LEPR_MOUSE
ID LEPR_MOUSE Reviewed; 1162 AA.
AC P48356; O35686; O54986; Q61215; Q64309; Q9QWG3; Q9QWV5;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Leptin receptor;
DE Short=LEP-R;
DE AltName: Full=B219;
DE AltName: Full=OB receptor;
DE Short=OB-R;
DE AltName: CD_antigen=CD295;
DE Flags: Precursor;
GN Name=Lepr; Synonyms=Db, Obr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Choroid plexus;
RX PubMed=8548812; DOI=10.1016/0092-8674(95)90151-5;
RA Tartaglia L.A., Dembski M., Weng X., Deng N., Culpepper J., Devos R.,
RA Richards G.J., Campfield L.A., Clark F.T., Deeds J., Muir C., Sanker S.,
RA Moriarty A., Moore K.J., Smutko J.S., Mays G.G., Woolf E.A., Monroe C.A.,
RA Tepper R.I.;
RT "Identification and expression cloning of a leptin receptor, OB-R.";
RL Cell 83:1263-1271(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC STRAIN=C57BLKS/J; TISSUE=Hypothalamus;
RX PubMed=8608603; DOI=10.1016/s0092-8674(00)81294-5;
RA Chen H., Charlat O., Tartaglia L.A., Woolf E.A., Weng X., Ellis S.J.,
RA Lakey N.D., Culpepper J., Moore K.J., Breitbart R.E., Duyk G.M.,
RA Tepper R.I., Morgenstern J.P.;
RT "Evidence that the diabetes gene encodes the leptin receptor:
RT identification of a mutation in the leptin receptor gene in db/db mice.";
RL Cell 84:491-495(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C; D AND E).
RC STRAIN=C57BLKS/J; TISSUE=Hypothalamus;
RX PubMed=8628397; DOI=10.1038/379632a0;
RA Lee G.-H., Proenca R., Montez J.M., Carroll K.M., Darvishzadeh J.G.,
RA Lee J.I., Friedman J.M.;
RT "Abnormal splicing of the leptin receptor in diabetic mice.";
RL Nature 379:632-635(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=8616721; DOI=10.1038/nm0596-585;
RA Cioffi J.A., Shafer A.W., Zupancic T.J., Smith-Gbur J., Mikhail A.,
RA Platika D., Snodgrass H.R.;
RT "Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis
RT and reproduction.";
RL Nat. Med. 2:585-589(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RC STRAIN=FVB/N; TISSUE=Spleen;
RX PubMed=8692797; DOI=10.1073/pnas.93.13.6231;
RA Ghilardi N., Ziegler S., Wiestner A., Stoffel R., Heim M.H., Skoda R.C.;
RT "Defective STAT signaling by the leptin receptor in diabetic mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6231-6235(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC STRAIN=NZO; TISSUE=Hypothalamus;
RX PubMed=9322935; DOI=10.1210/endo.138.10.5428;
RA Igel M., Becker W., Herberg L., Joost H.G.;
RT "Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the
RT New Zealand obese mouse.";
RL Endocrinology 138:4234-4239(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; B; C AND E).
RC STRAIN=129/J;
RX PubMed=9344648; DOI=10.1006/geno.1997.4962;
RA Chua S.C., Koutras I.K., Han L., Liu S.M., Kay J., Young S.J., Chung W.K.,
RA Leibel R.L.;
RT "Fine structure of the murine leptin receptor gene: splice site suppression
RT is required to form two alternatively spliced transcripts.";
RL Genomics 45:264-270(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND VARIANT ASN-600.
RC STRAIN=KK Obese; TISSUE=Hypothalamus;
RX PubMed=9845674; DOI=10.1677/jme.0.0210337;
RA Igel M., Taylor B.A., Phillips S.J., Becker W., Herberg L., Joost H.G.;
RT "Hyperleptinemia and leptin receptor variant Asp600Asn in the obese,
RT hyperinsulinemic KK mouse strain.";
RL J. Endocrinol. 21:337-345(1998).
RN [9]
RP NUCLEOTIDE SEQUENCE OF 890-1162 (ISOFORM B).
RC STRAIN=129;
RA Banks A.S., Myers M.G. Jr.;
RT "Murine leptin receptor genomic exon 18b and surrounding sequence.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=9732873; DOI=10.1038/29795;
RA Lord G.M., Matarese G., Howard J.K., Baker R.J., Bloom S.R., Lechler R.I.;
RT "Leptin modulates the T-cell immune response and reverses starvation-
RT induced immunosuppression.";
RL Nature 394:897-901(1998).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10660043; DOI=10.1016/s0092-8674(00)81558-5;
RA Ducy P., Amling M., Takeda S., Priemel M., Schilling A.F., Beil F.T.,
RA Shen J., Vinson C., Rueger J.M., Karsenty G.;
RT "Leptin inhibits bone formation through a hypothalamic relay: a central
RT control of bone mass.";
RL Cell 100:197-207(2000).
RN [12]
RP PHOSPHORYLATION AT TYR-985 AND TYR-1077.
RX PubMed=11108838; DOI=10.1016/s0014-5793(00)02205-5;
RA Eyckerman S., Broekaert D., Verhee A., Vandekerckhove J., Tavernier J.;
RT "Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in
RT the murine leptin receptor.";
RL FEBS Lett. 486:33-37(2000).
RN [13]
RP PHOSPHORYLATION AT TYR-985 AND TYR-1138, STAT3 ACTIVATION, ERK/FOS
RP ACTIVATION, AND MUTAGENESIS OF TYR-985; TYR-1077 AND TYR-1138.
RX PubMed=10799542; DOI=10.1074/jbc.275.19.14563;
RA Banks A.S., Davis S.M., Bates S.H., Myers M.G. Jr.;
RT "Activation of downstream signals by the long form of the leptin
RT receptor.";
RL J. Biol. Chem. 275:14563-14572(2000).
RN [14]
RP INTERACTION WITH SOCS3, AND MUTAGENESIS OF TYR-985 AND TYR-1138.
RX PubMed=11018044; DOI=10.1074/jbc.m007577200;
RA Bjorbaek C., Lavery H.J., Bates S.H., Olson R.K., Davis S.M., Flier J.S.,
RA Myers M.G. Jr.;
RT "SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985.";
RL J. Biol. Chem. 275:40649-40657(2000).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11861497; DOI=10.1210/endo.143.3.8669;
RA Hileman S.M., Pierroz D.D., Masuzaki H., Bjoerbaek C., El-Haschimi K.,
RA Banks W.A., Flier J.S.;
RT "Characterization of short isoforms of the leptin receptor in rat cerebral
RT microvessels and of brain uptake of leptin in mouse models of obesity.";
RL Endocrinology 143:775-783(2002).
RN [16]
RP DOMAIN JAK2 ACTIVATION.
RX PubMed=12196522; DOI=10.1074/jbc.m205148200;
RA Kloek C., Haq A.K., Dunn S.L., Lavery H.J., Banks A.S., Myers M.G. Jr.;
RT "Regulation of Jak kinases by intracellular leptin receptor sequences.";
RL J. Biol. Chem. 277:41547-41555(2002).
RN [17]
RP FUNCTION (ISOFORM A AND ISOFORM B), INTERACTION WITH JAK2, AND MUTAGENESIS
RP OF GLU-891; GLU-894; 896-LEU-PHE-897; 899-LYS-HIS-900; GLU-902 AND PRO-908.
RX PubMed=11923481; DOI=10.1210/mend.16.4.0800;
RA Bahrenberg G., Behrmann I., Barthel A., Hekerman P., Heinrich P.C.,
RA Joost H.G., Becker W.;
RT "Identification of the critical sequence elements in the cytoplasmic domain
RT of leptin receptor isoforms required for Janus kinase/signal transducer and
RT activator of transcription activation by receptor heterodimers.";
RL Mol. Endocrinol. 16:859-872(2002).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-1138.
RX PubMed=12594516; DOI=10.1038/nature01388;
RA Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y.,
RA Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G.,
RA Schwartz M.W., Myers M.G. Jr.;
RT "STAT3 signalling is required for leptin regulation of energy balance but
RT not reproduction.";
RL Nature 421:856-859(2003).
RN [19]
RP FUNCTION (ISOFORM A AND ISOFORM E), TISSUE SPECIFICITY (ISOFORM E), AND
RP SUBCELLULAR LOCATION (ISOFORM E).
RX PubMed=17620316; DOI=10.1002/jcp.21195;
RA Tu H., Kastin A.J., Hsuchou H., Pan W.;
RT "Soluble receptor inhibits leptin transport.";
RL J. Cell. Physiol. 214:301-305(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-880, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [21]
RP FUNCTION (ISOFORM A).
RX PubMed=20223942; DOI=10.1096/fj.09-143487;
RA Tu H., Hsuchou H., Kastin A.J., Wu X., Pan W.;
RT "Unique leptin trafficking by a tailless receptor.";
RL FASEB J. 24:2281-2291(2010).
RN [22]
RP REVIEW ON FUNCTION, AND SUBUNIT.
RX PubMed=25232147; DOI=10.1530/joe-14-0404;
RA Allison M.B., Myers M.G. Jr.;
RT "20 years of leptin: connecting leptin signaling to biological function.";
RL J. Endocrinol. 223:T25-T35(2014).
RN [23]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=25383904; DOI=10.1038/nn.3861;
RA Flak J.N., Patterson C.M., Garfield A.S., D'Agostino G., Goforth P.B.,
RA Sutton A.K., Malec P.A., Wong J.M., Germani M., Jones J.C., Rajala M.,
RA Satin L., Rhodes C.J., Olson D.P., Kennedy R.T., Heisler L.K.,
RA Myers M.G. Jr.;
RT "Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative
RT energy balance.";
RL Nat. Neurosci. 17:1744-1750(2014).
CC -!- FUNCTION: Receptor for hormone LEP/leptin (Probable) (PubMed:11861497).
CC On ligand binding, mediates LEP central and peripheral effects through
CC the activation of different signaling pathways such as JAK2/STAT3 and
CC MAPK cascade/FOS (PubMed:10799542, PubMed:25383904, PubMed:11923481,
CC PubMed:11861497). In the hypothalamus, LEP acts as an appetite-
CC regulating factor that induces a decrease in food intake and an
CC increase in energy consumption by inducing anorexinogenic factors and
CC suppressing orexigenic neuropeptides, also regulates bone mass and
CC secretion of hypothalamo-pituitary-adrenal hormones (PubMed:10660043,
CC PubMed:12594516). In the periphery, increases basal metabolism,
CC influences reproductive function, regulates pancreatic beta-cell
CC function and insulin secretion, is pro-angiogenic and affects innate
CC and adaptive immunity (PubMed:25383904, PubMed:11923481). Control of
CC energy homeostasis and melanocortin production (stimulation of POMC and
CC full repression of AgRP transcription) is mediated by STAT3 signaling,
CC whereas distinct signals regulate NPY and the control of fertility,
CC growth and glucose homeostasis (PubMed:12594516). Involved in the
CC regulation of counter-regulatory response to hypoglycemia by inhibiting
CC neurons of the parabrachial nucleus (PubMed:25383904). Has a specific
CC effect on T lymphocyte responses, differentially regulating the
CC proliferation of naive and memory T-cells. Leptin increases Th1 and
CC suppresses Th2 cytokine production (PubMed:9732873).
CC {ECO:0000269|PubMed:10660043, ECO:0000269|PubMed:10799542,
CC ECO:0000269|PubMed:11861497, ECO:0000269|PubMed:11923481,
CC ECO:0000269|PubMed:12594516, ECO:0000269|PubMed:25383904,
CC ECO:0000269|PubMed:9732873, ECO:0000305|PubMed:25232147}.
CC -!- FUNCTION: [Isoform A]: May transport LEP across the blood-brain
CC barrier. Binds LEP and mediates LEP endocytosis (PubMed:17620316,
CC PubMed:20223942). Does not induce phosphorylation of and activate STAT3
CC (PubMed:11923481, PubMed:20223942). {ECO:0000269|PubMed:11923481,
CC ECO:0000269|PubMed:17620316, ECO:0000269|PubMed:20223942}.
CC -!- FUNCTION: [Isoform E]: Antagonizes Isoform A and isoform B-mediated LEP
CC binding and endocytosis. {ECO:0000269|PubMed:17620316}.
CC -!- SUBUNIT: Present as a mixture of monomers and dimers (Probable). The
CC phosphorylated receptor binds a number of SH2 domain-containing
CC proteins such as JAK2, STAT3, PTPN11, and SOCS3 (By similarity)
CC (PubMed:11018044, PubMed:11923481). Interaction with SOCS3 inhibits
CC JAK/STAT signaling and MAPK cascade (PubMed:11018044).
CC {ECO:0000250|UniProtKB:P48357, ECO:0000269|PubMed:11018044,
CC ECO:0000269|PubMed:11923481, ECO:0000305|PubMed:25232147}.
CC -!- INTERACTION:
CC P48356; Q62120: Jak2; NbExp=3; IntAct=EBI-2257257, EBI-646604;
CC P48356; P41160: Lep; NbExp=6; IntAct=EBI-2257257, EBI-16108810;
CC P48356; Q91ZX7: Lrp1; NbExp=2; IntAct=EBI-2257257, EBI-300955;
CC P48356; Q62077: Plcg1; NbExp=2; IntAct=EBI-2257257, EBI-300133;
CC P48356-1; Q8NFJ9: BBS1; Xeno; NbExp=3; IntAct=EBI-6143588, EBI-1805484;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P48357};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P48357}.
CC Basolateral cell membrane {ECO:0000250|UniProtKB:P48357}.
CC -!- SUBCELLULAR LOCATION: [Isoform E]: Secreted
CC {ECO:0000305|PubMed:17620316}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=B;
CC IsoId=P48356-1; Sequence=Displayed;
CC Name=A;
CC IsoId=P48356-2; Sequence=VSP_001697, VSP_001698;
CC Name=C;
CC IsoId=P48356-3; Sequence=VSP_001699, VSP_001700;
CC Name=D;
CC IsoId=P48356-4; Sequence=VSP_001701, VSP_001702;
CC Name=E;
CC IsoId=P48356-5; Sequence=VSP_001703, VSP_001704;
CC -!- TISSUE SPECIFICITY: Isoform A: highest level of expression in lung and
CC kidney, also present in heart, brain, spleen, liver, muscle, choroid
CC plexus and hypothalamus. Isoform B: highest levels of expression in
CC hypothalamus and lower levels in brain, testes and adipose tissue.
CC Expressed by neurons of the parabrachial nucleus (PubMed:25383904).
CC Expressed by peripheral blood mononuclear cells and CD4(+) T-cells
CC (PubMed:9732873). Isoform E: expressed in adipose tissue, liver,
CC hypothalamus, cerebral microvessels, heart, and testes
CC (PubMed:17620316). {ECO:0000269|PubMed:17620316,
CC ECO:0000269|PubMed:25383904, ECO:0000269|PubMed:9732873}.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding. {ECO:0000269|PubMed:12196522}.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation. {ECO:0000269|PubMed:12196522}.
CC -!- PTM: On ligand binding, phosphorylated on two conserved C-terminal
CC tyrosine residues (isoform B only) by JAK2. Tyr-985 is required for
CC complete binding and activation of PTPN11, ERK/FOS activation,for
CC interaction with SOCS3 and SOCS3 mediated inhibition of leptin
CC signaling. Phosphorylation on Tyr-1138 is required for STAT3
CC binding/activation. Phosphorylation of Tyr-1077 has a more accessory
CC role. {ECO:0000269|PubMed:10799542, ECO:0000269|PubMed:11108838}.
CC -!- DISRUPTION PHENOTYPE: Mutants are hyperphagic, obese, infertile,
CC diabetic and have impaired growth (PubMed:12594516). Have wet brain
CC weight significantly lower than controls. Brain uptake of leptin is
CC also reduced (PubMed:11861497). Animals have an increased bone
CC formation leading to high bone mass (PubMed:10660043). Have impaired T-
CC cell immunity, Th2 responses are favoured in mutants (PubMed:9732873).
CC Conditional knockout in parabrachial nucleus CCK-expressing neurons,
CC treated with 2-deoxyglucose, have increased levels of glucagon,
CC corticosterone and epinephrin concentrations compared to wild-types
CC (PubMed:25383904). {ECO:0000269|PubMed:10660043,
CC ECO:0000269|PubMed:11861497, ECO:0000269|PubMed:12594516,
CC ECO:0000269|PubMed:25383904, ECO:0000269|PubMed:9732873}.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; U42467; AAA93014.1; -; mRNA.
DR EMBL; U46135; AAC52408.1; -; mRNA.
DR EMBL; U49106; AAC52420.1; -; mRNA.
DR EMBL; U49107; AAC52421.1; -; mRNA.
DR EMBL; U49108; AAC52422.1; -; mRNA.
DR EMBL; U49109; AAC52423.1; -; mRNA.
DR EMBL; U49110; AAC52424.1; -; mRNA.
DR EMBL; U52915; AAC52599.1; -; mRNA.
DR EMBL; U58861; AAC52705.1; -; mRNA.
DR EMBL; U58862; AAC52706.1; -; mRNA.
DR EMBL; U58863; AAC52707.1; -; mRNA.
DR EMBL; Y10298; CAA71343.1; -; mRNA.
DR EMBL; AF039456; AAB95334.1; -; Genomic_DNA.
DR EMBL; AF039443; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039444; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039445; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039446; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039447; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039448; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039449; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039450; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039451; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039452; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039453; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039454; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039455; AAB95334.1; JOINED; Genomic_DNA.
DR EMBL; AF039461; AAB95333.1; ALT_TERM; Genomic_DNA.
DR EMBL; AF039443; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039444; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039445; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039446; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039447; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039448; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039449; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039450; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039451; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039452; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039453; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039454; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039455; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039456; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039457; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039458; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039459; AAB95333.1; JOINED; Genomic_DNA.
DR EMBL; AF039459; AAB95335.1; -; Genomic_DNA.
DR EMBL; AF039443; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039444; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039445; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039446; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039447; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039448; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039449; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039450; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039451; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039452; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039453; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039454; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039455; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039456; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039457; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039458; AAB95335.1; JOINED; Genomic_DNA.
DR EMBL; AF039460; AAB95332.1; -; Genomic_DNA.
DR EMBL; AF039443; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039444; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039445; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039446; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039447; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039448; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039449; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039450; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039451; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039452; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039453; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039454; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039455; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039456; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039457; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039458; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; AF039459; AAB95332.1; JOINED; Genomic_DNA.
DR EMBL; Y10296; CAA71342.1; -; mRNA.
DR EMBL; AF098792; AAD13218.1; -; Genomic_DNA.
DR CCDS; CCDS18397.1; -. [P48356-3]
DR CCDS; CCDS51239.1; -. [P48356-2]
DR CCDS; CCDS51240.1; -. [P48356-1]
DR PIR; S68437; S68437.
DR PIR; S68438; S68438.
DR PIR; S68439; S68439.
DR PIR; S68440; S68440.
DR PIR; S68441; S68441.
DR RefSeq; NP_001116371.1; NM_001122899.1. [P48356-2]
DR RefSeq; NP_034834.1; NM_010704.2. [P48356-3]
DR RefSeq; NP_666258.2; NM_146146.2. [P48356-1]
DR AlphaFoldDB; P48356; -.
DR BioGRID; 201139; 9.
DR CORUM; P48356; -.
DR DIP; DIP-42763N; -.
DR ELM; P48356; -.
DR IntAct; P48356; 13.
DR MINT; P48356; -.
DR STRING; 10090.ENSMUSP00000037385; -.
DR GuidetoPHARMACOLOGY; 1712; -.
DR GlyGen; P48356; 16 sites.
DR iPTMnet; P48356; -.
DR PhosphoSitePlus; P48356; -.
DR CPTAC; non-CPTAC-4044; -.
DR MaxQB; P48356; -.
DR PaxDb; P48356; -.
DR PeptideAtlas; P48356; -.
DR PRIDE; P48356; -.
DR ProteomicsDB; 264736; -. [P48356-1]
DR ProteomicsDB; 264737; -. [P48356-2]
DR ProteomicsDB; 264738; -. [P48356-3]
DR ProteomicsDB; 264739; -. [P48356-4]
DR ProteomicsDB; 264740; -. [P48356-5]
DR Antibodypedia; 33374; 903 antibodies from 44 providers.
DR DNASU; 16847; -.
DR Ensembl; ENSMUST00000037552; ENSMUSP00000037385; ENSMUSG00000057722. [P48356-1]
DR Ensembl; ENSMUST00000102777; ENSMUSP00000099838; ENSMUSG00000057722. [P48356-3]
DR Ensembl; ENSMUST00000106921; ENSMUSP00000102534; ENSMUSG00000057722. [P48356-2]
DR GeneID; 16847; -.
DR KEGG; mmu:16847; -.
DR UCSC; uc008tvx.2; mouse. [P48356-1]
DR UCSC; uc008twa.1; mouse. [P48356-5]
DR CTD; 3953; -.
DR MGI; MGI:104993; Lepr.
DR VEuPathDB; HostDB:ENSMUSG00000057722; -.
DR eggNOG; ENOG502RK5B; Eukaryota.
DR GeneTree; ENSGT00730000111209; -.
DR HOGENOM; CLU_008491_0_0_1; -.
DR InParanoid; P48356; -.
DR OMA; FPPHCLF; -.
DR OrthoDB; 144839at2759; -.
DR PhylomeDB; P48356; -.
DR TreeFam; TF106501; -.
DR BioGRID-ORCS; 16847; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Lepr; mouse.
DR PRO; PR:P48356; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P48356; protein.
DR Bgee; ENSMUSG00000057722; Expressed in placenta labyrinth and 175 other tissues.
DR ExpressionAtlas; P48356; baseline and differential.
DR Genevisible; P48356; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0038021; F:leptin receptor activity; IMP:UniProtKB.
DR GO; GO:0017046; F:peptide hormone binding; ISO:MGI.
DR GO; GO:0016500; F:protein-hormone receptor activity; ISO:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:MGI.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0098868; P:bone growth; IMP:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IGI:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0042755; P:eating behavior; ISO:MGI.
DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR GO; GO:0014009; P:glial cell proliferation; IGI:MGI.
DR GO; GO:0006094; P:gluconeogenesis; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IGI:MGI.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:1903999; P:negative regulation of eating behavior; ISO:MGI.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IMP:MGI.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; IGI:MGI.
DR GO; GO:1904060; P:negative regulation of locomotor rhythm; ISO:MGI.
DR GO; GO:0006909; P:phagocytosis; IMP:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0046850; P:regulation of bone remodeling; IMP:UniProtKB.
DR GO; GO:0060259; P:regulation of feeding behavior; IMP:UniProtKB.
DR GO; GO:0019222; P:regulation of metabolic process; TAS:MGI.
DR GO; GO:0051049; P:regulation of transport; ISO:MGI.
DR GO; GO:0044321; P:response to leptin; IMP:UniProtKB.
DR GO; GO:0019953; P:sexual reproduction; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB.
DR CDD; cd00063; FN3; 3.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR003529; Hematopoietin_rcpt_Gp130_CS.
DR InterPro; IPR003531; Hempt_rcpt_S_F1_CS.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR010457; IgC2-like_lig-bd.
DR InterPro; IPR041182; LEP-R_IGD.
DR InterPro; IPR015752; Lep_receptor.
DR PANTHER; PTHR23036:SF109; PTHR23036:SF109; 1.
DR Pfam; PF06328; Lep_receptor_Ig; 1.
DR Pfam; PF18589; ObR_Ig; 2.
DR SMART; SM00060; FN3; 4.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Obesity; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1162
FT /note="Leptin receptor"
FT /id="PRO_0000010906"
FT TOPO_DOM 22..839
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 840..860
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 861..1162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 238..331
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 329..427
FT /note="Ig-like"
FT DOMAIN 537..632
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 637..729
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 738..832
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 465..482
FT /note="Leptin-binding"
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT REGION 891..896
FT /note="Required for JAK2 activation"
FT /evidence="ECO:0000269|PubMed:12196522"
FT REGION 896..904
FT /note="Required for STAT3 phosphorylation"
FT /evidence="ECO:0000269|PubMed:11923481"
FT MOTIF 620..624
FT /note="WSXWS motif"
FT MOTIF 869..877
FT /note="Box 1 motif"
FT MOD_RES 880
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 985
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:10799542,
FT ECO:0000269|PubMed:11108838"
FT MOD_RES 1077
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11108838"
FT MOD_RES 1138
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000305|PubMed:10799542"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 668
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 695
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 698
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..90
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 89..99
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 131..142
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 186..195
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 188..193
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 350..410
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 411..416
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 434..445
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 471..526
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 486..496
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT VAR_SEQ 797..805
FT /note="DNFIPIEKY -> GMCTVLFMD (in isoform E)"
FT /evidence="ECO:0000303|PubMed:8628397"
FT /id="VSP_001703"
FT VAR_SEQ 806..1162
FT /note="Missing (in isoform E)"
FT /evidence="ECO:0000303|PubMed:8628397"
FT /id="VSP_001704"
FT VAR_SEQ 890..900
FT /note="PETFEHLFTKH -> DISFHEVFIFR (in isoform D)"
FT /evidence="ECO:0000303|PubMed:8628397"
FT /id="VSP_001701"
FT VAR_SEQ 890..894
FT /note="PETFE -> RTDTL (in isoform A)"
FT /evidence="ECO:0000303|PubMed:8548812,
FT ECO:0000303|PubMed:8628397, ECO:0000303|PubMed:8692797"
FT /id="VSP_001697"
FT VAR_SEQ 890..892
FT /note="PET -> VTV (in isoform C)"
FT /evidence="ECO:0000303|PubMed:8616721,
FT ECO:0000303|PubMed:8628397"
FT /id="VSP_001699"
FT VAR_SEQ 893..1162
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:8616721,
FT ECO:0000303|PubMed:8628397"
FT /id="VSP_001700"
FT VAR_SEQ 895..1162
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:8548812,
FT ECO:0000303|PubMed:8628397, ECO:0000303|PubMed:8692797"
FT /id="VSP_001698"
FT VAR_SEQ 901..1162
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:8628397"
FT /id="VSP_001702"
FT VARIANT 541
FT /note="V -> I (in strain: NZO)"
FT VARIANT 600
FT /note="D -> N (in strain: KK Obese)"
FT /evidence="ECO:0000269|PubMed:9845674"
FT VARIANT 651
FT /note="V -> I (in strain: NZO)"
FT VARIANT 1044
FT /note="T -> I (in strain: NZO)"
FT MUTAGEN 891
FT /note="E->A: No effect on STAT3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11923481"
FT MUTAGEN 894
FT /note="E->A: No effect on STAT3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11923481"
FT MUTAGEN 896..897
FT /note="LF->AA: Abrogates STAT3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11923481"
FT MUTAGEN 899..900
FT /note="KH->AA: No effect on STAT3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11923481"
FT MUTAGEN 902
FT /note="E->A: No effect on STAT3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11923481"
FT MUTAGEN 908
FT /note="P->A: No effect on STAT3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11923481"
FT MUTAGEN 985
FT /note="Y->L: No change in EPO-induced JAK2 activation and
FT EPO-induced tyrosine phosphorylation. No phosphorylation;
FT when associated with S-1138. No phosphorylation; when
FT associated with both S-1138 and F-1077. No change in STAT3
FT activation. No PTPN11 binding. No SOCS3 binding nor
FT inhibition of signaling. Greatly reduced ERK/FOS
FT activation. Mutants are hyperphagic, obese and
FT hyperglycaemic, females show a defect in lactation."
FT /evidence="ECO:0000269|PubMed:10799542,
FT ECO:0000269|PubMed:11018044, ECO:0000269|PubMed:12594516"
FT MUTAGEN 1077
FT /note="Y->F: No effect on EPO-induced tyrosine
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10799542"
FT MUTAGEN 1138
FT /note="Y->S: No change in EPO-induced JAK2 activation and
FT EPO-induced tyrosine phosphorylation. No phosphorylation;
FT when associated with L-985. No phosphorylation; when
FT associated with L-985 and F-1077. No STAT3 activation. No
FT change in SOCS3 binding nor signaling inhibition. No effect
FT on ERK/FOS activation."
FT /evidence="ECO:0000269|PubMed:10799542,
FT ECO:0000269|PubMed:11018044"
FT CONFLICT 140
FT /note="F -> I (in Ref. 5; AAC52705/AAC52706/AAC52707)"
FT /evidence="ECO:0000305"
FT CONFLICT 720
FT /note="A -> T (in Ref. 6; CAA71343)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1162 AA; 130789 MW; 0E1E75B076BA60A2 CRC64;
MMCQKFYVVL LHWEFLYVIA ALNLAYPISP WKFKLFCGPP NTTDDSFLSP AGAPNNASAL
KGASEAIVEA KFNSSGIYVP ELSKTVFHCC FGNEQGQNCS ALTDNTEGKT LASVVKASVF
RQLGVNWDIE CWMKGDLTLF ICHMEPLPKN PFKNYDSKVH LLYDLPEVID DSPLPPLKDS
FQTVQCNCSL RGCECHVPVP RAKLNYALLM YLEITSAGVS FQSPLMSLQP MLVVKPDPPL
GLHMEVTDDG NLKISWDSQT MAPFPLQYQV KYLENSTIVR EAAEIVSATS LLVDSVLPGS
SYEVQVRSKR LDGSGVWSDW SSPQVFTTQD VVYFPPKILT SVGSNASFHC IYKNENQIIS
SKQIVWWRNL AEKIPEIQYS IVSDRVSKVT FSNLKATRPR GKFTYDAVYC CNEQACHHRY
AELYVIDVNI NISCETDGYL TKMTCRWSPS TIQSLVGSTV QLRYHRRSLY CPDSPSIHPT
SEPKNCVLQR DGFYECVFQP IFLLSGYTMW IRINHSLGSL DSPPTCVLPD SVVKPLPPSN
VKAEITVNTG LLKVSWEKPV FPENNLQFQI RYGLSGKEIQ WKTHEVFDAK SKSASLLVSD
LCAVYVVQVR CRRLDGLGYW SNWSSPAYTL VMDVKVPMRG PEFWRKMDGD VTKKERNVTL
LWKPLTKNDS LCSVRRYVVK HRTAHNGTWS EDVGNRTNLT FLWTEPAHTV TVLAVNSLGA
SLVNFNLTFS WPMSKVSAVE SLSAYPLSSS CVILSWTLSP DDYSLLYLVI EWKILNEDDG
MKWLRIPSNV KKFYIHDNFI PIEKYQFSLY PVFMEGVGKP KIINGFTKDA IDKQQNDAGL
YVIVPIIISS CVLLLGTLLI SHQRMKKLFW DDVPNPKNCS WAQGLNFQKP ETFEHLFTKH
AESVIFGPLL LEPEPISEEI SVDTAWKNKD EMVPAAMVSL LLTTPDPESS SICISDQCNS
ANFSGSQSTQ VTCEDECQRQ PSVKYATLVS NDKLVETDEE QGFIHSPVSN CISSNHSPLR
QSFSSSSWET EAQTFFLLSD QQPTMISPQL SFSGLDELLE LEGSFPEENH REKSVCYLGV
TSVNRRESGV LLTGEAGILC TFPAQCLFSD IRILQERCSH FVENNLSLGT SGENFVPYMP
QFQTCSTHSH KIMENKMCDL TV
