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P48356 (LEPR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leptin receptor

Short name=LEP-R
Alternative name(s):
B219
OB receptor
Short name=OB-R
CD_antigen=CD295
Gene names
Name:Lepr
Synonyms:Db, Obr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1162 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lymphopoiesis. May play a role in reproduction. Can also mediate the ERK/FOS signaling pathway.

Isoform A may act to transport leptin to the cerebrospinal fluid By similarity.

Isoform E could function as a transport protein.

Subunit structure

On leptin stimulation, homodimerizes. The phosphorylated receptor binds a number of SH2 domain-containing proteins such as STAT3, PTPN11, and SOCS3. Interaction with SOCS3 inhibits JAK/STAT signaling.

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Isoform E: Secreted Probable.

Tissue specificity

Isoform A:highest level of expression in lung and kidney, also present in kidney, heart, brain, spleen, liver, muscle, choroid plexus and hypothalamus. Isoform B:highest level of expression in hypothalamus and lower level in brain, testes and adipose tissue. Isoform E:expressed in adipose tissue, hypothalamus, heart, and testes.

Domain

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. Ref.13

The box 1 motif is required for JAK interaction and/or activation. Ref.13

Post-translational modification

On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-985 is required for complete binding and activation of PTPN11, ERK/FOS activation and, for interaction with SOCS3. Phosphorylation on Tyr-1138 is required for STAT3 binding/activation. Ref.10 Ref.11

Phosphorylation of Tyr-985 is required for SOCS3 binding and SOCS3 mediated inhibition of leptin signaling, whereas phosphorylation of Tyr-1077 has a more accessory role.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 2 subfamily.

Contains 4 fibronectin type-III domains.

Contains 1 Ig-like (immunoglobulin-like) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BBS1Q8NFJ93EBI-6143588,EBI-1805484From a different organism.
Plcg1Q620772EBI-2257257,EBI-300133

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform B (identifier: P48356-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform A (identifier: P48356-2)

The sequence of this isoform differs from the canonical sequence as follows:
     890-894: PETFE → RTDTL
     895-1162: Missing.
Isoform C (identifier: P48356-3)

The sequence of this isoform differs from the canonical sequence as follows:
     890-892: PET → VTV
     893-1162: Missing.
Isoform D (identifier: P48356-4)

The sequence of this isoform differs from the canonical sequence as follows:
     890-900: PETFEHLFTKH → DISFHEVFIFR
     901-1162: Missing.
Isoform E (identifier: P48356-5)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 11621141Leptin receptor
PRO_0000010906

Regions

Topological domain22 – 839818Extracellular Potential
Transmembrane840 – 86021Helical; Potential
Topological domain861 – 1162302Cytoplasmic Potential
Domain238 – 33194Fibronectin type-III 1
Domain329 – 42799Ig-like
Domain537 – 63296Fibronectin type-III 2
Domain637 – 72993Fibronectin type-III 3
Domain738 – 83295Fibronectin type-III 4
Region465 – 48218Leptin-binding By similarity
Region891 – 8966Required for JAK2 activation
Motif620 – 6245WSXWS motif
Motif869 – 8779Box 1 motif

Amino acid modifications

Modified residue9851Phosphotyrosine; by JAK2 Ref.10
Modified residue10771Phosphotyrosine Ref.10
Modified residue11381Phosphotyrosine; by JAK2
Glycosylation411N-linked (GlcNAc...) Potential
Glycosylation561N-linked (GlcNAc...) Potential
Glycosylation731N-linked (GlcNAc...) Potential
Glycosylation981N-linked (GlcNAc...) Potential
Glycosylation1871N-linked (GlcNAc...) Potential
Glycosylation2751N-linked (GlcNAc...) Potential
Glycosylation3451N-linked (GlcNAc...) Potential
Glycosylation4311N-linked (GlcNAc...) Potential
Glycosylation5141N-linked (GlcNAc...) Potential
Glycosylation6221N-linked (GlcNAc...) Potential
Glycosylation6571N-linked (GlcNAc...) Potential
Glycosylation6681N-linked (GlcNAc...) Potential
Glycosylation6861N-linked (GlcNAc...) Potential
Glycosylation6951N-linked (GlcNAc...) Potential
Glycosylation6981N-linked (GlcNAc...) Potential
Glycosylation7261N-linked (GlcNAc...) Potential
Disulfide bond37 ↔ 90 By similarity
Disulfide bond89 ↔ 99 By similarity
Disulfide bond131 ↔ 142 By similarity
Disulfide bond186 ↔ 195 By similarity
Disulfide bond188 ↔ 193 By similarity
Disulfide bond350 ↔ 410 By similarity
Disulfide bond411 ↔ 416 By similarity
Disulfide bond434 ↔ 445 By similarity
Disulfide bond471 ↔ 526 By similarity
Disulfide bond486 ↔ 496 By similarity

Natural variations

Alternative sequence797 – 8059DNFIPIEKY → GMCTVLFMD in isoform E.
VSP_001703
Alternative sequence806 – 1162357Missing in isoform E.
VSP_001704
Alternative sequence890 – 90011PETFEHLFTKH → DISFHEVFIFR in isoform D.
VSP_001701
Alternative sequence890 – 8945PETFE → RTDTL in isoform A.
VSP_001697
Alternative sequence890 – 8923PET → VTV in isoform C.
VSP_001699
Alternative sequence893 – 1162270Missing in isoform C.
VSP_001700
Alternative sequence895 – 1162268Missing in isoform A.
VSP_001698
Alternative sequence901 – 1162262Missing in isoform D.
VSP_001702
Natural variant5411V → I in strain: NZO.
Natural variant6001D → N in strain: KK Obese. Ref.8
Natural variant6511V → I in strain: NZO.
Natural variant10441T → I in strain: NZO.

Experimental info

Mutagenesis9851Y → 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. Ref.11 Ref.12
Mutagenesis10771Y → F: No effect on EPO-induced tyrosine phosphorylation. Ref.11
Mutagenesis11381Y → 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. Ref.11 Ref.12
Sequence conflict1401F → I in AAC52705. Ref.5
Sequence conflict1401F → I in AAC52706. Ref.5
Sequence conflict1401F → I in AAC52707. Ref.5
Sequence conflict7201A → T in CAA71343. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform B [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: 0E1E75B076BA60A2

FASTA1,162130,789
        10         20         30         40         50         60 
MMCQKFYVVL LHWEFLYVIA ALNLAYPISP WKFKLFCGPP NTTDDSFLSP AGAPNNASAL 

        70         80         90        100        110        120 
KGASEAIVEA KFNSSGIYVP ELSKTVFHCC FGNEQGQNCS ALTDNTEGKT LASVVKASVF 

       130        140        150        160        170        180 
RQLGVNWDIE CWMKGDLTLF ICHMEPLPKN PFKNYDSKVH LLYDLPEVID DSPLPPLKDS 

       190        200        210        220        230        240 
FQTVQCNCSL RGCECHVPVP RAKLNYALLM YLEITSAGVS FQSPLMSLQP MLVVKPDPPL 

       250        260        270        280        290        300 
GLHMEVTDDG NLKISWDSQT MAPFPLQYQV KYLENSTIVR EAAEIVSATS LLVDSVLPGS 

       310        320        330        340        350        360 
SYEVQVRSKR LDGSGVWSDW SSPQVFTTQD VVYFPPKILT SVGSNASFHC IYKNENQIIS 

       370        380        390        400        410        420 
SKQIVWWRNL AEKIPEIQYS IVSDRVSKVT FSNLKATRPR GKFTYDAVYC CNEQACHHRY 

       430        440        450        460        470        480 
AELYVIDVNI NISCETDGYL TKMTCRWSPS TIQSLVGSTV QLRYHRRSLY CPDSPSIHPT 

       490        500        510        520        530        540 
SEPKNCVLQR DGFYECVFQP IFLLSGYTMW IRINHSLGSL DSPPTCVLPD SVVKPLPPSN 

       550        560        570        580        590        600 
VKAEITVNTG LLKVSWEKPV FPENNLQFQI RYGLSGKEIQ WKTHEVFDAK SKSASLLVSD 

       610        620        630        640        650        660 
LCAVYVVQVR CRRLDGLGYW SNWSSPAYTL VMDVKVPMRG PEFWRKMDGD VTKKERNVTL 

       670        680        690        700        710        720 
LWKPLTKNDS LCSVRRYVVK HRTAHNGTWS EDVGNRTNLT FLWTEPAHTV TVLAVNSLGA 

       730        740        750        760        770        780 
SLVNFNLTFS WPMSKVSAVE SLSAYPLSSS CVILSWTLSP DDYSLLYLVI EWKILNEDDG 

       790        800        810        820        830        840 
MKWLRIPSNV KKFYIHDNFI PIEKYQFSLY PVFMEGVGKP KIINGFTKDA IDKQQNDAGL 

       850        860        870        880        890        900 
YVIVPIIISS CVLLLGTLLI SHQRMKKLFW DDVPNPKNCS WAQGLNFQKP ETFEHLFTKH 

       910        920        930        940        950        960 
AESVIFGPLL LEPEPISEEI SVDTAWKNKD EMVPAAMVSL LLTTPDPESS SICISDQCNS 

       970        980        990       1000       1010       1020 
ANFSGSQSTQ VTCEDECQRQ PSVKYATLVS NDKLVETDEE QGFIHSPVSN CISSNHSPLR 

      1030       1040       1050       1060       1070       1080 
QSFSSSSWET EAQTFFLLSD QQPTMISPQL SFSGLDELLE LEGSFPEENH REKSVCYLGV 

      1090       1100       1110       1120       1130       1140 
TSVNRRESGV LLTGEAGILC TFPAQCLFSD IRILQERCSH FVENNLSLGT SGENFVPYMP 

      1150       1160 
QFQTCSTHSH KIMENKMCDL TV 

« Hide

Isoform A [UniParc].

Checksum: DF9A7A0E5AC75A53
Show »

FASTA894101,058
Isoform C [UniParc].

Checksum: 726E5C075A53C9F3
Show »

FASTA892100,771
Isoform D [UniParc].

Checksum: 7370A3C7BB5E7942
Show »

FASTA900101,863
Isoform E [UniParc].

Checksum: 591B5DE008BDB898
Show »

FASTA80590,887

References

[1]"Identification and expression cloning of a leptin receptor, OB-R."
Tartaglia L.A., Dembski M., Weng X., Deng N., Culpepper J., Devos R., Richards G.J., Campfield L.A., Clark F.T., Deeds J., Muir C., Sanker S., Moriarty A., Moore K.J., Smutko J.S., Mays G.G., Woolf E.A., Monroe C.A., Tepper R.I.
Cell 83:1263-1271(1995) [PubMed] [Europe PMC] [Abstract]
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: C57BL/KsJ.
Tissue: Hypothalamus.
[3]"Abnormal splicing of the leptin receptor in diabetic mice."
Lee G.-H., Proenca R., Montez J.M., Carroll K.M., Darvishzadeh J.G., Lee J.I., Friedman J.M.
Nature 379:632-635(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C; D AND E).
Strain: C57BL/Ks.
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/c.
Tissue: Liver.
[5]"Defective STAT signaling by the leptin receptor in diabetic mice."
Ghilardi N., Ziegler S., Wiestner A., Stoffel R., Heim M.H., Skoda R.C.
Proc. Natl. Acad. Sci. U.S.A. 93:6231-6235(1996) [PubMed] [Europe PMC] [Abstract]
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]"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.
[11]"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, STAT3 ACTIVATION, ERK/FOS ACTIVATION, MUTAGENESIS OF TYR-985; TYR-1077 AND TYR-1138.
[12]"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.
[13]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455 Genomic DNA. Translation: AAB95334.1.
AF039461 expand/collapse EMBL AC list , 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 expand/collapse EMBL AC list , AF039443, AF039444, AF039445, AF039446, AF039447, AF039448, AF039449, AF039450, AF039451, AF039452, AF039453, AF039454, AF039455, AF039456, AF039457, AF039458 Genomic DNA. Translation: AAB95335.1.
AF039460 expand/collapse EMBL AC list , 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.
PIRS68437.
S68438.
S68439.
S68440.
S68441.
RefSeqNP_001116371.1. NM_001122899.1.
NP_034834.1. NM_010704.2.
NP_666258.2. NM_146146.2.
UniGeneMm.259282.

3D structure databases

ProteinModelPortalP48356.
SMRP48356. Positions 125-324, 359-830.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201139. 3 interactions.
DIPDIP-42763N.
IntActP48356. 10 interactions.
MINTMINT-2569396.

PTM databases

PhosphoSiteP48356.

Proteomic databases

PaxDbP48356.
PRIDEP48356.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000037552; ENSMUSP00000037385; ENSMUSG00000057722. [P48356-1]
ENSMUST00000102777; ENSMUSP00000099838; ENSMUSG00000057722. [P48356-3]
ENSMUST00000106921; ENSMUSP00000102534; ENSMUSG00000057722. [P48356-2]
GeneID16847.
KEGGmmu:16847.
UCSCuc008tvx.2. mouse. [P48356-1]
uc008twa.1. mouse. [P48356-5]

Organism-specific databases

CTD3953.
MGIMGI:104993. Lepr.

Phylogenomic databases

eggNOGNOG29456.
GeneTreeENSGT00730000111209.
HOVERGENHBG000140.
InParanoidP48356.
KOK05062.
OMASWAQGLN.
OrthoDBEOG7034GB.
PhylomeDBP48356.
TreeFamTF106501.

Enzyme and pathway databases

ReactomeREACT_169390. Signaling by Leptin.
REACT_188257. Signal Transduction.

Gene expression databases

ArrayExpressP48356.
BgeeP48356.
CleanExMM_LEPR.
GenevestigatorP48356.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR003961. Fibronectin_type3.
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]
PANTHERPTHR23036:SF11. PTHR23036:SF11. 1 hit.
PfamPF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 4 hits.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
PROSITEPS50853. FN3. 3 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio290776.
PROP48356.
SOURCESearch...

Entry information

Entry nameLEPR_MOUSE
AccessionPrimary (citable) accession number: P48356
Secondary accession number(s): O35686 expand/collapse secondary AC list , O54986, Q61215, Q64309, Q9QWG3, Q9QWV5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot