Reactome | UniProt:P48356-1 Lepr

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UniProt:P48356-1 Lepr Show undefined attributes

chain	signal peptide:1-21 chain:22-1162
checksum	0E1E75B076BA60A2
comment	FUNCTION Receptor for hormone LEP/leptin (Probable) (PubMed:11861497). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS (PubMed:10799542, PubMed:11861497, PubMed:11923481, PubMed:25383904). 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:10660043, PubMed:12594516). 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:11923481, PubMed:25383904). 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 (PubMed:12594516). Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus (PubMed:25383904). 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 (PubMed:9732873).FUNCTION May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis (PubMed:17620316, PubMed:20223942). Does not induce phosphorylation of and activate STAT3 (PubMed:11923481, PubMed:20223942).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:11018044, PubMed:11923481). Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (PubMed:11018044).INTERACTION Isoform A: highest level of expression in lung and kidney, also present in heart, brain, spleen, liver, muscle, choroid plexus and hypothalamus. Isoform B: highest levels of expression in hypothalamus and lower levels in brain, testes and adipose tissue. Expressed by neurons of the parabrachial nucleus (PubMed:25383904). Expressed by peripheral blood mononuclear cells and CD4(+) T-cells (PubMed:9732873). Isoform E: expressed in adipose tissue, liver, hypothalamus, cerebral microvessels, heart, and testes (PubMed:17620316).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-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.DISRUPTION PHENOTYPE Mutants are hyperphagic, obese, infertile, diabetic and have impaired growth (PubMed:12594516). Have wet brain weight significantly lower than controls. Brain uptake of leptin is also reduced (PubMed:11861497). Animals have an increased bone formation leading to high bone mass (PubMed:10660043). Have impaired T-cell immunity, Th2 responses are favoured in mutants (PubMed:9732873). Conditional knockout in parabrachial nucleus CCK-expressing neurons, treated with 2-deoxyglucose, have increased levels of glucagon, corticosterone and epinephrin concentrations compared to wild-types (PubMed:25383904).SIMILARITY Belongs to the type I cytokine receptor family. Type 2 subfamily.
created	[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
crossReference	[DatabaseIdentifier:12323966] RefSeq:NP_034834.1 [DatabaseIdentifier:12323965] RefSeq:NP_666258.2 [DatabaseIdentifier:12323964] RefSeq:NP_001116371.1 [DatabaseIdentifier:12246379] PRO:P48356 [DatabaseIdentifier:12186033] PDB:8AVD [DatabaseIdentifier:12186037] PDB:8DHA [DatabaseIdentifier:12186035] PDB:8AV2 [DatabaseIdentifier:12186036] PDB:8AVB [DatabaseIdentifier:12186034] PDB:8B7Q [DatabaseIdentifier:12186032] PDB:8AVC [DatabaseIdentifier:12186028] PDB:8DH8 [DatabaseIdentifier:12186029] PDB:8DH9 [DatabaseIdentifier:12186031] PDB:7Z3P [DatabaseIdentifier:12186030] PDB:7Z3R [DatabaseIdentifier:11936215] MGI:104993 [DatabaseIdentifier:11804115] GlyGen:P48356 [DatabaseIdentifier:11664156] ENSEMBL:ENSMUST00000037552 [DatabaseIdentifier:11664157] ENSEMBL:ENSMUST00000102777 [DatabaseIdentifier:11664158] ENSEMBL:ENSMUST00000106921 [DatabaseIdentifier:11541457] ENSEMBL:ENSMUSP00000099838 [DatabaseIdentifier:11541459] ENSEMBL:ENSMUSP00000037385 [DatabaseIdentifier:11541458] ENSEMBL:ENSMUSP00000102534 [DatabaseIdentifier:11451922] ENSEMBL:ENSMUSG00000057722
databaseName	UniProt
dbId	404133
description	recommendedName: Leptin receptor shortName: LEP-R alternativeName: B219 alternativeName: OB receptor shortName: OB-R cdAntigenNameCD295/cdAntigenName
displayName	UniProt:P48356-1 Lepr
geneName	Lepr Db Obr
identifier	P48356
isSequenceChanged	false
isoformParent	[ReferenceGeneProduct:uniprot:P48356] UniProt:P48356 Lepr
keyword	3D-structure Alternative splicing Cell membrane Disulfide bond Glycoprotein Immunoglobulin domain Membrane Obesity Phosphoprotein Receptor Reference proteome Repeat Secreted Signal Transmembrane Transmembrane helix
modified	[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
moleculeType	Protein
name	Lepr
otherIdentifier	100430_at 100431_at 10506301 1425644_at 1425873_a_at 1425875_a_at 1456156_at 16847 17415979 4328655 4336385 4342278 4354943 4366214 4376593 4419878 4424168 4439929 4439995 4440948 4517910 4523482 4524740 4527991 4562370 4590136 4614362 4616391 4634425 4665797 4746613 4772550 4774628 4828712 4890645 5074773 5140509 5205658 5215171 5231352 5273090 5276460 5370225 5420535 5457902 5555082 A_51_P396045 A_52_P247900 A_55_P2177910 A_55_P2177911 A_55_P2192662 A_55_P2506350 A_55_P2621144 A_55_P2621147 A_66_P130517 GO:0001525 GO:0002376 GO:0004888 GO:0004896 GO:0005515 GO:0005576 GO:0005886 GO:0005975 GO:0005977 GO:0006094 GO:0006629 GO:0006909 GO:0007165 GO:0008203 GO:0008284 GO:0009897 GO:0010507 GO:0014009 GO:0016020 GO:0016192 GO:0016323 GO:0017046 GO:0019221 GO:0019953 GO:0019955 GO:0022414 GO:0030154 GO:0030217 GO:0033210 GO:0038021 GO:0038023 GO:0042593 GO:0043235 GO:0044321 GO:0045721 GO:0046850 GO:0048731 GO:0048856 GO:0051049 GO:0060259 GO:0097009 GO:0097696 GO:0098868 GO:0120162 ILMN_2600710 ILMN_2736578 mMC002415 u42467_s_at
physicalEntity	[EntityWithAccessionedSequence:R-MMU-2586509] p-Y985,Y1077,Y1138-Lepr [plasma membrane] - Mus musculus [EntityWithAccessionedSequence:R-MMU-2586522] Lepr (long isoform) [plasma membrane] - Mus musculus
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12726059] UCSC:P48356 Lepr [ReferenceDNASequence:12031104] NCBI Gene:16847 Lepr [ReferenceDNASequence:11947011] Monarch:16847 Lepr [ReferenceDNASequence:11860447] KEGG:mmu:16847 Lepr [ReferenceDNASequence:11317222] BioGPS Gene:16847 Lepr
referenceTranscript	[ReferenceRNASequence:12505923] RefSeq:NM_146146.4 Lepr [ReferenceRNASequence:12505921] RefSeq:NM_001122899.2 Lepr [ReferenceRNASequence:12505922] RefSeq:NM_010704.3 Lepr
schemaClass	ReferenceIsoform
secondaryIdentifier	LEPR_MOUSE O35686 O54986 Q61215 Q64309 Q9QWG3 Q9QWV5
sequenceLength	1162
species	[Species:48892] Mus musculus
stId	uniprot:P48356-1
url	http://purl.uniprot.org/uniprot/P48356-1
variantIdentifier	P48356-1

Referrals

(interactor)	[UndirectedInteraction:11251631] UniProt:Q8NFJ9 <-> UniProt:P48356-1 (IntAct)
(referenceEntity)	[EntityWithAccessionedSequence:R-MMU-2586509] p-Y985,Y1077,Y1138-Lepr [plasma membrane] [EntityWithAccessionedSequence:R-MMU-2586522] Lepr (long isoform) [plasma membrane]

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