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leptin receptor; LEP-R; OB receptor; OB-R; HuB219; CD295 (LEPR, DB, OBR)

Function: - receptor for leptin (obesity factor) - on ligand binding, mediates signaling through JAK2/STAT3 - role in regulation of fat metabolism &, in a hematopoietic pathway, required for normal lymphopoiesis - may play a role in reproduction - able to mediate the ERK/FOS signaling pathway (putative) - on leptin stimulation, homodimerizes - on leptin binding, phosphorylated on 2 conserved C-terminal Tyr (isoform B only) by JAK2 - phosphorylated receptor binds a number of SH2 domain- containing proteins including STAT3, PTPN11, & SOCS3 (putative) - interaction with SOCS3 inhibits LRb signaling (putative) - Tyr-986 is required for complete binding & activation of PTPN11, ERK/FOS activation &, for interaction with SOCS3 (putative) - phosphorylation on Tyr-1141 is required for STAT3 binding & activation Structure: - cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase & STATs - WSXWS motif appears to be necessary for proper protein folding & thus efficient intracellular transport & cell-surface receptor binding - box 1 motif is required for JAK interaction &/or activation - belongs to the type I cytokine receptor family, type 2 subfamily - contains 4 fibronectin F3 modules - contains 1 Ig-like (immunoglobulin-like) domain Compartment: - cell membrane - isoform E: secreted (probable) Alternative splicing: named isoforms=5; A-E Expression: - isoform A is expressed in fetal liver & in hematopoietic tissues & choroid plexus - in adults highest expression in heart, liver, small intestine, prostate & ovary - low level in lung & kidney - isoform B is highly expressed in hypothalamus - arcuate nucleus of hypothalamus [2] - POMC & neuropeptide Y neurons Pathology: - ob (leptin) receptor gene mutation associated with autosomal recessive obesity Notes: - leptin increases frequency of action potentials in POMC neurons by - depolarization through nonspecific cation channel - reduced inhibition by neuropeptide-Y/GABA neurons [2]

Related

leptin receptor gene-related protein; leptin receptor overlapping transcript protein; OB-R gene-related protein; OB-RGRP (LEPROT, LEPR, OBR) leptin receptor overlapping transcript-like 1; brain my047 protein (LEPROTL1) leptin; obesity factor; obese protein (LEP, OB, OBS)

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen cytokine receptor glycoprotein

Properties

SIZE: entity length = 1165 aa MW = 132 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-21} N-glycosylation site {N23} cysteine residue {C37} MODIFICATION: cysteine residue {C90} N-glycosylation site {N41} N-glycosylation site {N56} N-glycosylation site {N73} N-glycosylation site {N81} cysteine residue {C89} MODIFICATION: cysteine residue {C99} cysteine residue {C90} MODIFICATION: cysteine residue {C37} N-glycosylation site {N98} cysteine residue {C99} MODIFICATION: cysteine residue {C89} cysteine residue {C131} MODIFICATION: cysteine residue {C142} cysteine residue {C142} MODIFICATION: cysteine residue {C131} cysteine residue {C186} MODIFICATION: cysteine residue {C196} N-glycosylation site {N187} cysteine residue {C188} MODIFICATION: cysteine residue {C193} cysteine residue {C193} MODIFICATION: cysteine residue {C188} cysteine residue {C196} MODIFICATION: cysteine residue {C186} N-glycosylation site {N206} fibronectin type III domain or F3 module {237-330} MOTIF: N-glycosylation site {N276} immunoglobulin superfamily domain {325-429} MOTIF: N-glycosylation site {N347} cysteine residue {C352} MODIFICATION: cysteine residue {C412} N-glycosylation site {N397} cysteine residue {C412} MODIFICATION: cysteine residue {C352} cysteine residue {C413} MODIFICATION: cysteine residue {C418} cysteine residue {C418} MODIFICATION: cysteine residue {C413} cysteine residue {C473} MODIFICATION: cysteine residue {C528} cysteine residue {C488} MODIFICATION: cysteine residue {C498} cysteine residue {C498} MODIFICATION: cysteine residue {C488} N-glycosylation site {N516} cysteine residue {C528} MODIFICATION: cysteine residue {C473} fibronectin type III domain or F3 module {537-631} MOTIF: WSXWS motif {622-626} N-glycosylation site {N624} fibronectin type III domain or F3 module {639-732} MOTIF: N-glycosylation site {N659} N-glycosylation site {N688} N-glycosylation site {N697} N-glycosylation site {N728} fibronectin type III domain or F3 module {734-829} MOTIF: N-glycosylation site {N750} transmembrane domain {840-862} box1 motif SITE: 871-879 FOR-BINDING-OF: Janus kinase (JAK) JAK2 activation {893-898} Tyr phosphorylation site {Y986} Tyr phosphorylation site {Y1141}

Database Correlations

OMIM 601007 UniProt P48357 PFAM correlations Entrez Gene 3953 Kegg hsa:3953

References

  1. Tartaglia LA et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263-71 1995 PMID: 8548812
  2. Cowley MA et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-4, 2001 PMID: 11373681
  3. UniProt :accession P48357