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 11-NOV-2015, entry version 157. DE RecName: Full=Leptin; DE AltName: Full=Obese protein; DE AltName: Full=Obesity factor; DE Flags: Precursor; GN Name=LEP; Synonyms=OB, OBS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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. 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]. 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 RT regional 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., RA Satoh N., Shigemoto M., Yoshimasa Y., Nishi S., Hosada K., Inazawa J., RA 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., RA Araki S., Masugi J., Sawant N., Majithia H.R., Rais N., RA Hashiramoto M., Taniguchi H., Kasuga M.; RT "Human obese gene: molecular screening in Japanese and Asian Indian RT NIDDM 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] 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 [12] RP ERRATUM. 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 [13] 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., RA Muth W.L., Rathnachalam R., Richardson J.M., Schoner B., Ulmer M., RA Hale J.E.; RT "Leptin is a four-helix bundle: secondary structure by NMR."; RL FEBS Lett. 407:239-242(1997). RN [14] 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 [15] 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 [16] 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). CC -!- FUNCTION: May function as part of a signaling pathway that acts to CC regulate the size of the body fat depot. An increase in the level CC of LEP may act directly or indirectly on the CNS to inhibit food CC intake and/or regulate energy expenditure as part of a homeostatic CC mechanism to maintain constancy of the adipose mass. CC -!- SUBUNIT: Interacts with SIGLEC6. {ECO:0000269|PubMed:10428856}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- DISEASE: Leptin deficiency (LEPD) [MIM:614962]: A rare disease CC characterized by low levels of serum leptin, severe hyperphagia CC and intractable obesity from an early age. CC {ECO:0000269|PubMed:9500540}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the leptin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=R&D Systems' cytokine mini-reviews: Leptin; CC URL="http://www.rndsystems.com/molecule_detail.aspx?m=1773"; 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_005250340.3. DR UniGene; Hs.194236; -. DR PDB; 1AX8; X-ray; 2.40 A; A=22-167. DR PDBsum; 1AX8; -. DR ProteinModelPortal; P41159; -. DR BioGrid; 110143; 4. DR DIP; DIP-6116N; -. DR STRING; 9606.ENSP00000312652; -. DR PhosphoSite; P41159; -. DR BioMuta; LEP; -. DR PaxDb; P41159; -. DR PeptideAtlas; P41159; -. DR PRIDE; P41159; -. DR DNASU; 3952; -. DR Ensembl; ENST00000308868; ENSP00000312652; ENSG00000174697. DR GeneID; 3952; -. DR KEGG; hsa:3952; -. DR UCSC; uc003vml.2; human. DR CTD; 3952; -. DR GeneCards; LEP; -. DR HGNC; HGNC:6553; LEP. DR HPA; CAB010490; -. DR HPA; CAB016730; -. DR HPA; HPA030721; -. DR MIM; 164160; gene. DR MIM; 614962; phenotype. DR neXtProt; NX_P41159; -. DR Orphanet; 66628; Obesity due to congenital leptin deficiency. DR PharmGKB; PA228; -. DR eggNOG; ENOG410IVT0; Eukaryota. DR eggNOG; ENOG410Y7NT; LUCA. DR GeneTree; ENSGT00390000011772; -. DR HOGENOM; HOG000252923; -. DR HOVERGEN; HBG007860; -. DR InParanoid; P41159; -. DR KO; K05424; -. DR OMA; INDISHT; -. DR OrthoDB; EOG77Q4Z3; -. DR PhylomeDB; P41159; -. DR TreeFam; TF105086; -. 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 EvolutionaryTrace; P41159; -. DR GeneWiki; Leptin; -. DR GenomeRNAi; 3952; -. DR NextBio; 15501; -. DR PRO; PR:P41159; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; P41159; -. DR CleanEx; HS_LEP; -. DR ExpressionAtlas; P41159; baseline and differential. DR Genevisible; P41159; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:HGNC. DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl. DR GO; GO:0008343; P:adult feeding behavior; ISS:HGNC. DR GO; GO:0008206; P:bile acid metabolic process; IEA:Ensembl. 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:0071298; P:cellular response to L-ascorbic acid; IEA:Ensembl. 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:0042755; P:eating behavior; IEA:Ensembl. DR GO; GO:0006112; P:energy reserve metabolic process; TAS:ProtInc. 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:0033210; P:leptin-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0050901; P:leukocyte tethering or rolling; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0032099; P:negative regulation of appetite; ISS:HGNC. 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:2000486; P:negative regulation of glutamine transport; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; 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:0001890; P:placenta development; IDA:DFLAT. DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl. DR GO; GO:0048639; P:positive regulation of developmental growth; IDA:DFLAT. 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: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; IEA:Ensembl. DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; IEA:Ensembl. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:2000366; P:positive regulation of STAT protein import into nucleus; IEA:Ensembl. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IEA:Ensembl. DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl. DR GO; GO:0045598; P:regulation of fat cell differentiation; IEA:Ensembl. 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:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl. DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl. 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; IPR012351; 4_helix_cytokine_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 ProDom; PD005698; Leptin; 1. DR SUPFAM; SSF47266; SSF47266; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Diabetes mellitus; Disease mutation; KW Disulfide bond; Obesity; Polymorphism; Reference proteome; Secreted; KW Signal. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 167 Leptin. FT /FTId=PRO_0000017685. FT DISULFID 117 167 FT VARIANT 49 49 Missing. FT /FTId=VAR_004196. FT VARIANT 94 94 V -> M (in dbSNP:rs17151919). FT {ECO:0000269|Ref.15, ECO:0000269|Ref.9}. FT /FTId=VAR_004197. FT VARIANT 105 105 R -> W (in LEPD; dbSNP:rs104894023). FT {ECO:0000269|PubMed:9500540}. FT /FTId=VAR_008094. FT VARIANT 110 110 V -> M (in dbSNP:rs1800564). FT /FTId=VAR_011955. FT CONFLICT 96 96 Q -> R (in Ref. 8; AAB63507). FT {ECO:0000305}. FT HELIX 25 44 {ECO:0000244|PDB:1AX8}. FT HELIX 72 87 {ECO:0000244|PDB:1AX8}. FT HELIX 92 114 {ECO:0000244|PDB:1AX8}. FT HELIX 128 131 {ECO:0000244|PDB:1AX8}. FT HELIX 132 135 {ECO:0000244|PDB:1AX8}. FT HELIX 142 160 {ECO:0000244|PDB:1AX8}. FT HELIX 161 163 {ECO:0000244|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 //