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Details on Person UniProt:P48357-1 LEPR
| Class:Id | ReferenceIsoform:404134 |
|---|---|
| _chainChangeLog | signal peptide:1-21 added on Fri February 6 2015;chain:22-1165 added on Fri February 6 2015 |
| _displayName | UniProt:P48357-1 LEPR |
| _timestamp | 2024-11-03 19:41:40 |
| chain | signal peptide:1-21 chain:22-1165 |
| checksum | CAA03BEAF2602D0A |
| comment | FUNCTION 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:12504075, PubMed:25060689, 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).FUNCTION May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3.FUNCTION Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.SUBUNIT Present as a mixture of monomers and dimers (Probable). The phosphorylated receptor binds a number of SH2 domain-containing proteins such as JAK2, STAT3, PTPN11, and SOCS3 (By similarity) (PubMed:9600917). Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (By similarity).INTERACTION Isoform A is expressed in fetal liver and in hematopoietic tissues and choroid plexus. In adults highest expression in heart, liver, small intestine, prostate and ovary. Low level in lung and kidney. Isoform B is highly expressed in hypothalamus, but also in skeletal muscle. Detected in fundic and antral epithelial cells of the gastric mucosa (PubMed:19159218). Isoform B and isoform A are expressed by NK cells (at protein level) (PubMed:12504075).DOMAIN The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs.DOMAIN The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.DOMAIN The box 1 motif is required for JAK interaction and/or activation.PTM On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-986 is required for complete binding and activation of PTPN11, ERK/FOS activation,for interaction with SOCS3 and SOCS3 mediated inhibition of leptin signaling. Phosphorylation on Tyr-1141 is required for STAT3 binding/activation. Phosphorylation of Tyr-1079 has a more accessory role.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the type I cytokine receptor family. Type 2 subfamily. |
| created | [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 |
| description | recommendedName: Leptin receptor shortName: LEP-R alternativeName: HuB219 alternativeName: OB receptor shortName: OB-R cdAntigenNameCD295/cdAntigenName |
| geneName | LEPR DB OBR |
| identifier | P48357 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell membrane Direct protein sequencing Disulfide bond Glycoprotein Immunoglobulin domain Membrane Obesity Phosphoprotein Proteomics identification Receptor Reference proteome Repeat Secreted Signal Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | LEPR |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8996061] ENSEMBL:ENSG00000116678 LEPR [Homo sapiens] |
| secondaryIdentifier | LEPR_HUMAN Q13592 Q13593 Q13594 Q92919 Q92920 Q92921 |
| sequenceLength | 1165 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P48357-1 |
| (referenceEntity) | [EntityWithAccessionedSequence:2586513] p-Y986,Y1079,Y1141-LEPR-1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2586526] LEPR-1 [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:2586534] O4'-phospho-L-tyrosine at 1141 [ModifiedResidue:2586537] O4'-phospho-L-tyrosine at 1079 [ModifiedResidue:2586543] O4'-phospho-L-tyrosine at 986 |
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No pathways have been reviewed or authored by UniProt:P48357-1 LEPR (404134)
