Function: 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.Isoform A may act to transport leptin to the cerebrospinal fluid
By similarity.Isoform E could function as a transport protein.
Subunit structure: On leptin stimulation, homodimerizes. The phosphorylated receptor binds a number of SH2 domain-containing proteins such as STAT3, PTPN11, and SOCS3. Interaction with SOCS3 inhibits JAK/STAT signaling.
Subcellular location: Cell membrane; Single-pass type I membrane protein. Isoform E: Secreted
Probable.
Tissue specificity: Isoform A:highest level of expression in lung and kidney, also present in kidney, heart, brain, spleen, liver, muscle, choroid plexus and hypothalamus. Isoform B:highest level of expression in hypothalamus and lower level in brain, testes and adipose tissue. Isoform E:expressed in adipose tissue, hypothalamus, heart, and testes.
Domain: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. Ref.13The box 1 motif is required for JAK interaction and/or activation. Ref.13
Post-translational modification: On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-985 is required for complete binding and activation of PTPN11, ERK/FOS activation and, for interaction with SOCS3. Phosphorylation on Tyr-1138 is required for STAT3 binding/activation. Ref.10 Ref.11Phosphorylation of Tyr-985 is required for SOCS3 binding and SOCS3 mediated inhibition of leptin signaling, whereas phosphorylation of Tyr-1077 has a more accessory role.
Sequence similarities: Belongs to the type I cytokine receptor family. Type 2 subfamily.Contains 4 fibronectin type-III domains.Contains 1 Ig-like (immunoglobulin-like) domain.
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