FUNCTION: SwissProt: P48357 # Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lymphopoiesis. May play a role in reproduction. Can also mediate the ERK/FOS signaling pathway (By similarity).
SIZE: 1165 amino acids; 132494 Da
SUBUNIT: On leptin stimulation, homodimerizes. The phosphorylated receptor binds a number of SH2 domain-containing proteins such as STAT3, PTPN11, and SOCS3 (By similarity). Interaction with SOCS3 inhibits LRb signaling (By similarity).
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. & Isoform E: Secreted (Probable).
TISSUE SPECIFICITY: 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.
DOMAIN: SwissProt: P48357 The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs. & The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding. & 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 and, for interaction with SOCS3 (By similarity). Phosphorylation on Tyr-1141 is required for STAT3 binding/activation.
SIMILARITY: Belongs to the type I cytokine receptor family. Type 2 subfamily. & Contains 4 fibronectin type-III domains. & Contains 1 Ig-like (immunoglobulin-like) domain.