Q62959 · LEPR_RAT
- ProteinLeptin receptor
- GeneLepr
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1162 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Receptor for hormone LEP/leptin (Probable). 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 (PubMed:8690163).
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 (By similarity).
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-cells. Leptin increases Th1 and suppresses Th2 cytokine production (By similarity).
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 (By similarity).
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-cells. 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 (PubMed:10698121).
Does not induce phosphorylation of and activate STAT3 (By similarity).
Does not induce phosphorylation of and activate STAT3 (By similarity).
Isoform E
Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.
GO annotations
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameLeptin receptor
- Short namesLEP-R
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ62959
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Isoform E
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 22-839 | Extracellular | ||||
Sequence: LNLAYPTSPWRFKLFCAPPSTTDDSFLSPAGVPNNTSSLKGASEALVEAKFNSTGIYVSELSKTIFHCCFGNEQGQNCSALTGNTEGKTLASVVKPLVFRQLGVNWDIECWMKGDLTLFICHMEPLLKNPFKNYDSKVHLLYDLPEVIDDLPLPPLKDSFQTVQCNCSVRECECHVPVPRAKVNYALLMYLEITSAGVSFQSPLMSLQPMLVVKPDPPLGLRMEVTDDGNLKISWDSQTKAPFPLQYQVKYLENSTIVREAAEIVSDTSLLVDSVLPGSSYEVQVRSKRLDGSGVWSDWSLPQLFTTQDVMYFPPKILTSVGSNASFCCIYKNENQTISSKQIVWWMNLAEKIPETQYNTVSDHISKVTFSNLKATRPRGKFTYDAVYCCNEQACHHRYAELYVIDVNINISCETDGYLTKMTCRWSPSTIQSLVGSTVQLRYHRRSLYCPDNPSIRPTSELKNCVLQTDGFYECVFQPIFLLSGYTMWIRINHSLGSLDSPPTCVLPDSVVKPLPPSNVKAEITINTGLLKVSWEKPVFPENNLQFQIRYGLNGKEIQWKTHEVFDAKSKSASLPVSDLCAVYVVQVRCRRLDGLGYWSNWSSPAYTLVMDVKVPMRGPEFWRIMDGDITKKERNVTLLWKPLMKNDSLCSVRRYVVKHRTAHNGTWSQDVGNQTNLTFLWAESAHTVTVLAINSIGASLVNFNLTFSWPMSKVNAVQSLSAYPLSSSCVILSWTLSPNDYSLLYLVIEWKNLNDDDGMKWLRIPSNVNKYYIHDNFIPIEKYQFSLYPVFMEGVGKPKIINGFTKDDIAKQQNDAG | ||||||
Transmembrane | 840-860 | Helical | ||||
Sequence: LYVIVPIIISSCVLLLGTLLI | ||||||
Topological domain | 861-1162 | Cytoplasmic | ||||
Sequence: SHQRMKKLFWDDVPNPKNCSWAQGLNFQKPETFEHLFTKHAESVIFGPLLLEPEPVSEEISVDTAWKNKDEMVPAAMVSLLLTTPDSTRGSICISDQCNSANFSGAQSTQGTCEDECQSQPSVKYATLVSNVKTVETDEEQGAIHSSVSQCIARKHSPLRQSFSSNSWEIEAQAFFLLSDHPPNVISPQLSFSGLDELLELEGNFPEENHGEKSVYYLGVSSGNKRENDMLLTDEAGVLCPFPAHCLFSDIRILQESCSHFVENNLNLGTSGKNFVPYMPQFQSCSTHSHKIIENKMCDLTV |
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 269 | in FA | ||||
Sequence: Q → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MTCQKFYVVLLHWEFLYVITA | ||||||
Chain | PRO_0000010908 | 22-1162 | Leptin receptor | |||
Sequence: LNLAYPTSPWRFKLFCAPPSTTDDSFLSPAGVPNNTSSLKGASEALVEAKFNSTGIYVSELSKTIFHCCFGNEQGQNCSALTGNTEGKTLASVVKPLVFRQLGVNWDIECWMKGDLTLFICHMEPLLKNPFKNYDSKVHLLYDLPEVIDDLPLPPLKDSFQTVQCNCSVRECECHVPVPRAKVNYALLMYLEITSAGVSFQSPLMSLQPMLVVKPDPPLGLRMEVTDDGNLKISWDSQTKAPFPLQYQVKYLENSTIVREAAEIVSDTSLLVDSVLPGSSYEVQVRSKRLDGSGVWSDWSLPQLFTTQDVMYFPPKILTSVGSNASFCCIYKNENQTISSKQIVWWMNLAEKIPETQYNTVSDHISKVTFSNLKATRPRGKFTYDAVYCCNEQACHHRYAELYVIDVNINISCETDGYLTKMTCRWSPSTIQSLVGSTVQLRYHRRSLYCPDNPSIRPTSELKNCVLQTDGFYECVFQPIFLLSGYTMWIRINHSLGSLDSPPTCVLPDSVVKPLPPSNVKAEITINTGLLKVSWEKPVFPENNLQFQIRYGLNGKEIQWKTHEVFDAKSKSASLPVSDLCAVYVVQVRCRRLDGLGYWSNWSSPAYTLVMDVKVPMRGPEFWRIMDGDITKKERNVTLLWKPLMKNDSLCSVRRYVVKHRTAHNGTWSQDVGNQTNLTFLWAESAHTVTVLAINSIGASLVNFNLTFSWPMSKVNAVQSLSAYPLSSSCVILSWTLSPNDYSLLYLVIEWKNLNDDDGMKWLRIPSNVNKYYIHDNFIPIEKYQFSLYPVFMEGVGKPKIINGFTKDDIAKQQNDAGLYVIVPIIISSCVLLLGTLLISHQRMKKLFWDDVPNPKNCSWAQGLNFQKPETFEHLFTKHAESVIFGPLLLEPEPVSEEISVDTAWKNKDEMVPAAMVSLLLTTPDSTRGSICISDQCNSANFSGAQSTQGTCEDECQSQPSVKYATLVSNVKTVETDEEQGAIHSSVSQCIARKHSPLRQSFSSNSWEIEAQAFFLLSDHPPNVISPQLSFSGLDELLELEGNFPEENHGEKSVYYLGVSSGNKRENDMLLTDEAGVLCPFPAHCLFSDIRILQESCSHFVENNLNLGTSGKNFVPYMPQFQSCSTHSHKIIENKMCDLTV | ||||||
Disulfide bond | 37↔90 | |||||
Sequence: CAPPSTTDDSFLSPAGVPNNTSSLKGASEALVEAKFNSTGIYVSELSKTIFHCC | ||||||
Glycosylation | 55 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 56 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 73 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 89↔99 | |||||
Sequence: CCFGNEQGQNC | ||||||
Glycosylation | 98 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 131↔142 | |||||
Sequence: CWMKGDLTLFIC | ||||||
Disulfide bond | 186↔195 | |||||
Sequence: CNCSVRECEC | ||||||
Glycosylation | 187 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 188↔193 | |||||
Sequence: CSVREC | ||||||
Glycosylation | 275 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 345 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 350↔410 | |||||
Sequence: CIYKNENQTISSKQIVWWMNLAEKIPETQYNTVSDHISKVTFSNLKATRPRGKFTYDAVYC | ||||||
Glycosylation | 356 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 411↔416 | |||||
Sequence: CNEQAC | ||||||
Glycosylation | 431 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 434↔445 | |||||
Sequence: CETDGYLTKMTC | ||||||
Disulfide bond | 471↔526 | |||||
Sequence: CPDNPSIRPTSELKNCVLQTDGFYECVFQPIFLLSGYTMWIRINHSLGSLDSPPTC | ||||||
Disulfide bond | 486↔496 | |||||
Sequence: CVLQTDGFYEC | ||||||
Glycosylation | 514 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 622 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 657 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 668 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 686 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 695 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 698 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 726 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 880 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 985 | Phosphotyrosine; by JAK2 | ||||
Sequence: Y | ||||||
Modified residue | 1077 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1138 | Phosphotyrosine; by JAK2 | ||||
Sequence: Y |
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,for interaction with SOCS3 and SOCS3 mediated inhibition of leptin signaling. Phosphorylation on Tyr-1138 is required for STAT3 binding/activation. Phosphorylation of Tyr-1077 has a more accessory role.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Isoform B is expressed in kidney, liver, lung, ovary, spleen and uterus. Increased level in uterus during gestation (PubMed:8772180).
Isoform A and isoform C are predominantly expressed in cerebral microvessels and choroid plexus, with lower levels in cortex, cerebellum and hypothalamus but also liver and lung (PubMed:11861497).
Isoform F is expressed at high levels in brain, liver and spleen and less in stomach, kidney, thymus, heart, lung and hypothalamus (PubMed:11861497, PubMed:8772180).
Isoform A and isoform C are predominantly expressed in cerebral microvessels and choroid plexus, with lower levels in cortex, cerebellum and hypothalamus but also liver and lung (PubMed:11861497).
Isoform F is expressed at high levels in brain, liver and spleen and less in stomach, kidney, thymus, heart, lung and hypothalamus (PubMed:11861497, PubMed:8772180).
Interaction
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).
Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (By similarity).
Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 238-331 | Fibronectin type-III 1 | ||||
Sequence: PPLGLRMEVTDDGNLKISWDSQTKAPFPLQYQVKYLENSTIVREAAEIVSDTSLLVDSVLPGSSYEVQVRSKRLDGSGVWSDWSLPQLFTTQDV | ||||||
Region | 465-482 | Leptin-binding | ||||
Sequence: HRRSLYCPDNPSIRPTSE | ||||||
Domain | 537-632 | Fibronectin type-III 2 | ||||
Sequence: PPSNVKAEITINTGLLKVSWEKPVFPENNLQFQIRYGLNGKEIQWKTHEVFDAKSKSASLPVSDLCAVYVVQVRCRRLDGLGYWSNWSSPAYTLVM | ||||||
Motif | 620-624 | WSXWS motif | ||||
Sequence: WSNWS | ||||||
Domain | 637-729 | Fibronectin type-III 3 | ||||
Sequence: PMRGPEFWRIMDGDITKKERNVTLLWKPLMKNDSLCSVRRYVVKHRTAHNGTWSQDVGNQTNLTFLWAESAHTVTVLAINSIGASLVNFNLTF | ||||||
Domain | 738-831 | Fibronectin type-III 4 | ||||
Sequence: AVQSLSAYPLSSSCVILSWTLSPNDYSLLYLVIEWKNLNDDDGMKWLRIPSNVNKYYIHDNFIPIEKYQFSLYPVFMEGVGKPKIINGFTKDDI | ||||||
Motif | 869-877 | Box 1 motif | ||||
Sequence: FWDDVPNPK | ||||||
Region | 891-896 | Required for JAK2 activation | ||||
Sequence: ETFEHL | ||||||
Region | 896-904 | Required for STAT3 phosphorylation | ||||
Sequence: LFTKHAESV |
Domain
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.
Sequence similarities
Belongs to the type I cytokine receptor family. Type 2 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 6 isoforms produced by Alternative splicing.
Q62959-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameB
- Length1,162
- Mass (Da)130,833
- Last updated1996-11-01 v1
- ChecksumBA7AC2CA2D2E62AF
Q62959-2
- NameA
Q62959-3
- NameC
Q62959-6
- NameD
Q62959-4
- NameE
Q62959-5
- NameF
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AJP1 | A0A8I6AJP1_RAT | Lepr | 894 | ||
F1M9F2 | F1M9F2_RAT | Lepr | 895 | ||
A0A8I5ZQD9 | A0A8I5ZQD9_RAT | Lepr | 1162 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 2 | in Ref. 4; AAB06616 | ||||
Sequence: T → M | ||||||
Sequence conflict | 12 | in Ref. 8; BAA24899 | ||||
Sequence: H → P | ||||||
Sequence conflict | 34 | in Ref. 8; BAA24899 | ||||
Sequence: K → R | ||||||
Sequence conflict | 415-417 | in Ref. 7; AAB03088 | ||||
Sequence: ACH → QCQ | ||||||
Sequence conflict | 422 | in Ref. 7; AAB03088 | ||||
Sequence: E → D | ||||||
Sequence conflict | 493 | in Ref. 7; AAB03088 | ||||
Sequence: F → L | ||||||
Sequence conflict | 498 | in Ref. 7; AAB03088 | ||||
Sequence: F → S | ||||||
Sequence conflict | 612 | in Ref. 7; AAB03088 | ||||
Sequence: R → Q | ||||||
Sequence conflict | 690 | in Ref. 7; AAB03088 | ||||
Sequence: S → T | ||||||
Sequence conflict | 703-704 | in Ref. 7; AAB03088 | ||||
Sequence: WA → SG | ||||||
Sequence conflict | 714 | in Ref. 7; AAB03088 | ||||
Sequence: A → D | ||||||
Sequence conflict | 738-739 | in Ref. 7; AAB03088 | ||||
Sequence: AV → GW | ||||||
Sequence conflict | 751-752 | in Ref. 10; AAB40654 | ||||
Sequence: CV → SL | ||||||
Sequence conflict | 766 | in Ref. 9; AAB63202 | ||||
Sequence: L → S | ||||||
Sequence conflict | 785 | in Ref. 9; AAB63202 | ||||
Sequence: R → K | ||||||
Sequence conflict | 794 | in Ref. 9; AAB63202 | ||||
Sequence: Y → N | ||||||
Alternative sequence | VSP_001709 | 797-805 | in isoform E | |||
Sequence: DNFIPIEKY → GMCTVLLLN | ||||||
Alternative sequence | VSP_001710 | 806-1162 | in isoform E | |||
Sequence: Missing | ||||||
Sequence conflict | 846 | in Ref. 9; AAB63201 | ||||
Sequence: I → V | ||||||
Alternative sequence | VSP_001707 | 890-892 | in isoform C | |||
Sequence: PET → VTV | ||||||
Alternative sequence | VSP_001705 | 890-894 | in isoform A | |||
Sequence: PETFE → RADTL | ||||||
Alternative sequence | VSP_001711 | 890-895 | in isoform F | |||
Sequence: PETFEH → IMPGRN | ||||||
Alternative sequence | VSP_001708 | 893-1162 | in isoform C | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_001706 | 895-1162 | in isoform A | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_001712 | 896-1162 | in isoform F | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U52966 EMBL· GenBank· DDBJ | AAC52587.1 EMBL· GenBank· DDBJ | mRNA | ||
D84550 EMBL· GenBank· DDBJ | BAA12697.1 EMBL· GenBank· DDBJ | mRNA | ||
D84551 EMBL· GenBank· DDBJ | BAA12698.1 EMBL· GenBank· DDBJ | mRNA | ||
D85557 EMBL· GenBank· DDBJ | BAA12830.1 EMBL· GenBank· DDBJ | mRNA | ||
D85558 EMBL· GenBank· DDBJ | BAA12831.1 EMBL· GenBank· DDBJ | mRNA | ||
D85559 EMBL· GenBank· DDBJ | BAA12832.1 EMBL· GenBank· DDBJ | mRNA | ||
U60151 EMBL· GenBank· DDBJ | AAB06616.1 EMBL· GenBank· DDBJ | mRNA | ||
D84125 EMBL· GenBank· DDBJ | BAA12230.1 EMBL· GenBank· DDBJ | mRNA | ||
D84126 EMBL· GenBank· DDBJ | BAA12231.1 EMBL· GenBank· DDBJ | mRNA | ||
AF287268 EMBL· GenBank· DDBJ | AAF89300.1 EMBL· GenBank· DDBJ | mRNA | ||
U53144 EMBL· GenBank· DDBJ | AAB03088.1 EMBL· GenBank· DDBJ | mRNA | ||
AB011006 EMBL· GenBank· DDBJ | BAA24899.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF007818 EMBL· GenBank· DDBJ | AAB63201.1 EMBL· GenBank· DDBJ | mRNA | ||
AF007819 EMBL· GenBank· DDBJ | AAB63202.1 EMBL· GenBank· DDBJ | mRNA | ||
U67207 EMBL· GenBank· DDBJ | AAB40654.1 EMBL· GenBank· DDBJ | mRNA | ||
AF304191 EMBL· GenBank· DDBJ | AAG22823.1 EMBL· GenBank· DDBJ | mRNA |