ID   LEP_MACMU               Reviewed;         167 AA.
AC   Q28504;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=Leptin;
DE   AltName: Full=Obesity factor;
DE   Flags: Precursor;
GN   Name=LEP; Synonyms=OB;
OS   Macaca mulatta (Rhesus macaque).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9544;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Adipose tissue;
RX   PubMed=8810296; DOI=10.1074/jbc.271.41.25327;
RA   Hotta K., Gustafson T.A., Ortmeyer H.K., Bodkin N.L., Nicolson M.A.,
RA   Hansen B.C.;
RT   "Regulation of obese (ob) mRNA and plasma leptin levels in rhesus monkeys.
RT   Effects of insulin, body weight, and non-insulin-dependent diabetes
RT   mellitus.";
RL   J. Biol. Chem. 271:25327-25331(1996).
CC   -!- FUNCTION: Key player in the regulation of energy balance and body
CC       weight control. Once released into the circulation, has central and
CC       peripheral effects by binding LEPR, found in many tissues, which
CC       results in the activation of several major signaling pathways (By
CC       similarity). In the hypothalamus, acts as an appetite-regulating factor
CC       that induces a decrease in food intake and an increase in energy
CC       consumption by inducing anorexinogenic factors and suppressing
CC       orexigenic neuropeptides, also regulates bone mass and secretion of
CC       hypothalamo-pituitary-adrenal hormones. In the periphery, increases
CC       basal metabolism, influences reproductive function, regulates
CC       pancreatic beta-cell function and insulin secretion, is pro-angiogenic
CC       for endothelial cell and affects innate and adaptive immunity (By
CC       similarity). In the arcuate nucleus of the hypothalamus, activates by
CC       depolarization POMC neurons inducing FOS and SOCS3 expression to
CC       release anorexigenic peptides and inhibits by hyperpolarization NPY
CC       neurons inducing SOCS3 with a consequent reduction on release of
CC       orexigenic peptides (By similarity). In addition to its known satiety
CC       inducing effect, has a modulatory role in nutrient absorption. In the
CC       intestine, reduces glucose absorption by enterocytes by activating PKC
CC       and leading to a sequential activation of p38, PI3K and ERK signaling
CC       pathways which exerts an inhibitory effect on glucose absorption (By
CC       similarity). Acts as a growth factor on certain tissues, through the
CC       activation of different signaling pathways increases expression of
CC       genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3
CC       pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways (By similarity).
CC       May also play an apoptotic role via JAK2-STAT3 pathway and up-
CC       regulation of BIRC5 expression. Pro-angiogenic, has mitogenic activity
CC       on vascular endothelial cells and plays a role in matrix remodeling by
CC       regulating the expression of matrix metalloproteinases (MMPs) and
CC       tissue inhibitors of metalloproteinases (TIMPs). In innate immunity,
CC       modulates the activity and function of neutrophils by increasing
CC       chemotaxis and the secretion of oxygen radicals. Increases phagocytosis
CC       by macrophages and enhances secretion of pro-inflammatory mediators.
CC       Increases cytotoxic ability of NK cells. Plays a pro-inflammatory role,
CC       in synergy with IL1B, by inducing NOS2 wich promotes the production of
CC       IL6, IL8 and Prostaglandin E2, through a signaling pathway that
CC       involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38 (By similarity). In
CC       adaptive immunity, promotes the switch of memory T-cells towards T
CC       helper-1 cell immune responses (By similarity). Increases CD4(+)CD25(-)
CC       T-cell proliferation and reduces autophagy during TCR (T-cell receptor)
CC       stimulation, through MTOR signaling pathway activation and BCL2 up-
CC       regulation (By similarity). {ECO:0000250|UniProtKB:P41159,
CC       ECO:0000250|UniProtKB:P41160, ECO:0000250|UniProtKB:P50596}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P41159}.
CC   -!- SIMILARITY: Belongs to the leptin family. {ECO:0000305}.
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DR   EMBL; U58492; AAC50730.1; -; mRNA.
DR   RefSeq; NP_001036220.1; NM_001042755.1.
DR   AlphaFoldDB; Q28504; -.
DR   SMR; Q28504; -.
DR   STRING; 9544.ENSMMUP00000007035; -.
DR   Ensembl; ENSMMUT00000007488; ENSMMUP00000007035; ENSMMUG00000005322.
DR   GeneID; 698728; -.
DR   KEGG; mcc:698728; -.
DR   CTD; 3952; -.
DR   VEuPathDB; HostDB:ENSMMUG00000005322; -.
DR   VGNC; VGNC:81631; LEP.
DR   eggNOG; ENOG502S5K5; Eukaryota.
DR   GeneTree; ENSGT00390000011772; -.
DR   InParanoid; Q28504; -.
DR   OrthoDB; 1350528at2759; -.
DR   Proteomes; UP000006718; Chromosome 3.
DR   Bgee; ENSMMUG00000005322; Expressed in adipose tissue and 5 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; ISS:HGNC-UCL.
DR   GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR   GO; GO:0005179; F:hormone activity; IEA:InterPro.
DR   GO; GO:1990460; F:leptin receptor binding; IEA:Ensembl.
DR   GO; GO:1990051; P:activation of protein kinase C activity; ISS:UniProtKB.
DR   GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
DR   GO; GO:0008343; P:adult feeding behavior; ISS:HGNC-UCL.
DR   GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR   GO; GO:0035904; P:aorta development; IEA:Ensembl.
DR   GO; GO:0008206; P:bile acid metabolic process; IEA:Ensembl.
DR   GO; GO:0098868; P:bone growth; ISS:UniProtKB.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR   GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB.
DR   GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR   GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR   GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR   GO; GO:0051541; P:elastin metabolic process; IEA:Ensembl.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IEA:Ensembl.
DR   GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR   GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR   GO; GO:0042445; P:hormone metabolic process; IEA:Ensembl.
DR   GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR   GO; GO:0050892; P:intestinal absorption; ISS:UniProtKB.
DR   GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0032099; P:negative regulation of appetite; ISS:HGNC-UCL.
DR   GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR   GO; GO:0070093; P:negative regulation of glucagon secretion; IEA:Ensembl.
DR   GO; GO:0046325; P:negative regulation of glucose import; ISS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0006909; P:phagocytosis; ISS:UniProtKB.
DR   GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR   GO; GO:0048639; P:positive regulation of developmental growth; IEA:Ensembl.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:UniProtKB.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR   GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR   GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR   GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
DR   GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR   GO; GO:0032310; P:prostaglandin secretion; ISS:UniProtKB.
DR   GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR   GO; GO:0046850; P:regulation of bone remodeling; ISS:UniProtKB.
DR   GO; GO:0090335; P:regulation of brown fat cell differentiation; ISS:UniProtKB.
DR   GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR   GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR   GO; GO:0001936; P:regulation of endothelial cell proliferation; ISS:UniProtKB.
DR   GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl.
DR   GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
DR   GO; GO:0030300; P:regulation of intestinal cholesterol absorption; IEA:Ensembl.
DR   GO; GO:0032814; P:regulation of natural killer cell activation; ISS:UniProtKB.
DR   GO; GO:0042269; P:regulation of natural killer cell mediated cytotoxicity; ISS:UniProtKB.
DR   GO; GO:0032817; P:regulation of natural killer cell proliferation; ISS:UniProtKB.
DR   GO; GO:0050999; P:regulation of nitric-oxide synthase activity; ISS:UniProtKB.
DR   GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
DR   GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR   GO; GO:0019953; P:sexual reproduction; ISS:UniProtKB.
DR   GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR   GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR000065; Leptin.
DR   PANTHER; PTHR11724; PTHR11724; 1.
DR   Pfam; PF02024; Leptin; 1.
DR   PIRSF; PIRSF001837; Leptin; 1.
DR   PRINTS; PR00495; LEPTIN.
DR   SUPFAM; SSF47266; SSF47266; 1.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Obesity; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..167
FT                   /note="Leptin"
FT                   /id="PRO_0000017686"
FT   DISULFID        117..167
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   167 AA;  18953 MW;  E7D9F30628A5BBE9 CRC64;
     MYWRTLWGFL WLWPYLFYIQ AVPIQKVQSD TKTLIKTIVT RINDISHTQS VSSKQRVTGL
     DFIPGLHPVL TLSQMDQTLA IYQQILINLP SRNVIQISND LENLRDLLHL LAFSKSCHLP
     LASGLETLES LGDVLEASLY STEVVALSRL QGSLQDMLWQ LDLSPGC