LAASKSCPLP
QVRALESLES LGVVLEASLY STEVVALSRL QGSLQDMLRQ LDLSPGC


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