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 27-MAR-2024, entry version 211. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7Z3P; X-ray; 1.94 A; B=426-633. DR PDB; 7Z3R; X-ray; 2.95 A; B=328-633. DR PDB; 8AV2; X-ray; 1.75 A; A/B=633-827. DR PDB; 8AVB; EM; 4.43 A; B/F=22-839. DR PDB; 8AVC; EM; 4.60 A; B/D/F=22-839. DR PDB; 8AVD; EM; 4.42 A; B/D/F=22-839. DR PDB; 8B7Q; EM; 4.02 A; B/F=22-839. DR PDB; 8DH8; EM; 5.90 A; A/B=22-839. DR PDB; 8DH9; EM; 4.50 A; A/B=328-839. DR PDB; 8DHA; EM; 3.80 A; A/B=330-839. DR PDBsum; 7Z3P; -. DR PDBsum; 7Z3R; -. DR PDBsum; 8AV2; -. DR PDBsum; 8AVB; -. DR PDBsum; 8AVC; -. DR PDBsum; 8AVD; -. DR PDBsum; 8B7Q; -. DR PDBsum; 8DH8; -. DR PDBsum; 8DH9; -. DR PDBsum; 8DHA; -. DR AlphaFoldDB; P48356; -. DR EMDB; EMD-15677; -. DR EMDB; EMD-15678; -. DR EMDB; EMD-15679; -. DR EMDB; EMD-15899; -. DR EMDB; EMD-27432; -. DR EMDB; EMD-27433; -. DR EMDB; EMD-27434; -. DR SMR; 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 GlyCosmos; P48356; 16 sites, No reported glycans. DR GlyGen; P48356; 16 sites. DR iPTMnet; P48356; -. DR PhosphoSitePlus; P48356; -. DR CPTAC; non-CPTAC-4044; -. DR MaxQB; P48356; -. DR PaxDb; 10090-ENSMUSP00000037385; -. DR PeptideAtlas; 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; 1098 antibodies from 44 providers. DR DNASU; 16847; -. DR Ensembl; ENSMUST00000037552.10; ENSMUSP00000037385.4; ENSMUSG00000057722.18. [P48356-1] DR Ensembl; ENSMUST00000102777.10; ENSMUSP00000099838.4; ENSMUSG00000057722.18. [P48356-3] DR Ensembl; ENSMUST00000106921.9; ENSMUSP00000102534.3; ENSMUSG00000057722.18. [P48356-2] DR GeneID; 16847; -. DR KEGG; mmu:16847; -. DR UCSC; uc008tvx.2; mouse. [P48356-1] DR UCSC; uc008twa.1; mouse. [P48356-5] DR AGR; MGI:104993; -. 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; 5344962at2759; -. DR PhylomeDB; P48356; -. DR TreeFam; TF106501; -. DR BioGRID-ORCS; 16847; 1 hit in 77 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 176 other cell types or tissues. DR ExpressionAtlas; P48356; baseline and differential. 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:0005886; C:plasma membrane; TAS: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: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; Immunoglobulins; 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 PANTHER; PTHR23036; CYTOKINE RECEPTOR; 1. DR PANTHER; PTHR23036:SF151; MYOTACTIN FORM B; 1. DR Pfam; PF06328; Lep_receptor_Ig; 1. DR Pfam; PF18589; ObR_Ig; 2. DR SMART; SM00060; FN3; 4. DR SUPFAM; SSF49265; Fibronectin type III; 4. DR PROSITE; PS50853; FN3; 3. DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR Genevisible; P48356; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond; KW Glycoprotein; Immunoglobulin domain; Membrane; Obesity; Phosphoprotein; KW Receptor; 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: KKObese)" 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" FT STRAND 330..341 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 346..354 FT /evidence="ECO:0007829|PDB:7Z3R" FT HELIX 361..363 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 364..368 FT /evidence="ECO:0007829|PDB:7Z3R" FT TURN 369..371 FT /evidence="ECO:0007829|PDB:7Z3R" FT HELIX 376..378 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 383..385 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 387..391 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 405..412 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 421..426 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 433..436 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 443..447 FT /evidence="ECO:0007829|PDB:7Z3P" FT TURN 450..454 FT /evidence="ECO:0007829|PDB:7Z3R" FT STRAND 458..470 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 494..498 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 505..515 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 518..521 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 525..527 FT /evidence="ECO:0007829|PDB:7Z3P" FT HELIX 529..532 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 539..546 FT /evidence="ECO:0007829|PDB:7Z3P" FT TURN 547..550 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 551..557 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 566..574 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 576..578 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 582..586 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 593..596 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 605..613 FT /evidence="ECO:0007829|PDB:7Z3P" FT STRAND 643..649 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 656..662 FT /evidence="ECO:0007829|PDB:8AV2" FT HELIX 667..670 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 676..683 FT /evidence="ECO:0007829|PDB:8AV2" FT TURN 684..686 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 687..694 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 697..703 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 708..716 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 726..729 FT /evidence="ECO:0007829|PDB:8AV2" FT HELIX 732..735 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 739..748 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 751..758 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 765..774 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 782..787 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 791..796 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 805..813 FT /evidence="ECO:0007829|PDB:8AV2" FT STRAND 821..825 FT /evidence="ECO:0007829|PDB:8AV2" 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 //