LEP_PIG
ID LEP_PIG Reviewed; 167 AA.
AC Q29406; O19095; Q95251;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Leptin;
DE AltName: Full=Obesity factor;
DE Flags: Precursor;
GN Name=LEP; Synonyms=OB, OBS;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adipose tissue;
RA Louis C.F.;
RT "Cloning and tissue distribution of leptin in the pig.";
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Landrace;
RA Robert C., Palin M.-F., Coulombe N., Roberge C., Silversides F.G.,
RA Benkel B.F., McKay R.M., Pelletier G.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Bidwell C.A., Ji S., Frank G.R., Cornelius S.G., Willis G.M.,
RA Spurlock M.E.;
RT "Cloning and expression of the porcine obese gene.";
RL Anim. Biotechnol. 8:191-206(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9498356; DOI=10.2527/1998.762484x;
RA Ramsay T.G., Yan X., Morrison C.;
RT "The obesity gene in swine: sequence and expression of porcine leptin.";
RL J. Anim. Sci. 76:484-490(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Meishan;
RX PubMed=11147346;
RA Dai R.J., Li N., Wu C.X.;
RT "Molecular cloning and analysing of porcine obese cDNA.";
RL Yi Chuan Xue Bao 27:290-297(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA McNeel R.L., Mersmann H.J.;
RT "Adipose tissue regulatory transcript expression in lean versus obese
RT pigs.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Large white;
RA Soares M.A.M., Euclydes R.F., Guimaraes S.E.F., Martins M.F., Lopes P.S.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-110.
RC TISSUE=White adipose tissue;
RX PubMed=8856925; DOI=10.1111/j.1365-2052.1996.tb00489.x;
RA Neuenschwander S., Rettenberger G., Meijerink E., Jorg H., Stranzinger G.;
RT "Partial characterization of porcine obesity gene (OBS) and its
RT localization to chromosome 18 by somatic cell hybrids.";
RL Anim. Genet. 27:275-278(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; U63540; AAB05923.1; -; mRNA.
DR EMBL; AF026976; AAB82724.1; -; mRNA.
DR EMBL; U66254; AAB97308.1; -; Genomic_DNA.
DR EMBL; U59894; AAB03458.1; -; mRNA.
DR EMBL; AF052691; AAC06303.1; -; mRNA.
DR EMBL; AF102856; AAC78147.1; -; mRNA.
DR EMBL; AF477387; AAL84792.1; -; Genomic_DNA.
DR EMBL; AF477386; AAL84792.1; JOINED; Genomic_DNA.
DR EMBL; U40812; AAC48641.1; -; mRNA.
DR RefSeq; NP_999005.1; NM_213840.1.
DR AlphaFoldDB; Q29406; -.
DR SMR; Q29406; -.
DR STRING; 9823.ENSSSCP00000017572; -.
DR PaxDb; Q29406; -.
DR PRIDE; Q29406; -.
DR Ensembl; ENSSSCT00005065463; ENSSSCP00005040470; ENSSSCG00005040907.
DR Ensembl; ENSSSCT00030091214; ENSSSCP00030041970; ENSSSCG00030065266.
DR Ensembl; ENSSSCT00040071649; ENSSSCP00040030575; ENSSSCG00040052956.
DR Ensembl; ENSSSCT00045012944; ENSSSCP00045008914; ENSSSCG00045007725.
DR Ensembl; ENSSSCT00055053704; ENSSSCP00055042849; ENSSSCG00055027178.
DR Ensembl; ENSSSCT00060081608; ENSSSCP00060035345; ENSSSCG00060059821.
DR Ensembl; ENSSSCT00070056580; ENSSSCP00070048071; ENSSSCG00070028207.
DR GeneID; 396832; -.
DR KEGG; ssc:396832; -.
DR CTD; 3952; -.
DR eggNOG; ENOG502S5K5; Eukaryota.
DR HOGENOM; CLU_132715_0_0_1; -.
DR InParanoid; Q29406; -.
DR TreeFam; TF105086; -.
DR Reactome; R-SSC-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 18.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0051428; F:peptide hormone receptor binding; IBA:GO_Central.
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; IEA:Ensembl.
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:0006112; P:energy reserve metabolic process; IBA:GO_Central.
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:0006629; P:lipid metabolic process; IBA:GO_Central.
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:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:CACAO.
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:0032868; P:response to insulin; ISS:AgBase.
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; 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 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_0000017689"
FT DISULFID 117..167
FT /evidence="ECO:0000250"
FT CONFLICT 21..22
FT /note="AV -> GP (in Ref. 8; AAC48641)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="I -> L (in Ref. 8; AAC48641)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="A -> R (in Ref. 3; AAB97308)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 167 AA; 18661 MW; 27550E1E0E63814E CRC64;
MRCGPLCRFL WLWPYLSYVE AVPIWRVQDD TKTLIKTIVT RISDISHMQS VSSKQRVTGL
DFIPGLHPVL SLSKMDQTLA IYQQILTSLP SRNVIQISND LENLRDLLHL LASSKSCPLP
QARALETLES LGGVLEASLY STEVVALSRL QGALQDMLRQ LDLSPGC
