Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Lep. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is secreted by white adipocytes, and which plays a major role in the regulation of body weight. This protein, which acts through the leptin receptor, functions as part of a signaling pathway that can inhibit food intake and/or regulate energy expenditure to maintain constancy of the adipose mass. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis and wound healing. Mutations in this gene and/or its regulatory regions cause severe obesity, and morbid obesity with hypogonadism. This gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Lep
  • participates in the following biological processes:
    • adult feeding behavior ^[6]
    • bile acid metabolic process ^[4]
    • negative regulation of appetite ^[6]
    • negative regulation of glucagon secretion ^[11]
    • negative regulation of transcription from RNA polymerase II promoter ^[11]
    • positive regulation of JAK-STAT cascade ^[11]
    • positive regulation of myeloid cell differentiation ^[12]
    • positive regulation of protein import into nucleus ^[11]
    • positive regulation of STAT protein import into nucleus ^[11]
    • regulation of intestinal cholesterol absorption ^[4]
    • regulation of protein phosphorylation ^[11]
    • tyrosine phosphorylation of STAT protein ^[11]
  • performs the following molecular functions:
    • growth factor activity ^[12]
  • is located in the following cellular components:
    • extracellular space ^{[6, 7, 14]}
• The gene product of Lep has been shown to bind to the gene products of Leprot. ^[16]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Lep
  • participates in the following biological processes:
    • central nervous system neuron development ^[8]
    • glucose metabolic process ^[10]
    • hormone metabolic process ^[9]
    • lipid metabolic process ^[13]
    • regulation of gluconeogenesis ^[9]
    • regulation of insulin secretion ^[9]
    • regulation of metabolic process ^[5]
    • regulation of steroid biosynthetic process ^[9]
    • response to dietary excess ^[17]
    • response to insulin stimulus ^[17]
• Researchers have inferred, based on genetic interactions, that the gene product of Lep
  • participates in the following biological processes:
    • adipose tissue development based on interactions with Hmga2 ^[1]
    • cholesterol metabolic process based on interactions with Apoa1 ^[2]
    • eating behavior based on interactions with Th ^[15]
    • insulin secretion based on interactions with Vgf ^[17]
    • response to dietary excess based on interactions with Vgf ^[3]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Lep:
  • participates in the following biological processes:
    • bone mineralization involved in bone maturation
    • energy reserve metabolic process
    • fatty acid catabolic process
    • glycerol biosynthetic process
    • intracellular signal transduction
    • leptin-mediated signaling pathway
    • leukocyte tethering or rolling
    • negative regulation of apoptotic process
    • negative regulation of cartilage development
    • negative regulation of glutamine transport
    • negative regulation of metabolic process
    • negative regulation of vasoconstriction
    • ovulation from ovarian follicle
    • placenta development
    • positive regulation of cell proliferation
    • positive regulation of developmental growth
    • positive regulation of hepatic stellate cell activation
    • positive regulation of insulin receptor signaling pathway
    • positive regulation of ion transport
    • positive regulation of JAK-STAT cascade
    • positive regulation of MAPK cascade
    • positive regulation of tyrosine phosphorylation of Stat3 protein
    • regulation of blood pressure
    • regulation of lipoprotein lipid oxidation
    • response to dietary excess
  • performs the following molecular functions:
    • hormone activity
    • peptide hormone receptor binding
  • is located in the following cellular components:
    • extracellular space
    • intracellular

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Summary text based on GO annotations supported by structural data

• Lep encodes a protein or proteins that contain the following InterPro domains: Four-helical cytokine, core, Four-helical cytokine-like, core, Obesity factor, indicating that the gene product:
  • participates in the following biological processes:
    • signal transduction
  • is located in the following cellular components:
    • extracellular region

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Lep indicates that it:
  • is located in the following cellular components:
    • extracellular region

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References

1. Anand A et al. (2000) In vivo modulation of Hmgic reduces obesity. Nat Genet, 24:377-80. (PubMed:10742101)
2. Gruen ML et al. (2005) Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. J Lipid Res, 46:2007-14. (PubMed:15995171)
3. Hahm S et al. (2002) VGF is required for obesity induced by diet, gold thioglucose treatment, and agouti and is differentially regulated in pro-opiomelanocortin- and neuropeptide Y-containing arcuate neurons in response to fasting. J Neurosci, 22:6929-38. (PubMed:12177191)
4. Hyogo H et al. (2002) Leptin Promotes Biliary Cholesterol Elimination during Weight Loss in ob/ob Mice by Regulating the Enterohepatic Circulation of Bile Salts. J Biol Chem, 277:34117-24. (PubMed:12114517)
5. Ishii M et al. (2003) Targeted disruption of GPR7, the endogenous receptor for neuropeptides B and W, leads to metabolic defects and adult-onset obesity. Proc Natl Acad Sci U S A, 100:10540-5. (PubMed:12925742)
6. Kristensen P et al. (1998) Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature, 393:72-6. (PubMed:9590691)
7. Lee NK et al. (2007) Endocrine regulation of energy metabolism by the skeleton. Cell, 130:456-69. (PubMed:17693256)
8. Li N et al. (1999) NMDA and AMPA glutamate receptor subtypes in the thoracic spinal cord in lean and obese-diabetic ob/ob mice. Brain Res, 849:34-44. (PubMed:10592285)
9. Luque RM et al. (2006) Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function. Endocrinology, 147:2754-63. (PubMed:16513828)
10. Maeda K et al. (2003) Role of the fatty acid binding protein mal1 in obesity and insulin resistance. Diabetes, 52:300-7. (PubMed:12540600)
11. Marroqui L et al. (2011) Leptin downregulates expression of the gene encoding glucagon in alphaTC1-9 cells and mouse islets. Diabetologia, null:null. (PubMed:21234744)
12. Mikhail AA et al. (1997) Leptin stimulates fetal and adult erythroid and myeloid development. Blood, 89:1507-12. (PubMed:9057630)
13. Miyazaki M et al. (2003) Identification and characterization of murine SCD4, a novel heart-specific stearoyl-CoA desaturase isoform regulated by leptin and dietary factors. J Biol Chem, 278:33904-11. (PubMed:12815040)
14. Peterson JM et al. (2010) C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output. J Biol Chem, 285:39691-701. (PubMed:20952387)
15. Szczypka MS et al. (2000) Dopamine is required for hyperphagia in Lep(ob/ob) mice. Nat Genet, 25:102-4. (PubMed:10802666)
16. Tartaglia LA. (1997) The leptin receptor. J Biol Chem, 272:6093-6. (PubMed:9102398)
17. Watson E et al. (2005) VGF ablation blocks the development of hyperinsulinemia and hyperglycemia in several mouse models of obesity. Endocrinology, 146:5151-63. (PubMed:16141392)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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