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Reviewed, UniProtKB/Swiss-Prot P42702 (LIFR_HUMAN)

Last modified November 25, 2008. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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)
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.

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

Defects in LIFR are the cause of Stueve-Wiedemann syndrome (SWS) [MIM:601559]; also called Schwartz-Jampel syndrome type 2 or SJS2. SWS is a 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.

A chromosomal rearrangement involving LIFR may be a cause of salivary gland pleiomorphic adenomas (PA) [181030]. Pleiomorphic adenomas are 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.

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.
Notes: 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 – 85825 Potential
Topological domain859 – 1097239Cytoplasmic Potential
Domain46 – 13186Fibronectin type-III 1
Domain332 – 42897Fibronectin type-III 2
Domain433 – 53098Fibronectin type-III 3
Domain535 – 62591Fibronectin type-III 4
Domain627 – 71993Fibronectin type-III 5
Domain724 – 829106Fibronectin type-III 6
Motif519 – 5235WSXWS motif
Motif869 – 8779Box 1 motif

Amino acid modifications

Modified residue9271Phosphoserine
Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation851N-linked (GlcNAc...) Potential
Glycosylation1311N-linked (GlcNAc...) Potential
Glycosylation1431N-linked (GlcNAc...) Potential
Glycosylation1911N-linked (GlcNAc...) Potential
Glycosylation2431N-linked (GlcNAc...) Potential
Glycosylation3031N-linked (GlcNAc...) Potential
Glycosylation3901N-linked (GlcNAc...) Potential
Glycosylation4071N-linked (GlcNAc...) Potential
Glycosylation4261N-linked (GlcNAc...) Potential
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 By similarity
Disulfide bond82 ↔ 90 By similarity
Disulfide bond213 ↔ 270 By similarity
Disulfide bond341 ↔ 351 By similarity
Disulfide bond466 ↔ 511 By similarity

Natural variations

Natural variant1161H → Y: dbSNP rs3729734.
VAR_029109
Natural variant2791S → P in SWS.
VAR_025666
Natural variant5781D → N: dbSNP rs3729740.
VAR_029110
Natural variant6331I → M: dbSNP rs2303743.
VAR_021996
Natural variant6641S → L: dbSNP rs3729744.
VAR_038626
Natural variant7851V → I: dbSNP rs3110234.
VAR_029111
Natural variant10681F → L in a colorectal cancer sample; somatic mutation.
VAR_036166

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: 1915266] [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: 9525740] [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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-927, MASS SPECTROMETRY.
[5]"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: 14740318] [Abstract]
Cited for: VARIANT SWS PRO-279.
[6]"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: 16959974] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1068.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

X61615 mRNA. Translation: CAA43805.1.
U66563 mRNA. Translation: AAB61897.1.
PIRS17308.
RefSeqNP_001121143.1.
NP_002301.1.
UniGeneHs.133421

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
3E0GX-ray3.10A52-534[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:5770N.

PTM databases

PhosphoSiteP42702.

Genome annotation databases

EnsemblENSG00000113594. Homo sapiens. [Contig view]
GeneID3977.
KEGGhsa:3977.

Organism-specific databases

H-InvDBHIX0032117.
HGNCHGNC:6597. LIFR.
HPACAB010252.
MIM151443. gene.
601559. phenotype.
Orphanet3206. Stuve-Wiedemann dysplasia.
PharmGKBPA30371.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP42702.
HOVERGENP42702.

Gene expression databases

ArrayExpressP42702.
CleanExHS_LIFR.
GermOnlineENSG00000113594. Homo sapiens.

Family and domain databases

InterProIPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003529. Hematopoietin_rcpt_gp130_CS.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 2 hits.
PfamPF00041. fn3. 2 hits.
[Graphical view]
SMARTSM00060. FN3. 5 hits.
[Graphical view]
PROSITEPS50853. FN3. 6 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio15588.
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: November 25, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human cell differentiation molecules

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

Human chromosome 5

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents