ID   LEP_MOUSE               Reviewed;         167 AA.
AC   P41160;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   24-JAN-2024, entry version 189.
DE   RecName: Full=Leptin;
DE   AltName: Full=Obesity factor;
DE   Flags: Precursor;
GN   Name=Lep; Synonyms=Ob;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7984236; DOI=10.1038/372425a0;
RA   Zhang Y., Proenca P., Maffei M., Barone M., Leopold L., Friedman J.M.;
RT   "Positional cloning of the mouse obese gene and its human homologue.";
RL   Nature 372:425-432(1994).
RN   [2]
RP   ERRATUM OF PUBMED:7984236.
RA   Zhang Y., Proenca P., Maffei M., Barone M., Leopold L., Friedman J.M.;
RL   Nature 374:479-479(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RA   Chehab F.F., Lim M.E.;
RL   Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=8589726; DOI=10.1038/ng0396-318;
RA   Chehab F.F., Lim M.E., Lu R.;
RT   "Correction of the sterility defect in homozygous obese female mice by
RT   treatment with the human recombinant leptin.";
RL   Nat. Genet. 12:318-320(1996).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=9732873; DOI=10.1038/29795;
RA   Lord G.M., Matarese G., Howard J.K., Baker R.J., Bloom S.R., Lechler R.I.;
RT   "Leptin modulates the T-cell immune response and reverses starvation-
RT   induced immunosuppression.";
RL   Nature 394:897-901(1998).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=10660043; DOI=10.1016/s0092-8674(00)81558-5;
RA   Ducy P., Amling M., Takeda S., Priemel M., Schilling A.F., Beil F.T.,
RA   Shen J., Vinson C., Rueger J.M., Karsenty G.;
RT   "Leptin inhibits bone formation through a hypothalamic relay: a central
RT   control of bone mass.";
RL   Cell 100:197-207(2000).
RN   [7]
RP   FUNCTION.
RX   PubMed=11373681; DOI=10.1038/35078085;
RA   Cowley M.A., Smart J.L., Rubinstein M., Cerdan M.G., Diano S.,
RA   Horvath T.L., Cone R.D., Low M.J.;
RT   "Leptin activates anorexigenic POMC neurons through a neural network in the
RT   arcuate nucleus.";
RL   Nature 411:480-484(2001).
RN   [8]
RP   FUNCTION.
RX   PubMed=12594516; DOI=10.1038/nature01388;
RA   Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y.,
RA   Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G.,
RA   Schwartz M.W., Myers M.G. Jr.;
RT   "STAT3 signalling is required for leptin regulation of energy balance but
RT   not reproduction.";
RL   Nature 421:856-859(2003).
RN   [9]
RP   REVIEW OF FUNCTION IN IMMUNITY.
RX   PubMed=15122202; DOI=10.1038/nri1350;
RA   La Cava A., Matarese G.;
RT   "The weight of leptin in immunity.";
RL   Nat. Rev. Immunol. 4:371-379(2004).
RN   [10]
RP   FUNCTION.
RX   PubMed=15899045; DOI=10.1186/ar1708;
RA   Otero M., Lago R., Lago F., Reino J.J., Gualillo O.;
RT   "signaling pathway involved in nitric oxide synthase type II activation in
RT   chondrocytes: synergistic effect of leptin with interleukin-1.";
RL   Arthritis Res. Ther. 7:R581-R591(2005).
RN   [11]
RP   FUNCTION.
RX   PubMed=16825198; DOI=10.1074/jbc.m601991200;
RA   Gonzalez R.R., Cherfils S., Escobar M., Yoo J.H., Carino C., Styer A.K.,
RA   Sullivan B.T., Sakamoto H., Olawaiye A., Serikawa T., Lynch M.P.,
RA   Rueda B.R.;
RT   "Leptin signaling promotes the growth of mammary tumors and increases the
RT   expression of vascular endothelial growth factor (VEGF) and its receptor
RT   type two (VEGF-R2).";
RL   J. Biol. Chem. 281:26320-26328(2006).
RN   [12]
RP   FUNCTION.
RX   PubMed=20620997; DOI=10.1016/j.cmet.2010.05.010;
RA   Ramadori G., Fujikawa T., Fukuda M., Anderson J., Morgan D.A.,
RA   Mostoslavsky R., Stuart R.C., Perello M., Vianna C.R., Nillni E.A.,
RA   Rahmouni K., Coppari R.;
RT   "SIRT1 deacetylase in POMC neurons is required for homeostatic defenses
RT   against diet-induced obesity.";
RL   Cell Metab. 12:78-87(2010).
RN   [13]
RP   REVIEW OF FUNCTION.
RX   PubMed=25232147; DOI=10.1530/joe-14-0404;
RA   Allison M.B., Myers M.G. Jr.;
RT   "20 years of leptin: connecting leptin signaling to biological function.";
RL   J. Endocrinol. 223:T25-T35(2014).
RN   [14]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=25060689; DOI=10.1016/j.metabol.2014.06.010;
RA   Cassano S., Pucino V., La Rocca C., Procaccini C., De Rosa V., Marone G.,
RA   Matarese G.;
RT   "Leptin modulates autophagy in human CD4+CD25- conventional T cells.";
RL   Metabolism 63:1272-1279(2014).
RN   [15]
RP   FUNCTION.
RX   PubMed=25383904; DOI=10.1038/nn.3861;
RA   Flak J.N., Patterson C.M., Garfield A.S., D'Agostino G., Goforth P.B.,
RA   Sutton A.K., Malec P.A., Wong J.M., Germani M., Jones J.C., Rajala M.,
RA   Satin L., Rhodes C.J., Olson D.P., Kennedy R.T., Heisler L.K.,
RA   Myers M.G. Jr.;
RT   "Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative
RT   energy balance.";
RL   Nat. Neurosci. 17:1744-1750(2014).
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
CC       (PubMed:15899045, PubMed:16825198, PubMed:11373681, PubMed:12594516,
CC       PubMed:20620997). In the hypothalamus, acts as an appetite-regulating
CC       factor 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) (PubMed:8589726, PubMed:10660043, PubMed:25383904,
CC       PubMed:25060689, PubMed:9732873, PubMed:12594516). In the arcuate
CC       nucleus of the hypothalamus, activates by depolarization POMC neurons
CC       inducing FOS and SOCS3 expression to release anorexigenic peptides and
CC       inhibits by hyperpolarization NPY neurons inducing SOCS3 with a
CC       consequent reduction on release of orexigenic peptides (By similarity)
CC       (PubMed:20620997, PubMed:11373681). 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. Acts
CC       as a growth factor on certain tissues, through the activation of
CC       different signaling pathways increases expression of genes involved in
CC       cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA,
CC       via MAPK1/3 and PI3K-AKT1 pathways (By similarity) (PubMed:16825198,
CC       PubMed:20620997). May also play an apoptotic role via JAK2-STAT3
CC       pathway and up-regulation of BIRC5 expression (By similarity). Pro-
CC       angiogenic, has mitogenic activity on vascular endothelial cells and
CC       plays a role in matrix remodeling by regulating the expression of
CC       matrix metalloproteinases (MMPs) and tissue inhibitors of
CC       metalloproteinases (TIMPs) (PubMed:16825198). 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 (Probable). Plays a pro-
CC       inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes
CC       the production of IL6, IL8 and Prostaglandin E2, through a signaling
CC       pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38
CC       (PubMed:15899045). In adaptive immunity, promotes the switch of memory
CC       T-cells towards T helper-1 cell immune responses (By similarity).
CC       Increases CD4(+)CD25(-) T cells proliferation and reduces autophagy
CC       during TCR (T cell receptor) stimulation, through MTOR signaling
CC       pathway activation and BCL2 up-regulation (PubMed:25060689).
CC       {ECO:0000250|UniProtKB:P41159, ECO:0000250|UniProtKB:P50596,
CC       ECO:0000269|PubMed:10660043, ECO:0000269|PubMed:11373681,
CC       ECO:0000269|PubMed:12594516, ECO:0000269|PubMed:15899045,
CC       ECO:0000269|PubMed:16825198, ECO:0000269|PubMed:20620997,
CC       ECO:0000269|PubMed:25060689, ECO:0000269|PubMed:25383904,
CC       ECO:0000269|PubMed:8589726, ECO:0000269|PubMed:9732873,
CC       ECO:0000305|PubMed:15122202, ECO:0000305|PubMed:25232147}.
CC   -!- INTERACTION:
CC       P41160; P48356: Lepr; NbExp=6; IntAct=EBI-16108810, EBI-2257257;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25232147}.
CC   -!- DISEASE: Note=Defects in Lep are the cause of profound obesity and type
CC       II diabetes.
CC   -!- DISRUPTION PHENOTYPE: Mutants are severely obese and sterile
CC       (PubMed:8589726). Animals have an increased bone formation leading to
CC       high bone mass (PubMed:10660043). Have impaired T-cell immunity, Th2
CC       responses are favoured in mutants (PubMed:9732873). CD4(+)CD25(-) T-
CC       cells of mutant mice show high levels of autophagy (PubMed:25060689).
CC       {ECO:0000269|PubMed:10660043, ECO:0000269|PubMed:25060689,
CC       ECO:0000269|PubMed:8589726, ECO:0000269|PubMed:9732873}.
CC   -!- SIMILARITY: Belongs to the leptin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
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DR   EMBL; U18812; AAA64564.1; -; mRNA.
DR   EMBL; U22421; AAA64213.1; -; Genomic_DNA.
DR   CCDS; CCDS19955.1; -.
DR   PIR; S50863; LTMS.
DR   RefSeq; NP_032519.1; NM_008493.3.
DR   PDB; 7Z3P; X-ray; 1.94 A; A=22-167.
DR   PDB; 7Z3R; X-ray; 2.95 A; A=20-167.
DR   PDB; 8AVB; EM; 4.43 A; A=21-167.
DR   PDB; 8AVC; EM; 4.60 A; A/C/E=21-167.
DR   PDB; 8AVD; EM; 4.42 A; A/C/E=21-167.
DR   PDB; 8B7Q; EM; 4.02 A; A=21-167.
DR   PDB; 8DH8; EM; 5.90 A; C=22-162.
DR   PDB; 8DH9; EM; 4.50 A; C/D=1-167.
DR   PDB; 8DHA; EM; 3.80 A; C=22-167.
DR   PDBsum; 7Z3P; -.
DR   PDBsum; 7Z3R; -.
DR   PDBsum; 8AVB; -.
DR   PDBsum; 8AVC; -.
DR   PDBsum; 8AVD; -.
DR   PDBsum; 8B7Q; -.
DR   PDBsum; 8DH8; -.
DR   PDBsum; 8DH9; -.
DR   PDBsum; 8DHA; -.
DR   AlphaFoldDB; P41160; -.
DR   EMDB; EMD-15677; -.
DR   EMDB; EMD-27432; -.
DR   EMDB; EMD-27433; -.
DR   EMDB; EMD-27434; -.
DR   SMR; P41160; -.
DR   BioGRID; 201138; 4.
DR   CORUM; P41160; -.
DR   DIP; DIP-60999N; -.
DR   IntAct; P41160; 1.
DR   STRING; 10090.ENSMUSP00000067046; -.
DR   PhosphoSitePlus; P41160; -.
DR   CPTAC; CPTAC-1473; -.
DR   PaxDb; 10090-ENSMUSP00000067046; -.
DR   ProteomicsDB; 265060; -.
DR   Antibodypedia; 3389; 1530 antibodies from 43 providers.
DR   DNASU; 16846; -.
DR   Ensembl; ENSMUST00000069789.12; ENSMUSP00000067046.6; ENSMUSG00000059201.13.
DR   GeneID; 16846; -.
DR   KEGG; mmu:16846; -.
DR   UCSC; uc009bcv.1; mouse.
DR   AGR; MGI:104663; -.
DR   CTD; 3952; -.
DR   MGI; MGI:104663; Lep.
DR   VEuPathDB; HostDB:ENSMUSG00000059201; -.
DR   eggNOG; ENOG502S5K5; Eukaryota.
DR   GeneTree; ENSGT00390000011772; -.
DR   HOGENOM; CLU_132715_0_0_1; -.
DR   InParanoid; P41160; -.
DR   OMA; MRCGPLC; -.
DR   OrthoDB; 5346301at2759; -.
DR   PhylomeDB; P41160; -.
DR   TreeFam; TF105086; -.
DR   Reactome; R-MMU-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR   Reactome; R-MMU-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR   BioGRID-ORCS; 16846; 0 hits in 79 CRISPR screens.
DR   ChiTaRS; H2-Ob; mouse.
DR   PRO; PR:P41160; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; P41160; Protein.
DR   Bgee; ENSMUSG00000059201; Expressed in thoracic mammary gland and 51 other cell types or tissues.
DR   ExpressionAtlas; P41160; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0005179; F:hormone activity; ISO:MGI.
DR   GO; GO:1990460; F:leptin receptor binding; ISO:MGI.
DR   GO; GO:0051428; F:peptide hormone receptor binding; ISO:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:1990051; P:activation of protein kinase C activity; ISS:UniProtKB.
DR   GO; GO:0060612; P:adipose tissue development; IGI:MGI.
DR   GO; GO:0008343; P:adult feeding behavior; IDA:HGNC-UCL.
DR   GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR   GO; GO:0035904; P:aorta development; IMP:MGI.
DR   GO; GO:0008206; P:bile acid metabolic process; IDA:MGI.
DR   GO; GO:0098868; P:bone growth; IMP:UniProtKB.
DR   GO; GO:0035630; P:bone mineralization involved in bone maturation; ISO:MGI.
DR   GO; GO:0003300; P:cardiac muscle hypertrophy; ISO:MGI.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IDA:MGI.
DR   GO; GO:0071298; P:cellular response to L-ascorbic acid; IEA:Ensembl.
DR   GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB.
DR   GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR   GO; GO:0021954; P:central nervous system neuron development; IMP:MGI.
DR   GO; GO:0008203; P:cholesterol metabolic process; IGI:MGI.
DR   GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR   GO; GO:0008340; P:determination of adult lifespan; IGI:MGI.
DR   GO; GO:0042755; P:eating behavior; IGI:MGI.
DR   GO; GO:0051541; P:elastin metabolic process; IMP:MGI.
DR   GO; GO:0006112; P:energy reserve metabolic process; ISO:MGI.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IGI:MGI.
DR   GO; GO:0009062; P:fatty acid catabolic process; ISO:MGI.
DR   GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR   GO; GO:0042593; P:glucose homeostasis; IGI:MGI.
DR   GO; GO:0006006; P:glucose metabolic process; IMP:MGI.
DR   GO; GO:0006114; P:glycerol biosynthetic process; ISO:MGI.
DR   GO; GO:0042445; P:hormone metabolic process; IMP:MGI.
DR   GO; GO:0030073; P:insulin secretion; IGI:MGI.
DR   GO; GO:0050892; P:intestinal absorption; ISS:UniProtKB.
DR   GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR   GO; GO:0033210; P:leptin-mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0050901; P:leukocyte tethering or rolling; ISO:MGI.
DR   GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0032099; P:negative regulation of appetite; IDA: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; IMP:UniProtKB.
DR   GO; GO:0061037; P:negative regulation of cartilage development; ISO:MGI.
DR   GO; GO:0070093; P:negative regulation of glucagon secretion; IDA:BHF-UCL.
DR   GO; GO:0046325; P:negative regulation of glucose import; ISS:UniProtKB.
DR   GO; GO:2000486; P:negative regulation of glutamine transport; ISO:MGI.
DR   GO; GO:0010888; P:negative regulation of lipid storage; ISO:MGI.
DR   GO; GO:0009892; P:negative regulation of metabolic process; ISO:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0045906; P:negative regulation of vasoconstriction; ISO:MGI.
DR   GO; GO:0001542; P:ovulation from ovarian follicle; ISO:MGI.
DR   GO; GO:0006909; P:phagocytosis; IDA:UniProtKB.
DR   GO; GO:0001890; P:placenta development; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR   GO; GO:0048639; P:positive regulation of developmental growth; ISO:MGI.
DR   GO; GO:1904651; P:positive regulation of fat cell apoptotic process; ISO:MGI.
DR   GO; GO:0046881; P:positive regulation of follicle-stimulating hormone secretion; IEA:Ensembl.
DR   GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; ISO:MGI.
DR   GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:UniProtKB.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR   GO; GO:0033686; P:positive regulation of luteinizing hormone secretion; IEA:Ensembl.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR   GO; GO:0043270; P:positive regulation of monoatomic ion transport; ISO:MGI.
DR   GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR   GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; ISO:MGI.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB.
DR   GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:BHF-UCL.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR   GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR   GO; GO:0032008; P:positive regulation of TOR signaling; ISO:MGI.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR   GO; GO:0032310; P:prostaglandin secretion; ISS:UniProtKB.
DR   GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; ISO:MGI.
DR   GO; GO:0046850; P:regulation of bone remodeling; IMP:UniProtKB.
DR   GO; GO:0090335; P:regulation of brown fat cell differentiation; IDA:UniProtKB.
DR   GO; GO:0051726; P:regulation of cell cycle; IDA: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:0045598; P:regulation of fat cell differentiation; IGI:MGI.
DR   GO; GO:0006111; P:regulation of gluconeogenesis; IMP:MGI.
DR   GO; GO:0050796; P:regulation of insulin secretion; IMP:MGI.
DR   GO; GO:0030300; P:regulation of intestinal cholesterol absorption; IDA:MGI.
DR   GO; GO:0046890; P:regulation of lipid biosynthetic process; IGI:MGI.
DR   GO; GO:0060587; P:regulation of lipoprotein lipid oxidation; ISO:MGI.
DR   GO; GO:0019222; P:regulation of metabolic process; IMP:MGI.
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; IDA:UniProtKB.
DR   GO; GO:1900180; P:regulation of protein localization to nucleus; IMP:MGI.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0050810; P:regulation of steroid biosynthetic process; IMP:MGI.
DR   GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR   GO; GO:0002021; P:response to dietary excess; IMP:MGI.
DR   GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR   GO; GO:0032868; P:response to insulin; IMP:MGI.
DR   GO; GO:0033197; P:response to vitamin E; IEA:Ensembl.
DR   GO; GO:0019953; P:sexual reproduction; IMP:UniProtKB.
DR   GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB.
DR   GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR000065; Leptin.
DR   PANTHER; PTHR11724; LEPTIN; 1.
DR   PANTHER; PTHR11724:SF1; LEPTIN; 1.
DR   Pfam; PF02024; Leptin; 1.
DR   PIRSF; PIRSF001837; Leptin; 1.
DR   PRINTS; PR00495; LEPTIN.
DR   SUPFAM; SSF47266; 4-helical cytokines; 1.
DR   Genevisible; P41160; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Diabetes mellitus; Disulfide bond; Obesity;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..167
FT                   /note="Leptin"
FT                   /id="PRO_0000017687"
FT   DISULFID        117..167
FT                   /evidence="ECO:0000250"
FT   VARIANT         49
FT                   /note="Missing (in 30% the clones)"
FT   HELIX           24..45
FT                   /evidence="ECO:0007829|PDB:7Z3P"
FT   HELIX           46..49
FT                   /evidence="ECO:0007829|PDB:7Z3R"
FT   STRAND          53..55
FT                   /evidence="ECO:0007829|PDB:7Z3R"
FT   HELIX           72..87
FT                   /evidence="ECO:0007829|PDB:7Z3P"
FT   HELIX           92..114
FT                   /evidence="ECO:0007829|PDB:7Z3P"
FT   HELIX           131..137
FT                   /evidence="ECO:0007829|PDB:7Z3R"
FT   HELIX           142..160
FT                   /evidence="ECO:0007829|PDB:7Z3P"
SQ   SEQUENCE   167 AA;  18709 MW;  D6783E6C76FD7116 CRC64;
     MCWRPLCRFL WLWSYLSYVQ AVPIQKVQDD TKTLIKTIVT RINDISHTQS VSAKQRVTGL
     DFIPGLHPIL SLSKMDQTLA VYQQVLTSLP SQNVLQIAND LENLRDLLHL LAFSKSCSLP
     QTSGLQKPES LDGVLEASLY STEVVALSRL QGSLQDILQQ LDVSPEC
//