Tclin LEPR Leptin receptor

Protein Summary

Description

Receptor for hormone LEP/leptin (Probable) (PubMed:22405007). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (By similarity) (PubMed:9537324). In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity (PubMed:25060689, PubMed:12504075, PubMed:8805376). Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis. Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus. Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T -ells. Leptin increases Th1 and suppresses Th2 cytokine production (By similarity). Isoform A: May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3. Isoform E: Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis. The protein encoded by this gene belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymphopoiesis. Mutations in this gene have been associated with obesity and pituitary dysfunction. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. It is noteworthy that this gene and LEPROT gene (GeneID:54741) share the same promoter and the first 2 exons, however, encode distinct proteins (PMID:9207021).[provided by RefSeq, Nov 2010]

Uniprot Accession IDs

• P48357
• Q13592
• Q13593
• Q13594
• Q92919
• Q92920
• Q92921
• LEP-R

Gene Name

• LEPR

Ensembl ID

• ENST00000344610
• ENSP00000340884
• ENSG00000116678
• ENST00000349533
• ENSP00000330393
• ENST00000371058
• ENSP00000360097
• ENST00000371059
• ENSP00000360098
• ENST00000371060
• ENSP00000360099
• ENST00000616738
• ENSP00000483390

Symbol

• DB
• OBR
• OBR
• OB-R
• CD295
• LEP-R
• LEPRD

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	0.93
protein domain	0.92
trait	0.75
transcription factor binding site profile	0.75
PubMedID	0.74

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Leptin Receptor

Protein / Defense/immunity Protein / Leptin Receptor

DTO Classes

Protein / Signaling / Cytokine / Leptin Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1091.02   (req: < 5)

Gene RIFs: 572   (req: <= 3)

Antibodies: 834   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1091.02   (req: >= 5)

Gene RIFs: 572   (req: > 3)

Antibodies: 834   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 25

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1