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Protein

Leptin receptor

Gene

Lepr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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:25383904, PubMed:11923481, PubMed:11861497). 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:25383904, PubMed:11923481). 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).1 Publication7 Publications
Isoform A: 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).3 Publications
Isoform E: Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.1 Publication

GO - Molecular functioni

  • identical protein binding Source: MGI
  • leptin receptor activity Source: UniProtKB
  • transmembrane signaling receptor activity Source: MGI

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • bone growth Source: UniProtKB
  • cholesterol metabolic process Source: MGI
  • energy homeostasis Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • leptin-mediated signaling pathway Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of gluconeogenesis Source: MGI
  • negative regulation of hydrolase activity Source: MGI
  • phagocytosis Source: UniProtKB
  • regulation of bone remodeling Source: UniProtKB
  • regulation of energy homeostasis Source: UniProtKB
  • regulation of feeding behavior Source: UniProtKB
  • regulation of metabolic process Source: MGI
  • response to leptin Source: UniProtKB
  • sexual reproduction Source: UniProtKB
  • signal transduction Source: MGI
  • T cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiR-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.

Names & Taxonomyi

Protein namesi
Recommended name:
Leptin receptor
Short name:
LEP-R
Alternative name(s):
B219
OB receptor
Short name:
OB-R
CD_antigen: CD295
Gene namesi
Name:Lepr
Synonyms:Db, Obr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:104993. Lepr.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Basolateral cell membrane By similarity
Isoform E :
  • Secreted 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 839818ExtracellularSequence analysisAdd
BLAST
Transmembranei840 – 86021HelicalSequence analysisAdd
BLAST
Topological domaini861 – 1162302CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

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).5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi891 – 8911E → A: No effect on STAT3 phosphorylation. 1 Publication
Mutagenesisi894 – 8941E → A: No effect on STAT3 phosphorylation. 1 Publication
Mutagenesisi896 – 8972LF → AA: Abrogates STAT3 phosphorylation. 1 Publication
Mutagenesisi899 – 9002KH → AA: No effect on STAT3 phosphorylation. 1 Publication
Mutagenesisi902 – 9021E → A: No effect on STAT3 phosphorylation. 1 Publication
Mutagenesisi908 – 9081P → A: No effect on STAT3 phosphorylation. 1 Publication
Mutagenesisi985 – 9851Y → L: No change in EPO-induced JAK2 activation and EPO-induced tyrosine phosphorylation. No phosphorylation; when associated with S-1138. No phosphorylation; when associated with both S-1138 and F-1077. No change in STAT3 activation. No PTPN11 binding. No SOCS3 binding nor inhibition of signaling. Greatly reduced ERK/FOS activation. Mutants are hyperphagic, obese and hyperglycaemic, females show a defect in lactation. 3 Publications
Mutagenesisi1077 – 10771Y → F: No effect on EPO-induced tyrosine phosphorylation. 1 Publication
Mutagenesisi1138 – 11381Y → S: No change in EPO-induced JAK2 activation and EPO-induced tyrosine phosphorylation. No phosphorylation; when associated with L-985. No phosphorylation; when associated with L-985 and F-1077. No STAT3 activation. No change in SOCS3 binding nor signaling inhibition. No effect on ERK/FOS activation. 2 Publications

Keywords - Diseasei

Obesity

Chemistry

GuidetoPHARMACOLOGYi1712.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 11621141Leptin receptorPRO_0000010906Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi37 ↔ 90By similarity
Glycosylationi41 – 411N-linked (GlcNAc...)Sequence analysis
Glycosylationi56 – 561N-linked (GlcNAc...)Sequence analysis
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence analysis
Disulfide bondi89 ↔ 99By similarity
Glycosylationi98 – 981N-linked (GlcNAc...)Sequence analysis
Disulfide bondi131 ↔ 142By similarity
Disulfide bondi186 ↔ 195By similarity
Glycosylationi187 – 1871N-linked (GlcNAc...)Sequence analysis
Disulfide bondi188 ↔ 193By similarity
Glycosylationi275 – 2751N-linked (GlcNAc...)Sequence analysis
Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence analysis
Disulfide bondi350 ↔ 410By similarity
Disulfide bondi411 ↔ 416By similarity
Glycosylationi431 – 4311N-linked (GlcNAc...)Sequence analysis
Disulfide bondi434 ↔ 445By similarity
Disulfide bondi471 ↔ 526By similarity
Disulfide bondi486 ↔ 496By similarity
Glycosylationi514 – 5141N-linked (GlcNAc...)Sequence analysis
Glycosylationi622 – 6221N-linked (GlcNAc...)Sequence analysis
Glycosylationi657 – 6571N-linked (GlcNAc...)Sequence analysis
Glycosylationi668 – 6681N-linked (GlcNAc...)Sequence analysis
Glycosylationi686 – 6861N-linked (GlcNAc...)Sequence analysis
Glycosylationi695 – 6951N-linked (GlcNAc...)Sequence analysis
Glycosylationi698 – 6981N-linked (GlcNAc...)Sequence analysis
Glycosylationi726 – 7261N-linked (GlcNAc...)Sequence analysis
Modified residuei880 – 8801PhosphoserineCombined sources
Modified residuei985 – 9851Phosphotyrosine; by JAK22 Publications
Modified residuei1077 – 10771Phosphotyrosine1 Publication
Modified residuei1138 – 11381Phosphotyrosine; by JAK21 Publication

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP48356.
PaxDbiP48356.
PeptideAtlasiP48356.
PRIDEiP48356.

PTM databases

iPTMnetiP48356.
PhosphoSiteiP48356.

Expressioni

Tissue specificityi

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).3 Publications

Gene expression databases

BgeeiP48356.
CleanExiMM_LEPR.
ExpressionAtlasiP48356. baseline and differential.
GenevisibleiP48356. MM.

Interactioni

Subunit structurei

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).By similarity1 Publication2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BBS1Q8NFJ93EBI-6143588,EBI-1805484From a different organism.
Plcg1Q620772EBI-2257257,EBI-300133

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201139. 3 interactions.
DIPiDIP-42763N.
IntActiP48356. 10 interactions.
MINTiMINT-2569396.
STRINGi10090.ENSMUSP00000037385.

Structurei

3D structure databases

ProteinModelPortaliP48356.
SMRiP48356. Positions 428-629.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini238 – 33194Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini329 – 42799Ig-likeAdd
BLAST
Domaini537 – 63296Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini637 – 72993Fibronectin type-III 3PROSITE-ProRule annotationAdd
BLAST
Domaini738 – 83295Fibronectin type-III 4PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni465 – 48218Leptin-bindingBy similarityAdd
BLAST
Regioni891 – 8966Required for JAK2 activation1 Publication
Regioni896 – 9049Required for STAT3 phosphorylation1 Publication

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi620 – 6245WSXWS motif
Motifi869 – 8779Box 1 motif

Domaini

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.1 Publication
The box 1 motif is required for JAK interaction and/or activation.1 Publication

Sequence similaritiesi

Contains 4 fibronectin type-III domains.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKH4. Eukaryota.
ENOG4110JZP. LUCA.
GeneTreeiENSGT00730000111209.
HOVERGENiHBG000140.
InParanoidiP48356.
KOiK05062.
OMAiGLLKISW.
OrthoDBiEOG7034GB.
PhylomeDBiP48356.
TreeFamiTF106501.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR003531. Hempt_rcpt_S_F1_CS.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
IPR015752. Lep_receptor.
[Graphical view]
PANTHERiPTHR23036:SF109. PTHR23036:SF109. 3 hits.
PfamiPF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 4 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 3 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B (identifier: P48356-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MMCQKFYVVL LHWEFLYVIA ALNLAYPISP WKFKLFCGPP NTTDDSFLSP
60 70 80 90 100
AGAPNNASAL KGASEAIVEA KFNSSGIYVP ELSKTVFHCC FGNEQGQNCS
110 120 130 140 150
ALTDNTEGKT LASVVKASVF RQLGVNWDIE CWMKGDLTLF ICHMEPLPKN
160 170 180 190 200
PFKNYDSKVH LLYDLPEVID DSPLPPLKDS FQTVQCNCSL RGCECHVPVP
210 220 230 240 250
RAKLNYALLM YLEITSAGVS FQSPLMSLQP MLVVKPDPPL GLHMEVTDDG
260 270 280 290 300
NLKISWDSQT MAPFPLQYQV KYLENSTIVR EAAEIVSATS LLVDSVLPGS
310 320 330 340 350
SYEVQVRSKR LDGSGVWSDW SSPQVFTTQD VVYFPPKILT SVGSNASFHC
360 370 380 390 400
IYKNENQIIS SKQIVWWRNL AEKIPEIQYS IVSDRVSKVT FSNLKATRPR
410 420 430 440 450
GKFTYDAVYC CNEQACHHRY AELYVIDVNI NISCETDGYL TKMTCRWSPS
460 470 480 490 500
TIQSLVGSTV QLRYHRRSLY CPDSPSIHPT SEPKNCVLQR DGFYECVFQP
510 520 530 540 550
IFLLSGYTMW IRINHSLGSL DSPPTCVLPD SVVKPLPPSN VKAEITVNTG
560 570 580 590 600
LLKVSWEKPV FPENNLQFQI RYGLSGKEIQ WKTHEVFDAK SKSASLLVSD
610 620 630 640 650
LCAVYVVQVR CRRLDGLGYW SNWSSPAYTL VMDVKVPMRG PEFWRKMDGD
660 670 680 690 700
VTKKERNVTL LWKPLTKNDS LCSVRRYVVK HRTAHNGTWS EDVGNRTNLT
710 720 730 740 750
FLWTEPAHTV TVLAVNSLGA SLVNFNLTFS WPMSKVSAVE SLSAYPLSSS
760 770 780 790 800
CVILSWTLSP DDYSLLYLVI EWKILNEDDG MKWLRIPSNV KKFYIHDNFI
810 820 830 840 850
PIEKYQFSLY PVFMEGVGKP KIINGFTKDA IDKQQNDAGL YVIVPIIISS
860 870 880 890 900
CVLLLGTLLI SHQRMKKLFW DDVPNPKNCS WAQGLNFQKP ETFEHLFTKH
910 920 930 940 950
AESVIFGPLL LEPEPISEEI SVDTAWKNKD EMVPAAMVSL LLTTPDPESS
960 970 980 990 1000
SICISDQCNS ANFSGSQSTQ VTCEDECQRQ PSVKYATLVS NDKLVETDEE
1010 1020 1030 1040 1050
QGFIHSPVSN CISSNHSPLR QSFSSSSWET EAQTFFLLSD QQPTMISPQL
1060 1070 1080 1090 1100
SFSGLDELLE LEGSFPEENH REKSVCYLGV TSVNRRESGV LLTGEAGILC
1110 1120 1130 1140 1150
TFPAQCLFSD IRILQERCSH FVENNLSLGT SGENFVPYMP QFQTCSTHSH
1160
KIMENKMCDL TV
Length:1,162
Mass (Da):130,789
Last modified:February 1, 1996 - v1
Checksum:i0E1E75B076BA60A2
GO
Isoform A (identifier: P48356-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     890-894: PETFE → RTDTL
     895-1162: Missing.

Show »
Length:894
Mass (Da):101,058
Checksum:iDF9A7A0E5AC75A53
GO
Isoform C (identifier: P48356-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     890-892: PET → VTV
     893-1162: Missing.

Show »
Length:892
Mass (Da):100,771
Checksum:i726E5C075A53C9F3
GO
Isoform D (identifier: P48356-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     890-900: PETFEHLFTKH → DISFHEVFIFR
     901-1162: Missing.

Show »
Length:900
Mass (Da):101,863
Checksum:i7370A3C7BB5E7942
GO
Isoform E (identifier: P48356-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     797-805: DNFIPIEKY → GMCTVLFMD
     806-1162: Missing.

Show »
Length:805
Mass (Da):90,887
Checksum:i591B5DE008BDB898
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti140 – 1401F → I in AAC52705 (PubMed:8692797).Curated
Sequence conflicti140 – 1401F → I in AAC52706 (PubMed:8692797).Curated
Sequence conflicti140 – 1401F → I in AAC52707 (PubMed:8692797).Curated
Sequence conflicti720 – 7201A → T in CAA71343 (PubMed:9322935).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti541 – 5411V → I in strain: NZO.
Natural varianti600 – 6001D → N in strain: KK Obese. 1 Publication
Natural varianti651 – 6511V → I in strain: NZO.
Natural varianti1044 – 10441T → I in strain: NZO.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei797 – 8059DNFIPIEKY → GMCTVLFMD in isoform E. 1 PublicationVSP_001703
Alternative sequencei806 – 1162357Missing in isoform E. 1 PublicationVSP_001704Add
BLAST
Alternative sequencei890 – 90011PETFEHLFTKH → DISFHEVFIFR in isoform D. 1 PublicationVSP_001701Add
BLAST
Alternative sequencei890 – 8945PETFE → RTDTL in isoform A. 3 PublicationsVSP_001697
Alternative sequencei890 – 8923PET → VTV in isoform C. 2 PublicationsVSP_001699
Alternative sequencei893 – 1162270Missing in isoform C. 2 PublicationsVSP_001700Add
BLAST
Alternative sequencei895 – 1162268Missing in isoform A. 3 PublicationsVSP_001698Add
BLAST
Alternative sequencei901 – 1162262Missing in isoform D. 1 PublicationVSP_001702Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U42467 mRNA. Translation: AAA93014.1.
U46135 mRNA. Translation: AAC52408.1.
U49106 mRNA. Translation: AAC52420.1.
U49107 mRNA. Translation: AAC52421.1.
U49108 mRNA. Translation: AAC52422.1.
U49109 mRNA. Translation: AAC52423.1.
U49110 mRNA. Translation: AAC52424.1.
U52915 mRNA. Translation: AAC52599.1.
U58861 mRNA. Translation: AAC52705.1.
U58862 mRNA. Translation: AAC52706.1.
U58863 mRNA. Translation: AAC52707.1.
Y10298 mRNA. Translation: CAA71343.1.
AF039456
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455 Genomic DNA. Translation: AAB95334.1.
AF039461
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458, AF039459 Genomic DNA. Translation: AAB95333.1. Different termination.
AF039459
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458 Genomic DNA. Translation: AAB95335.1.
AF039460
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458, AF039459 Genomic DNA. Translation: AAB95332.1.
Y10296 mRNA. Translation: CAA71342.1.
AF098792 Genomic DNA. Translation: AAD13218.1.
CCDSiCCDS18397.1. [P48356-3]
CCDS51239.1. [P48356-2]
CCDS51240.1. [P48356-1]
PIRiS68437.
S68438.
S68439.
S68440.
S68441.
RefSeqiNP_001116371.1. NM_001122899.1. [P48356-2]
NP_034834.1. NM_010704.2. [P48356-3]
NP_666258.2. NM_146146.2. [P48356-1]
UniGeneiMm.259282.

Genome annotation databases

EnsembliENSMUST00000037552; ENSMUSP00000037385; ENSMUSG00000057722. [P48356-1]
ENSMUST00000102777; ENSMUSP00000099838; ENSMUSG00000057722. [P48356-3]
ENSMUST00000106921; ENSMUSP00000102534; ENSMUSG00000057722. [P48356-2]
GeneIDi16847.
KEGGimmu:16847.
UCSCiuc008tvx.2. mouse. [P48356-1]
uc008twa.1. mouse. [P48356-5]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U42467 mRNA. Translation: AAA93014.1.
U46135 mRNA. Translation: AAC52408.1.
U49106 mRNA. Translation: AAC52420.1.
U49107 mRNA. Translation: AAC52421.1.
U49108 mRNA. Translation: AAC52422.1.
U49109 mRNA. Translation: AAC52423.1.
U49110 mRNA. Translation: AAC52424.1.
U52915 mRNA. Translation: AAC52599.1.
U58861 mRNA. Translation: AAC52705.1.
U58862 mRNA. Translation: AAC52706.1.
U58863 mRNA. Translation: AAC52707.1.
Y10298 mRNA. Translation: CAA71343.1.
AF039456
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455 Genomic DNA. Translation: AAB95334.1.
AF039461
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458, AF039459 Genomic DNA. Translation: AAB95333.1. Different termination.
AF039459
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458 Genomic DNA. Translation: AAB95335.1.
AF039460
, AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458, AF039459 Genomic DNA. Translation: AAB95332.1.
Y10296 mRNA. Translation: CAA71342.1.
AF098792 Genomic DNA. Translation: AAD13218.1.
CCDSiCCDS18397.1. [P48356-3]
CCDS51239.1. [P48356-2]
CCDS51240.1. [P48356-1]
PIRiS68437.
S68438.
S68439.
S68440.
S68441.
RefSeqiNP_001116371.1. NM_001122899.1. [P48356-2]
NP_034834.1. NM_010704.2. [P48356-3]
NP_666258.2. NM_146146.2. [P48356-1]
UniGeneiMm.259282.

3D structure databases

ProteinModelPortaliP48356.
SMRiP48356. Positions 428-629.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201139. 3 interactions.
DIPiDIP-42763N.
IntActiP48356. 10 interactions.
MINTiMINT-2569396.
STRINGi10090.ENSMUSP00000037385.

Chemistry

GuidetoPHARMACOLOGYi1712.

PTM databases

iPTMnetiP48356.
PhosphoSiteiP48356.

Proteomic databases

MaxQBiP48356.
PaxDbiP48356.
PeptideAtlasiP48356.
PRIDEiP48356.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037552; ENSMUSP00000037385; ENSMUSG00000057722. [P48356-1]
ENSMUST00000102777; ENSMUSP00000099838; ENSMUSG00000057722. [P48356-3]
ENSMUST00000106921; ENSMUSP00000102534; ENSMUSG00000057722. [P48356-2]
GeneIDi16847.
KEGGimmu:16847.
UCSCiuc008tvx.2. mouse. [P48356-1]
uc008twa.1. mouse. [P48356-5]

Organism-specific databases

CTDi3953.
MGIiMGI:104993. Lepr.

Phylogenomic databases

eggNOGiENOG410IKH4. Eukaryota.
ENOG4110JZP. LUCA.
GeneTreeiENSGT00730000111209.
HOVERGENiHBG000140.
InParanoidiP48356.
KOiK05062.
OMAiGLLKISW.
OrthoDBiEOG7034GB.
PhylomeDBiP48356.
TreeFamiTF106501.

Enzyme and pathway databases

ReactomeiR-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.

Miscellaneous databases

PROiP48356.
SOURCEiSearch...

Gene expression databases

BgeeiP48356.
CleanExiMM_LEPR.
ExpressionAtlasiP48356. baseline and differential.
GenevisibleiP48356. MM.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR003531. Hempt_rcpt_S_F1_CS.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
IPR015752. Lep_receptor.
[Graphical view]
PANTHERiPTHR23036:SF109. PTHR23036:SF109. 3 hits.
PfamiPF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 4 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 3 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
    Tissue: Choroid plexus.
  2. "Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice."
    Chen H., Charlat O., Tartaglia L.A., Woolf E.A., Weng X., Ellis S.J., Lakey N.D., Culpepper J., Moore K.J., Breitbart R.E., Duyk G.M., Tepper R.I., Morgenstern J.P.
    Cell 84:491-495(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
    Strain: C57BLKS/J.
    Tissue: Hypothalamus.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C; D AND E).
    Strain: C57BLKS/J.
    Tissue: Hypothalamus.
  4. "Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction."
    Cioffi J.A., Shafer A.W., Zupancic T.J., Smith-Gbur J., Mikhail A., Platika D., Snodgrass H.R.
    Nat. Med. 2:585-589(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
    Strain: BALB/cJ.
    Tissue: Liver.
  5. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
    Strain: FVB/N.
    Tissue: Spleen.
  6. "Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse."
    Igel M., Becker W., Herberg L., Joost H.G.
    Endocrinology 138:4234-4239(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
    Strain: NZO.
    Tissue: Hypothalamus.
  7. "Fine structure of the murine leptin receptor gene: splice site suppression is required to form two alternatively spliced transcripts."
    Chua S.C., Koutras I.K., Han L., Liu S.M., Kay J., Young S.J., Chung W.K., Leibel R.L.
    Genomics 45:264-270(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; B; C AND E).
    Strain: 129/J.
  8. "Hyperleptinemia and leptin receptor variant Asp600Asn in the obese, hyperinsulinemic KK mouse strain."
    Igel M., Taylor B.A., Phillips S.J., Becker W., Herberg L., Joost H.G.
    J. Endocrinol. 21:337-345(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT ASN-600.
    Strain: KK Obese.
    Tissue: Hypothalamus.
  9. "Murine leptin receptor genomic exon 18b and surrounding sequence."
    Banks A.S., Myers M.G. Jr.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE OF 890-1162 (ISOFORM B).
    Strain: 129.
  10. "Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression."
    Lord G.M., Matarese G., Howard J.K., Baker R.J., Bloom S.R., Lechler R.I.
    Nature 394:897-901(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
  11. "Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass."
    Ducy P., Amling M., Takeda S., Priemel M., Schilling A.F., Beil F.T., Shen J., Vinson C., Rueger J.M., Karsenty G.
    Cell 100:197-207(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  12. "Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in the murine leptin receptor."
    Eyckerman S., Broekaert D., Verhee A., Vandekerckhove J., Tavernier J.
    FEBS Lett. 486:33-37(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-985 AND TYR-1077.
  13. "Activation of downstream signals by the long form of the leptin receptor."
    Banks A.S., Davis S.M., Bates S.H., Myers M.G. Jr.
    J. Biol. Chem. 275:14563-14572(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-985 AND TYR-1138, STAT3 ACTIVATION, ERK/FOS ACTIVATION, MUTAGENESIS OF TYR-985; TYR-1077 AND TYR-1138.
  14. "SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985."
    Bjorbaek C., Lavery H.J., Bates S.H., Olson R.K., Davis S.M., Flier J.S., Myers M.G. Jr.
    J. Biol. Chem. 275:40649-40657(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SOCS3, MUTAGENESIS OF TYR-985 AND TYR-1138.
  15. "Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity."
    Hileman S.M., Pierroz D.D., Masuzaki H., Bjoerbaek C., El-Haschimi K., Banks W.A., Flier J.S.
    Endocrinology 143:775-783(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  16. "Regulation of Jak kinases by intracellular leptin receptor sequences."
    Kloek C., Haq A.K., Dunn S.L., Lavery H.J., Banks A.S., Myers M.G. Jr.
    J. Biol. Chem. 277:41547-41555(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN JAK2 ACTIVATION.
  17. "Identification of the critical sequence elements in the cytoplasmic domain of leptin receptor isoforms required for Janus kinase/signal transducer and activator of transcription activation by receptor heterodimers."
    Bahrenberg G., Behrmann I., Barthel A., Hekerman P., Heinrich P.C., Joost H.G., Becker W.
    Mol. Endocrinol. 16:859-872(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM A AND ISOFORM B), INTERACTION WITH JAK2, MUTAGENESIS OF GLU-891; GLU-894; 896-LEU-PHE-897; 899-LYS-HIS-900; GLU-902 AND PRO-908.
  18. Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF TYR-1138.
  19. Cited for: FUNCTION (ISOFORM A AND ISOFORM E), TISSUE SPECIFICITY (ISOFORM E), SUBCELLULAR LOCATION (ISOFORM E).
  20. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-880, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney.
  21. "Unique leptin trafficking by a tailless receptor."
    Tu H., Hsuchou H., Kastin A.J., Wu X., Pan W.
    FASEB J. 24:2281-2291(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM A).
  22. "20 years of leptin: connecting leptin signaling to biological function."
    Allison M.B., Myers M.G. Jr.
    J. Endocrinol. 223:T25-T35(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION, SUBUNIT.
  23. Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiLEPR_MOUSE
AccessioniPrimary (citable) accession number: P48356
Secondary accession number(s): O35686
, O54986, Q61215, Q64309, Q9QWG3, Q9QWV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 6, 2016
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.