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P42702 (LIFR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukemia inhibitory factor receptor

Short name=LIF receptor
Short name=LIF-R
Alternative name(s):
CD_antigen=CD118
Gene names
Name:LIFR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1097 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells.

Subunit structure

Heterodimer composed of LIFR and IL6ST. The heterodimer formed by LIFR and IL6ST interacts with the complex formed by CNTF and CNTFR. Ref.5

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein.

Isoform 2: Secreted.

Domain

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

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

Involvement in disease

Stueve-Wiedemann syndrome (STWS) [MIM:601559]: Severe autosomal recessive condition and belongs to the group of the bent-bone dysplasias. SWS is characterized by bowing of the lower limbs, with internal cortical thickening, wide metaphyses with abnormal trabecular pattern, and camptodactyly. Additional features include feeding and swallowing difficulties, as well as respiratory distress and hyperthermic episodes, which cause death in the first months of life. The rare survivors develop progressive scoliosis, spontaneous fractures, bowing of the lower limbs, with prominent joints and dysautonomia symptoms, including temperature instability, absent corneal and patellar reflexes, and smooth tongue.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

A chromosomal aberration involving LIFR is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(5;8)(p13;q12) with PLAG1.

Sequence similarities

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

Contains 6 fibronectin type-III domains.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell surface receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

ciliary neurotrophic factor-mediated signaling pathway

Inferred from direct assay PubMed 12643274. Source: BHF-UCL

cytokine-mediated signaling pathway

Inferred from direct assay PubMed 7957045. Source: MGI

leukemia inhibitory factor signaling pathway

Inferred from direct assay PubMed 12643274PubMed 8999038. Source: BHF-UCL

oncostatin-M-mediated signaling pathway

Inferred from direct assay PubMed 8999038. Source: GOC

positive regulation of cell proliferation

Inferred from direct assay PubMed 8999038. Source: BHF-UCL

response to cytokine

Inferred from direct assay PubMed 8999038. Source: BHF-UCL

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionciliary neurotrophic factor receptor binding

Inferred from physical interaction PubMed 12707266. Source: BHF-UCL

growth factor binding

Inferred from physical interaction PubMed 8999038. Source: BHF-UCL

leukemia inhibitory factor receptor activity

Inferred from direct assay PubMed 7957045. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]
Isoform 1 (identifier: P42702-1)

Also known as: Membrane;

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 2 (identifier: P42702-2)

Also known as: Secreted;

The sequence of this isoform is not available.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4444 Potential
Chain45 – 10971053Leukemia inhibitory factor receptor
PRO_0000010902

Regions

Topological domain45 – 833789Extracellular Potential
Transmembrane834 – 85825Helical; Potential
Topological domain859 – 1097239Cytoplasmic Potential
Domain49 – 13890Fibronectin type-III 1
Domain335 – 434100Fibronectin type-III 2
Domain435 – 534100Fibronectin type-III 3
Domain538 – 62992Fibronectin type-III 4
Domain627 – 71993Fibronectin type-III 5
Domain724 – 833110Fibronectin type-III 6
Motif519 – 5235WSXWS motif
Motif869 – 8779Box 1 motif

Amino acid modifications

Modified residue9271Phosphoserine Ref.4
Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation851N-linked (GlcNAc...) Potential
Glycosylation1311N-linked (GlcNAc...) Ref.5
Glycosylation1431N-linked (GlcNAc...) Potential
Glycosylation1911N-linked (GlcNAc...) Potential
Glycosylation2431N-linked (GlcNAc...) Potential
Glycosylation3031N-linked (GlcNAc...) Ref.5
Glycosylation3901N-linked (GlcNAc...) Potential
Glycosylation4071N-linked (GlcNAc...) Ref.5
Glycosylation4261N-linked (GlcNAc...) Ref.5
Glycosylation4451N-linked (GlcNAc...) Potential
Glycosylation4811N-linked (GlcNAc...) Potential
Glycosylation4891N-linked (GlcNAc...) Potential
Glycosylation5721N-linked (GlcNAc...) Potential
Glycosylation6521N-linked (GlcNAc...) Potential
Glycosylation6631N-linked (GlcNAc...) Potential
Glycosylation6801N-linked (GlcNAc...) Potential
Glycosylation7291N-linked (GlcNAc...) Potential
Glycosylation7871N-linked (GlcNAc...) Potential
Disulfide bond55 ↔ 65 Ref.5
Disulfide bond82 ↔ 90 Ref.5
Disulfide bond213 ↔ 270 Ref.5
Disulfide bond341 ↔ 351 Ref.5
Disulfide bond466 ↔ 511 Ref.5

Natural variations

Natural variant1161H → Y.
Corresponds to variant rs3729734 [ dbSNP | Ensembl ].
VAR_029109
Natural variant2791S → P in STWS. Ref.6
VAR_025666
Natural variant5781D → N.
Corresponds to variant rs3729740 [ dbSNP | Ensembl ].
VAR_029110
Natural variant6331I → M.
Corresponds to variant rs2303743 [ dbSNP | Ensembl ].
VAR_021996
Natural variant6641S → L.
Corresponds to variant rs3729744 [ dbSNP | Ensembl ].
VAR_038626
Natural variant7851V → I.
Corresponds to variant rs3110234 [ dbSNP | Ensembl ].
VAR_029111
Natural variant10681F → L in a colorectal cancer sample; somatic mutation. Ref.7
VAR_036166

Secondary structure

.......................................................................................... 1097
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Membrane) [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: C8602897E359FCE5

FASTA1,097123,743
        10         20         30         40         50         60 
MMDIYVCLKR PSWMVDNKRM RTASNFQWLL STFILLYLMN QVNSQKKGAP HDLKCVTNNL 

        70         80         90        100        110        120 
QVWNCSWKAP SGTGRGTDYE VCIENRSRSC YQLEKTSIKI PALSHGDYEI TINSLHDFGS 

       130        140        150        160        170        180 
STSKFTLNEQ NVSLIPDTPE ILNLSADFST STLYLKWNDR GSVFPHRSNV IWEIKVLRKE 

       190        200        210        220        230        240 
SMELVKLVTH NTTLNGKDTL HHWSWASDMP LECAIHFVEI RCYIDNLHFS GLEEWSDWSP 

       250        260        270        280        290        300 
VKNISWIPDS QTKVFPQDKV ILVGSDITFC CVSQEKVLSA LIGHTNCPLI HLDGENVAIK 

       310        320        330        340        350        360 
IRNISVSASS GTNVVFTTED NIFGTVIFAG YPPDTPQQLN CETHDLKEII CSWNPGRVTA 

       370        380        390        400        410        420 
LVGPRATSYT LVESFSGKYV RLKRAEAPTN ESYQLLFQML PNQEIYNFTL NAHNPLGRSQ 

       430        440        450        460        470        480 
STILVNITEK VYPHTPTSFK VKDINSTAVK LSWHLPGNFA KINFLCEIEI KKSNSVQEQR 

       490        500        510        520        530        540 
NVTIKGVENS SYLVALDKLN PYTLYTFRIR CSTETFWKWS KWSNKKQHLT TEASPSKGPD 

       550        560        570        580        590        600 
TWREWSSDGK NLIIYWKPLP INEANGKILS YNVSCSSDEE TQSLSEIPDP QHKAEIRLDK 

       610        620        630        640        650        660 
NDYIISVVAK NSVGSSPPSK IASMEIPNDD LKIEQVVGMG KGILLTWHYD PNMTCDYVIK 

       670        680        690        700        710        720 
WCNSSRSEPC LMDWRKVPSN STETVIESDE FRPGIRYNFF LYGCRNQGYQ LLRSMIGYIE 

       730        740        750        760        770        780 
ELAPIVAPNF TVEDTSADSI LVKWEDIPVE ELRGFLRGYL FYFGKGERDT SKMRVLESGR 

       790        800        810        820        830        840 
SDIKVKNITD ISQKTLRIAD LQGKTSYHLV LRAYTDGGVG PEKSMYVVTK ENSVGLIIAI 

       850        860        870        880        890        900 
LIPVAVAVIV GVVTSILCYR KREWIKETFY PDIPNPENCK ALQFQKSVCE GSSALKTLEM 

       910        920        930        940        950        960 
NPCTPNNVEV LETRSAFPKI EDTEIISPVA ERPEDRSDAE PENHVVVSYC PPIIEEEIPN 

       970        980        990       1000       1010       1020 
PAADEAGGTA QVIYIDVQSM YQPQAKPEEE QENDPVGGAG YKPQMHLPIN STVEDIAAEE 

      1030       1040       1050       1060       1070       1080 
DLDKTAGYRP QANVNTWNLV SPDSPRSIDS NSEIVSFGSP CSINSRQFLI PPKDEDSPKS 

      1090 
NGGGWSFTNF FQNKPND 

« Hide

Isoform 2 (Secreted) (Sequence not available).

References

« Hide 'large scale' references
[1]"Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130."
Gearing D.P., Thut C.J., Vanden Bos T., Gimpel S.D., Delaney P.B., King J., Price V., Cosman D., Beckmann M.P.
EMBO J. 10:2839-2848(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]"Human LIF receptor 3' non-coding region."
Wang Z., Melmed S.
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 942-1097.
[3]"The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter."
Voz M.L., Astrom A.-K., Kas K., Mark J., Stenman G., Van de Ven W.J.M.
Oncogene 16:1409-1416(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PLAG1.
[4]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-927, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex."
Skiniotis G., Lupardus P.J., Martick M., Walz T., Garcia K.C.
Mol. Cell 31:737-748(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 52-534, IDENTIFICATION IN A COMPLEX WITH IL6ST; CNTF AND CNTFR, GLYCOSYLATION AT ASN-131; ASN-303; ASN-407 AND ASN-426, DISULFIDE BONDS, ELECTRON MICROSCOPY, SUBUNIT.
[6]"Null leukemia inhibitory factor receptor (LIFR) mutations in Stueve-Wiedemann/Schwartz-Jampel type 2 syndrome."
Dagoneau N., Scheffer D., Huber C., Al-Gazali L.I., Di Rocco M., Godard A., Martinovic J., Raas-Rothschild A., Sigaudy S., Unger S., Nicole S., Fontaine B., Taupin J.-L., Moreau J.-F., Superti-Furga A., Le Merrer M., Bonaventure J., Munnich A., Legeai-Mallet L., Cormier-Daire V.
Am. J. Hum. Genet. 74:298-305(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT STWS PRO-279.
[7]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1068.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61615 mRNA. Translation: CAA43805.1.
U66563 mRNA. Translation: AAB61897.1.
PIRS17308.
RefSeqNP_001121143.1. NM_001127671.1.
NP_002301.1. NM_002310.5.
UniGeneHs.133421.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3E0GX-ray3.10A52-534[»]
ProteinModelPortalP42702.
SMRP42702. Positions 52-822.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110165. 7 interactions.
DIPDIP-5770N.
MINTMINT-1352123.
STRING9606.ENSP00000263409.

PTM databases

PhosphoSiteP42702.

Polymorphism databases

DMDM1170784.

Proteomic databases

PaxDbP42702.
PRIDEP42702.

Protocols and materials databases

DNASU3977.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263409; ENSP00000263409; ENSG00000113594. [P42702-1]
ENST00000453190; ENSP00000398368; ENSG00000113594. [P42702-1]
GeneID3977.
KEGGhsa:3977.
UCSCuc003jli.2. human. [P42702-1]

Organism-specific databases

CTD3977.
GeneCardsGC05M038475.
HGNCHGNC:6597. LIFR.
HPACAB010252.
HPA004478.
MIM151443. gene.
601559. phenotype.
neXtProtNX_P42702.
Orphanet3206. Stuve-Wiedemann syndrome.
PharmGKBPA30371.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147644.
HOGENOMHOG000113324.
HOVERGENHBG006266.
InParanoidP42702.
KOK05058.
OMAFYPDIPN.
OrthoDBEOG7V49XP.
PhylomeDBP42702.
TreeFamTF338122.

Enzyme and pathway databases

SignaLinkP42702.

Gene expression databases

ArrayExpressP42702.
BgeeP42702.
CleanExHS_LIFR.
GenevestigatorP42702.

Family and domain databases

Gene3D2.60.40.10. 5 hits.
InterProIPR003961. Fibronectin_type3.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
[Graphical view]
PfamPF00041. fn3. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 5 hits.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
PROSITEPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP42702.
GeneWikiLeukemia_inhibitory_factor_receptor.
GenomeRNAi3977.
NextBio15588.
PROP42702.
SOURCESearch...

Entry information

Entry nameLIFR_HUMAN
AccessionPrimary (citable) accession number: P42702
Secondary accession number(s): Q6LCD9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries