LEP_HUMAN
ID LEP_HUMAN Reviewed; 167 AA.
AC P41159; O15158; Q56A88;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Leptin {ECO:0000312|HGNC:HGNC:6553};
DE AltName: Full=Obese protein;
DE AltName: Full=Obesity factor;
DE Flags: Precursor;
GN Name=LEP {ECO:0000312|HGNC:HGNC:6553};
GN Synonyms=OB {ECO:0000312|HGNC:HGNC:6553}, OBS {ECO:0000312|HGNC:HGNC:6553};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7789654; DOI=10.2337/diab.44.7.855;
RA Masuzaki H., Ogawa Y., Isse N., Satoh N., Okazaki T., Shigemoto M.,
RA Mori K., Tamura N., Hosoda K., Yoshimasa Y., Jingami H., Kawada T.,
RA Nakao K.;
RT "Human obese gene expression. Adipocyte-specific expression and regional
RT differences in the adipose tissue.";
RL Diabetes 44:855-858(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8626726; DOI=10.1074/jbc.271.8.3971;
RA Gong D.W., Bi S., Pratley R.E., Weintraub B.D.;
RT "Genomic structure and promoter analysis of the human obese gene.";
RL J. Biol. Chem. 271:3971-3974(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Chehab F.F., Lim M.E.;
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7499240; DOI=10.1074/jbc.270.46.27728;
RA Isse N., Ogawa Y., Tamura N., Masuzaki H., Mori K., Okazaki T., Satoh N.,
RA Shigemoto M., Yoshimasa Y., Nishi S., Hosada K., Inazawa J., Nakao K.;
RT "Structural organization and chromosomal assignment of the human obese
RT gene.";
RL J. Biol. Chem. 270:27728-27733(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8621021; DOI=10.2337/diab.45.5.675;
RA Niki T., Mori H., Tamori Y., Kishimoto-Hashiramoto M., Ueno H., Araki S.,
RA Masugi J., Sawant N., Majithia H.R., Rais N., Hashiramoto M., Taniguchi H.,
RA Kasuga M.;
RT "Human obese gene: molecular screening in Japanese and Asian Indian NIDDM
RT patients associated with obesity.";
RL Diabetes 45:675-678(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lu L., Fu Z., Xu M., Fu Y., Hu Z.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-94.
RG SeattleSNPs variation discovery resource;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION.
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 [12]
RP INTERACTION WITH SIGLEC6.
RX PubMed=10428856; DOI=10.1074/jbc.274.32.22729;
RA Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C.,
RA Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F.,
RA Varki A., Kastelein R.A.;
RT "OB-BP1/Siglec-6. A leptin- and sialic acid-binding protein of the
RT immunoglobulin superfamily.";
RL J. Biol. Chem. 274:22729-22738(1999).
RN [13]
RP ERRATUM OF PUBMED:10428856.
RA Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C.,
RA Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F.,
RA Varki A., Kastelein R.A.;
RL J. Biol. Chem. 274:28058-28058(1999).
RN [14]
RP TISSUE SPECIFICITY, AND INDUCTION BY SECRETIN.
RX PubMed=10896907; DOI=10.1136/gut.47.2.178;
RA Sobhani I., Bado A., Vissuzaine C., Buyse M., Kermorgant S., Laigneau J.P.,
RA Attoub S., Lehy T., Henin D., Mignon M., Lewin M.J.;
RT "Leptin secretion and leptin receptor in the human stomach.";
RL Gut 47:178-183(2000).
RN [15]
RP FUNCTION.
RX PubMed=11460888; DOI=10.1038/emm.2001.17;
RA Park H.Y., Kwon H.M., Lim H.J., Hong B.K., Lee J.Y., Park B.E., Jang Y.,
RA Cho S.Y., Kim H.S.;
RT "Potential role of leptin in angiogenesis: leptin induces endothelial cell
RT proliferation and expression of matrix metalloproteinases in vivo and in
RT vitro.";
RL Exp. Mol. Med. 33:95-102(2001).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=12448771; DOI=10.1046/j.0021-8782.2002.00106.x;
RA De Matteis R., Puxeddu R., Riva A., Cinti S.;
RT "Intralobular ducts of human major salivary glands contain leptin and its
RT receptor.";
RL J. Anat. 201:363-370(2002).
RN [17]
RP FUNCTION.
RX PubMed=12504075; DOI=10.1016/s0006-291x(02)02838-3;
RA Zhao Y., Sun R., You L., Gao C., Tian Z.;
RT "Expression of leptin receptors and response to leptin stimulation of human
RT natural killer cell lines.";
RL Biochem. Biophys. Res. Commun. 300:247-252(2003).
RN [18]
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 [19]
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 [20]
RP TISSUE SPECIFICITY.
RX PubMed=16052473; DOI=10.1002/jcb.20521;
RA Solberg R., Aas V., Thoresen G.H., Kase E.T., Drevon C.A., Rustan A.C.,
RA Reseland J.E.;
RT "Leptin expression in human primary skeletal muscle cells is reduced during
RT differentiation.";
RL J. Cell. Biochem. 96:89-96(2005).
RN [21]
RP FUNCTION.
RX PubMed=17344214; DOI=10.1074/jbc.m609798200;
RA Saxena N.K., Vertino P.M., Anania F.A., Sharma D.;
RT "leptin-induced growth stimulation of breast cancer cells involves
RT recruitment of histone acetyltransferases and mediator complex to CYCLIN D1
RT promoter via activation of Stat3.";
RL J. Biol. Chem. 282:13316-13325(2007).
RN [22]
RP FUNCTION.
RX PubMed=18242580; DOI=10.1016/j.bbrc.2007.04.004;
RA Jiang H., Yu J., Guo H., Song H., Chen S.;
RT "up-regulation of survivin by leptin/STAT3 signaling in MCF-7 cells.";
RL Biochem. Biophys. Res. Commun. 368:1-5(2008).
RN [23]
RP FUNCTION.
RX PubMed=19688109; DOI=10.1155/2009/345838;
RA Vuolteenaho K., Koskinen A., Kukkonen M., Nieminen R., Paeivaerinta U.,
RA Moilanen T., Moilanen E.;
RT "Leptin enhances synthesis of proinflammatory mediators in human
RT osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6,
RT and IL-8 production.";
RL Mediators Inflamm. 2009:345838-345838(2009).
RN [24]
RP FUNCTION.
RX PubMed=24340098; DOI=10.1371/journal.pone.0083360;
RA El-Zein O., Kreydiyyeh S.I.;
RT "Leptin inhibits glucose intestinal absorption via PKC, p38MAPK, PI3K and
RT MEK/ERK.";
RL PLoS ONE 8:E83360-E83360(2013).
RN [25]
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 [26]
RP FUNCTION.
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 [27]
RP STRUCTURE BY NMR.
RX PubMed=9166907; DOI=10.1016/s0014-5793(97)00353-0;
RA Kline A.D., Becker G.W., Churgay L.M., Landen B.E., Martin D.K., Muth W.L.,
RA Rathnachalam R., Richardson J.M., Schoner B., Ulmer M., Hale J.E.;
RT "Leptin is a four-helix bundle: secondary structure by NMR.";
RL FEBS Lett. 407:239-242(1997).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=9144295; DOI=10.1038/387206a0;
RA Zhang F., Basinski M.B., Beals J.M., Briggs S.L., Churgay L.M.,
RA Clawson D.K., Dimarchi R.D., Furman T.C., Hale J.E., Hsiung H.M.,
RA Schoner B.E., Smith D.P., Zhang X.Y., Wery J.P., Schevitz R.W.;
RT "Crystal structure of the obese protein leptin-E100.";
RL Nature 387:206-209(1997).
RN [29]
RP VARIANT MET-94.
RA Bartholomew D.W., McClellan J.M.;
RT "A novel polymorphism in the leptin gene.";
RL Hum. Mutat. 12:220-220(1998).
RN [30]
RP VARIANT LEPD TRP-105.
RX PubMed=9500540; DOI=10.1038/ng0398-213;
RA Strobel A., Issad T., Camoin L., Ozata M., Strosberg A.D.;
RT "A leptin missense mutation associated with hypogonadism and morbid
RT obesity.";
RL Nat. Genet. 18:213-215(1998).
RN [31]
RP VARIANT LEPD TYR-100, AND CHARACTERIZATION OF VARIANT LEPD TYR-100.
RX PubMed=25551525; DOI=10.1056/nejmoa1406653;
RA Wabitsch M., Funcke J.B., Lennerz B., Kuhnle-Krahl U., Lahr G.,
RA Debatin K.M., Vatter P., Gierschik P., Moepps B., Fischer-Posovszky P.;
RT "Biologically inactive leptin and early-onset extreme obesity.";
RL N. Engl. J. Med. 372:48-54(2015).
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:17344214, PubMed:15899045, PubMed:19688109). In the
CC hypothalamus, acts as an appetite-regulating factor that induces a
CC decrease in food intake and an increase in energy consumption by
CC inducing anorexinogenic factors and suppressing orexigenic
CC neuropeptides, also regulates bone mass and secretion of hypothalamo-
CC pituitary-adrenal hormones. In the periphery, increases basal
CC metabolism, influences reproductive function, regulates pancreatic
CC beta-cell function and insulin secretion, is pro-angiogenic for
CC endothelial cell and affects innate and adaptive immunity (By
CC similarity) (PubMed:8589726, PubMed:11460888, PubMed:19688109,
CC PubMed:24340098, PubMed:25060689). In the arcuate nucleus of the
CC hypothalamus, activates by depolarization POMC neurons inducing FOS and
CC SOCS3 expression to release anorexigenic peptides and inhibits by
CC hyperpolarization NPY neurons inducing SOCS3 with a consequent
CC reduction on release of orexigenic peptides (By similarity). In
CC addition to its known satiety inducing effect, has a modulatory role in
CC nutrient absorption. In the intestine, reduces glucose absorption by
CC enterocytes by activating PKC and leading to a sequential activation of
CC p38, PI3K and ERK signaling pathways which exerts an inhibitory effect
CC on glucose absorption (PubMed:24340098). Acts as a growth factor on
CC certain tissues, through the activation of different signaling pathways
CC increases expression of genes involved in cell cycle regulation such as
CC CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1
CC pathways (By similarity) (PubMed:17344214). May also play an apoptotic
CC role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression
CC (PubMed:18242580). Pro-angiogenic, has mitogenic activity on vascular
CC endothelial cells and plays a role in matrix remodeling by regulating
CC the expression of matrix metalloproteinases (MMPs) and tissue
CC inhibitors of metalloproteinases (TIMPs) (PubMed:11460888). In innate
CC immunity, modulates the activity and function of neutrophils by
CC increasing chemotaxis and the secretion of oxygen radicals. Increases
CC phagocytosis by macrophages and enhances secretion of pro-inflammatory
CC mediators. Increases cytotoxic ability of NK cells (PubMed:12504075).
CC Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2
CC wich promotes the production of IL6, IL8 and Prostaglandin E2, through
CC a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and
CC MAPK14/p38 (PubMed:15899045, PubMed:19688109). In adaptive immunity,
CC promotes the switch of memory T-cells towards T helper-1 cell immune
CC responses (By similarity). Increases CD4(+)CD25(-) T-cell proliferation
CC and reduces autophagy during TCR (T-cell receptor) stimulation, through
CC MTOR signaling pathway activation and BCL2 up-regulation
CC (PubMed:25060689). {ECO:0000250|UniProtKB:P41160,
CC ECO:0000250|UniProtKB:P50596, ECO:0000269|PubMed:11460888,
CC ECO:0000269|PubMed:12504075, ECO:0000269|PubMed:15899045,
CC ECO:0000269|PubMed:17344214, ECO:0000269|PubMed:18242580,
CC ECO:0000269|PubMed:19688109, ECO:0000269|PubMed:24340098,
CC ECO:0000269|PubMed:25060689, ECO:0000269|PubMed:8589726,
CC ECO:0000305|PubMed:15122202, ECO:0000305|PubMed:25232147}.
CC -!- SUBUNIT: Interacts with SIGLEC6. {ECO:0000269|PubMed:10428856}.
CC -!- INTERACTION:
CC P41159; O75031: HSF2BP; NbExp=3; IntAct=EBI-12994693, EBI-7116203;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25232147}.
CC -!- TISSUE SPECIFICITY: Adipose tissue is the main source of leptin. It is
CC also produced by other peripheral tissues such as the skeletal muscle
CC (PubMed:7789654, PubMed:16052473, PubMed:12448771). Expressed by
CC intercalated and striated tracts of submandibular and parotid salivary
CC gland intralobular ducts (PubMed:12448771). Detected by fundic
CC epithelium of the gastric mucosa (PubMed:10896907). Secreted into blood
CC and gastric juice (PubMed:10896907). {ECO:0000269|PubMed:10896907,
CC ECO:0000269|PubMed:12448771, ECO:0000269|PubMed:16052473,
CC ECO:0000269|PubMed:7789654}.
CC -!- INDUCTION: Induced by secretin. {ECO:0000269|PubMed:10896907}.
CC -!- DISEASE: Leptin deficiency (LEPD) [MIM:614962]: A rare disease
CC characterized by low levels of serum leptin, severe hyperphagia and
CC intractable obesity from an early age. {ECO:0000269|PubMed:25551525,
CC ECO:0000269|PubMed:9500540}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the leptin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Leptin entry;
CC URL="https://en.wikipedia.org/wiki/Leptin";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/lep/";
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DR EMBL; U18915; AAA60470.1; -; mRNA.
DR EMBL; D49487; BAA08448.1; -; mRNA.
DR EMBL; U43653; AAC50400.1; -; mRNA.
DR EMBL; U43415; AAC31660.1; -; Genomic_DNA.
DR EMBL; D63710; BAA09839.1; -; Genomic_DNA.
DR EMBL; D63519; BAA09787.1; -; Genomic_DNA.
DR EMBL; AF008123; AAB63507.1; -; mRNA.
DR EMBL; AY996373; AAX81413.1; -; Genomic_DNA.
DR EMBL; BC060830; AAH60830.1; -; mRNA.
DR EMBL; BC069452; AAH69452.1; -; mRNA.
DR EMBL; BC069527; AAH69527.1; -; mRNA.
DR CCDS; CCDS5800.1; -.
DR PIR; A38952; LTHU.
DR PIR; I53166; I53166.
DR RefSeq; NP_000221.1; NM_000230.2.
DR RefSeq; XP_005250397.1; XM_005250340.4.
DR PDB; 1AX8; X-ray; 2.40 A; A=22-167.
DR PDBsum; 1AX8; -.
DR AlphaFoldDB; P41159; -.
DR PCDDB; P41159; -.
DR SMR; P41159; -.
DR BioGRID; 110143; 17.
DR DIP; DIP-6116N; -.
DR IntAct; P41159; 5.
DR STRING; 9606.ENSP00000312652; -.
DR iPTMnet; P41159; -.
DR MetOSite; P41159; -.
DR PhosphoSitePlus; P41159; -.
DR BioMuta; LEP; -.
DR MassIVE; P41159; -.
DR PaxDb; P41159; -.
DR PeptideAtlas; P41159; -.
DR PRIDE; P41159; -.
DR ProteomicsDB; 55406; -.
DR Antibodypedia; 3389; 1446 antibodies from 43 providers.
DR DNASU; 3952; -.
DR Ensembl; ENST00000308868.5; ENSP00000312652.4; ENSG00000174697.5.
DR GeneID; 3952; -.
DR KEGG; hsa:3952; -.
DR MANE-Select; ENST00000308868.5; ENSP00000312652.4; NM_000230.3; NP_000221.1.
DR UCSC; uc003vml.3; human.
DR CTD; 3952; -.
DR DisGeNET; 3952; -.
DR GeneCards; LEP; -.
DR HGNC; HGNC:6553; LEP.
DR HPA; ENSG00000174697; Group enriched (adipose tissue, breast).
DR MalaCards; LEP; -.
DR MIM; 164160; gene.
DR MIM; 614962; phenotype.
DR neXtProt; NX_P41159; -.
DR OpenTargets; ENSG00000174697; -.
DR Orphanet; 66628; Obesity due to congenital leptin deficiency.
DR PharmGKB; PA228; -.
DR VEuPathDB; HostDB:ENSG00000174697; -.
DR eggNOG; ENOG502S5K5; Eukaryota.
DR GeneTree; ENSGT00390000011772; -.
DR HOGENOM; CLU_132715_0_0_1; -.
DR InParanoid; P41159; -.
DR OMA; MRCGPLC; -.
DR OrthoDB; 1350528at2759; -.
DR PhylomeDB; P41159; -.
DR TreeFam; TF105086; -.
DR PathwayCommons; P41159; -.
DR Reactome; R-HSA-2586552; Signaling by Leptin.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR SignaLink; P41159; -.
DR SIGNOR; P41159; -.
DR BioGRID-ORCS; 3952; 12 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; P41159; -.
DR GeneWiki; Leptin; -.
DR GenomeRNAi; 3952; -.
DR Pharos; P41159; Tbio.
DR PRO; PR:P41159; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P41159; protein.
DR Bgee; ENSG00000174697; Expressed in skin of hip and 100 other tissues.
DR ExpressionAtlas; P41159; baseline and differential.
DR Genevisible; P41159; HS.
DR GO; GO:0005829; C:cytosol; ISS:ARUK-UCL.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; IBA:GO_Central.
DR GO; GO:1990460; F:leptin receptor binding; IDA:ARUK-UCL.
DR GO; GO:0051428; F:peptide hormone receptor binding; IBA:GO_Central.
DR GO; GO:1990051; P:activation of protein kinase C activity; IDA: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; IDA:UniProtKB.
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:0035630; P:bone mineralization involved in bone maturation; IEA:Ensembl.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071298; P:cellular response to L-ascorbic acid; IEA:Ensembl.
DR GO; GO:0044320; P:cellular response to leptin stimulus; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
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:0007623; P:circadian rhythm; 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:0006112; P:energy reserve metabolic process; IBA:GO_Central.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR GO; GO:0006114; P:glycerol biosynthetic 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; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0061037; P:negative regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0070093; P:negative regulation of glucagon secretion; IEA:Ensembl.
DR GO; GO:0046325; P:negative regulation of glucose import; IDA:UniProtKB.
DR GO; GO:2000486; P:negative regulation of glutamine transport; IEA:Ensembl.
DR GO; GO:0010888; P:negative regulation of lipid storage; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
DR GO; GO:0001890; P:placenta development; IDA:DFLAT.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0048639; P:positive regulation of developmental growth; IDA:DFLAT.
DR GO; GO:1904651; P:positive regulation of fat cell apoptotic process; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:0043270; P:positive regulation of ion transport; IEA:Ensembl.
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:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA: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:0001934; P:positive regulation of protein phosphorylation; IDA:ARUK-UCL.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0032310; P:prostaglandin secretion; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0001936; P:regulation of endothelial cell proliferation; IDA: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:0060587; P:regulation of lipoprotein lipid oxidation; IEA:Ensembl.
DR GO; GO:0032814; P:regulation of natural killer cell activation; IDA:UniProtKB.
DR GO; GO:0042269; P:regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0032817; P:regulation of natural killer cell proliferation; IDA:UniProtKB.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IDA:UniProtKB.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
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; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Diabetes mellitus; Disease variant; 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_0000017685"
FT DISULFID 117..167
FT VARIANT 49
FT /note="Missing"
FT /id="VAR_004196"
FT VARIANT 94
FT /note="V -> M (in dbSNP:rs17151919)"
FT /evidence="ECO:0000269|PubMed:9144295, ECO:0000269|Ref.9"
FT /id="VAR_004197"
FT VARIANT 100
FT /note="D -> Y (in LEPD; no effect on secretion; does not
FT bind or activate LEPR; dbSNP:rs724159998)"
FT /evidence="ECO:0000269|PubMed:25551525"
FT /id="VAR_075144"
FT VARIANT 105
FT /note="R -> W (in LEPD; dbSNP:rs104894023)"
FT /evidence="ECO:0000269|PubMed:9500540"
FT /id="VAR_008094"
FT VARIANT 110
FT /note="V -> M (in dbSNP:rs1800564)"
FT /id="VAR_011955"
FT CONFLICT 96
FT /note="Q -> R (in Ref. 8; AAB63507)"
FT /evidence="ECO:0000305"
FT HELIX 25..44
FT /evidence="ECO:0007829|PDB:1AX8"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:1AX8"
FT HELIX 92..114
FT /evidence="ECO:0007829|PDB:1AX8"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:1AX8"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:1AX8"
FT HELIX 142..160
FT /evidence="ECO:0007829|PDB:1AX8"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:1AX8"
SQ SEQUENCE 167 AA; 18641 MW; C91A121E92D37B69 CRC64;
MHWGTLCGFL WLWPYLFYVQ AVPIQKVQDD TKTLIKTIVT RINDISHTQS VSSKQKVTGL
DFIPGLHPIL TLSKMDQTLA VYQQILTSMP SRNVIQISND LENLRDLLHV LAFSKSCHLP
WASGLETLDS LGGVLEASGY STEVVALSRL QGSLQDMLWQ LDLSPGC
