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Protein

Leukemia inhibitory factor receptor

Gene

LIFR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • ciliary neurotrophic factor receptor binding Source: BHF-UCL
  • growth factor binding Source: BHF-UCL
  • leukemia inhibitory factor receptor activity Source: MGI

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • ciliary neurotrophic factor-mediated signaling pathway Source: BHF-UCL
  • cytokine-mediated signaling pathway Source: MGI
  • leukemia inhibitory factor signaling pathway Source: BHF-UCL
  • oncostatin-M-mediated signaling pathway Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • response to cytokine Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113594-MONOMER.
ReactomeiR-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
SignaLinkiP42702.
SIGNORiP42702.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukemia inhibitory factor receptor
Short name:
LIF receptor
Short name:
LIF-R
Alternative name(s):
CD_antigen: CD118
Gene namesi
Name:LIFR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6597. LIFR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini45 – 833ExtracellularSequence analysisAdd BLAST789
Transmembranei834 – 858HelicalSequence analysisAdd BLAST25
Topological domaini859 – 1097CytoplasmicSequence analysisAdd BLAST239

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Stueve-Wiedemann syndrome (STWS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSevere 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.
See also OMIM:601559
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025666279S → P in STWS. 1 Publication1

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.

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3977.
MalaCardsiLIFR.
MIMi601559. phenotype.
OpenTargetsiENSG00000113594.
Orphaneti3206. Stuve-Wiedemann syndrome.
PharmGKBiPA30371.

Polymorphism and mutation databases

BioMutaiLIFR.
DMDMi1170784.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 44Sequence analysisAdd BLAST44
ChainiPRO_000001090245 – 1097Leukemia inhibitory factor receptorAdd BLAST1053

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi55 ↔ 651 Publication
Glycosylationi64N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi82 ↔ 901 Publication
Glycosylationi85N-linked (GlcNAc...)Sequence analysis1
Glycosylationi131N-linked (GlcNAc...)1 Publication1
Glycosylationi143N-linked (GlcNAc...)Sequence analysis1
Glycosylationi191N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi213 ↔ 2701 Publication
Glycosylationi243N-linked (GlcNAc...)Sequence analysis1
Glycosylationi303N-linked (GlcNAc...)1 Publication1
Disulfide bondi341 ↔ 3511 Publication
Glycosylationi390N-linked (GlcNAc...)Sequence analysis1
Glycosylationi407N-linked (GlcNAc...)1 Publication1
Glycosylationi426N-linked (GlcNAc...)1 Publication1
Glycosylationi445N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi466 ↔ 5111 Publication
Glycosylationi481N-linked (GlcNAc...)Sequence analysis1
Glycosylationi489N-linked (GlcNAc...)Sequence analysis1
Glycosylationi572N-linked (GlcNAc...)Sequence analysis1
Glycosylationi652N-linked (GlcNAc...)Sequence analysis1
Glycosylationi663N-linked (GlcNAc...)Sequence analysis1
Glycosylationi680N-linked (GlcNAc...)Sequence analysis1
Glycosylationi729N-linked (GlcNAc...)Sequence analysis1
Glycosylationi787N-linked (GlcNAc...)Sequence analysis1
Modified residuei927PhosphoserineCombined sources1
Modified residuei1044PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP42702.
PaxDbiP42702.
PeptideAtlasiP42702.
PRIDEiP42702.

PTM databases

iPTMnetiP42702.
PhosphoSitePlusiP42702.

Expressioni

Gene expression databases

BgeeiENSG00000113594.
CleanExiHS_LIFR.
ExpressionAtlasiP42702. baseline and differential.
GenevisibleiP42702. HS.

Organism-specific databases

HPAiCAB010252.
HPA004478.
HPA064147.

Interactioni

Subunit structurei

Heterodimer composed of LIFR and IL6ST. The heterodimer formed by LIFR and IL6ST interacts with the complex formed by CNTF and CNTFR.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CNTFP264419EBI-7702162,EBI-1050897

GO - Molecular functioni

  • ciliary neurotrophic factor receptor binding Source: BHF-UCL
  • growth factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110165. 14 interactors.
DIPiDIP-5770N.
IntActiP42702. 8 interactors.
MINTiMINT-1352123.
STRINGi9606.ENSP00000263409.

Structurei

Secondary structure

11097
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi55 – 59Combined sources5
Beta strandi62 – 66Combined sources5
Beta strandi71 – 73Combined sources3
Beta strandi79 – 83Combined sources5
Beta strandi85 – 87Combined sources3
Beta strandi89 – 97Combined sources9
Beta strandi104 – 106Combined sources3
Beta strandi110 – 113Combined sources4
Beta strandi145 – 147Combined sources3
Turni148 – 151Combined sources4
Beta strandi152 – 159Combined sources8
Helixi161 – 163Combined sources3
Beta strandi169 – 181Combined sources13
Beta strandi183 – 192Combined sources10
Helixi194 – 196Combined sources3
Beta strandi199 – 206Combined sources8
Beta strandi216 – 225Combined sources10
Beta strandi231 – 233Combined sources3
Beta strandi242 – 244Combined sources3
Beta strandi254 – 256Combined sources3
Beta strandi258 – 262Combined sources5
Beta strandi267 – 271Combined sources5
Beta strandi277 – 284Combined sources8
Beta strandi293 – 295Combined sources3
Beta strandi297 – 301Combined sources5
Beta strandi312 – 320Combined sources9
Beta strandi322 – 330Combined sources9
Beta strandi337 – 345Combined sources9
Beta strandi348 – 354Combined sources7
Helixi363 – 365Combined sources3
Beta strandi368 – 373Combined sources6
Turni374 – 376Combined sources3
Beta strandi379 – 382Combined sources4
Beta strandi393 – 398Combined sources6
Beta strandi406 – 413Combined sources8
Beta strandi418 – 425Combined sources8
Helixi427 – 430Combined sources4
Beta strandi437 – 441Combined sources5
Beta strandi444 – 448Combined sources5
Beta strandi451 – 454Combined sources4
Beta strandi467 – 471Combined sources5
Beta strandi473 – 475Combined sources3
Beta strandi479 – 481Combined sources3
Beta strandi488 – 491Combined sources4
Beta strandi501 – 504Combined sources4
Beta strandi506 – 510Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3E0GX-ray3.10A52-534[»]
ProteinModelPortaliP42702.
SMRiP42702.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42702.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini49 – 138Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST90
Domaini335 – 434Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST100
Domaini435 – 534Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST100
Domaini538 – 629Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST92
Domaini627 – 719Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST93
Domaini724 – 833Fibronectin type-III 6PROSITE-ProRule annotationAdd BLAST110

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi519 – 523WSXWS motif5
Motifi869 – 877Box 1 motif9

Domaini

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.

Sequence similaritiesi

Contains 6 fibronectin type-III domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF1V. Eukaryota.
ENOG410ZMDF. LUCA.
GeneTreeiENSGT00550000074436.
HOGENOMiHOG000113324.
HOVERGENiHBG006266.
InParanoidiP42702.
KOiK05058.
OMAiFYPDIPN.
OrthoDBiEOG091G00RF.
PhylomeDBiP42702.
TreeFamiTF338122.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 5 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P42702-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MMDIYVCLKR PSWMVDNKRM RTASNFQWLL STFILLYLMN QVNSQKKGAP
60 70 80 90 100
HDLKCVTNNL QVWNCSWKAP SGTGRGTDYE VCIENRSRSC YQLEKTSIKI
110 120 130 140 150
PALSHGDYEI TINSLHDFGS STSKFTLNEQ NVSLIPDTPE ILNLSADFST
160 170 180 190 200
STLYLKWNDR GSVFPHRSNV IWEIKVLRKE SMELVKLVTH NTTLNGKDTL
210 220 230 240 250
HHWSWASDMP LECAIHFVEI RCYIDNLHFS GLEEWSDWSP VKNISWIPDS
260 270 280 290 300
QTKVFPQDKV ILVGSDITFC CVSQEKVLSA LIGHTNCPLI HLDGENVAIK
310 320 330 340 350
IRNISVSASS GTNVVFTTED NIFGTVIFAG YPPDTPQQLN CETHDLKEII
360 370 380 390 400
CSWNPGRVTA LVGPRATSYT LVESFSGKYV RLKRAEAPTN ESYQLLFQML
410 420 430 440 450
PNQEIYNFTL NAHNPLGRSQ STILVNITEK VYPHTPTSFK VKDINSTAVK
460 470 480 490 500
LSWHLPGNFA KINFLCEIEI KKSNSVQEQR NVTIKGVENS SYLVALDKLN
510 520 530 540 550
PYTLYTFRIR CSTETFWKWS KWSNKKQHLT TEASPSKGPD TWREWSSDGK
560 570 580 590 600
NLIIYWKPLP INEANGKILS YNVSCSSDEE TQSLSEIPDP QHKAEIRLDK
610 620 630 640 650
NDYIISVVAK NSVGSSPPSK IASMEIPNDD LKIEQVVGMG KGILLTWHYD
660 670 680 690 700
PNMTCDYVIK WCNSSRSEPC LMDWRKVPSN STETVIESDE FRPGIRYNFF
710 720 730 740 750
LYGCRNQGYQ LLRSMIGYIE ELAPIVAPNF TVEDTSADSI LVKWEDIPVE
760 770 780 790 800
ELRGFLRGYL FYFGKGERDT SKMRVLESGR SDIKVKNITD ISQKTLRIAD
810 820 830 840 850
LQGKTSYHLV LRAYTDGGVG PEKSMYVVTK ENSVGLIIAI LIPVAVAVIV
860 870 880 890 900
GVVTSILCYR KREWIKETFY PDIPNPENCK ALQFQKSVCE GSSALKTLEM
910 920 930 940 950
NPCTPNNVEV LETRSAFPKI EDTEIISPVA ERPEDRSDAE PENHVVVSYC
960 970 980 990 1000
PPIIEEEIPN PAADEAGGTA QVIYIDVQSM YQPQAKPEEE QENDPVGGAG
1010 1020 1030 1040 1050
YKPQMHLPIN STVEDIAAEE DLDKTAGYRP QANVNTWNLV SPDSPRSIDS
1060 1070 1080 1090
NSEIVSFGSP CSINSRQFLI PPKDEDSPKS NGGGWSFTNF FQNKPND
Length:1,097
Mass (Da):123,743
Last modified:November 1, 1995 - v1
Checksum:iC8602897E359FCE5
GO
Isoform 2 (identifier: P42702-2)
Also known as: Secreted
Sequence is not available
Note: No experimental confirmation available.
Length:
Mass (Da):

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029109116H → Y.Corresponds to variant rs3729734dbSNPEnsembl.1
Natural variantiVAR_025666279S → P in STWS. 1 Publication1
Natural variantiVAR_029110578D → N.Corresponds to variant rs3729740dbSNPEnsembl.1
Natural variantiVAR_021996633I → M.Corresponds to variant rs2303743dbSNPEnsembl.1
Natural variantiVAR_038626664S → L.Corresponds to variant rs3729744dbSNPEnsembl.1
Natural variantiVAR_029111785V → I.Corresponds to variant rs3110234dbSNPEnsembl.1
Natural variantiVAR_0361661068F → L in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61615 mRNA. Translation: CAA43805.1.
U66563 mRNA. Translation: AAB61897.1.
CCDSiCCDS3927.1. [P42702-1]
PIRiS17308.
RefSeqiNP_001121143.1. NM_001127671.1. [P42702-1]
NP_002301.1. NM_002310.5. [P42702-1]
XP_011512342.1. XM_011514040.2. [P42702-1]
XP_011512344.1. XM_011514042.2. [P42702-1]
XP_016864952.1. XM_017009463.1. [P42702-1]
UniGeneiHs.133421.
Hs.657602.

Genome annotation databases

EnsembliENST00000263409; ENSP00000263409; ENSG00000113594. [P42702-1]
ENST00000453190; ENSP00000398368; ENSG00000113594. [P42702-1]
GeneIDi3977.
KEGGihsa:3977.
UCSCiuc003jli.3. human. [P42702-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61615 mRNA. Translation: CAA43805.1.
U66563 mRNA. Translation: AAB61897.1.
CCDSiCCDS3927.1. [P42702-1]
PIRiS17308.
RefSeqiNP_001121143.1. NM_001127671.1. [P42702-1]
NP_002301.1. NM_002310.5. [P42702-1]
XP_011512342.1. XM_011514040.2. [P42702-1]
XP_011512344.1. XM_011514042.2. [P42702-1]
XP_016864952.1. XM_017009463.1. [P42702-1]
UniGeneiHs.133421.
Hs.657602.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3E0GX-ray3.10A52-534[»]
ProteinModelPortaliP42702.
SMRiP42702.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110165. 14 interactors.
DIPiDIP-5770N.
IntActiP42702. 8 interactors.
MINTiMINT-1352123.
STRINGi9606.ENSP00000263409.

PTM databases

iPTMnetiP42702.
PhosphoSitePlusiP42702.

Polymorphism and mutation databases

BioMutaiLIFR.
DMDMi1170784.

Proteomic databases

EPDiP42702.
PaxDbiP42702.
PeptideAtlasiP42702.
PRIDEiP42702.

Protocols and materials databases

DNASUi3977.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263409; ENSP00000263409; ENSG00000113594. [P42702-1]
ENST00000453190; ENSP00000398368; ENSG00000113594. [P42702-1]
GeneIDi3977.
KEGGihsa:3977.
UCSCiuc003jli.3. human. [P42702-1]

Organism-specific databases

CTDi3977.
DisGeNETi3977.
GeneCardsiLIFR.
HGNCiHGNC:6597. LIFR.
HPAiCAB010252.
HPA004478.
HPA064147.
MalaCardsiLIFR.
MIMi151443. gene.
601559. phenotype.
neXtProtiNX_P42702.
OpenTargetsiENSG00000113594.
Orphaneti3206. Stuve-Wiedemann syndrome.
PharmGKBiPA30371.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF1V. Eukaryota.
ENOG410ZMDF. LUCA.
GeneTreeiENSGT00550000074436.
HOGENOMiHOG000113324.
HOVERGENiHBG006266.
InParanoidiP42702.
KOiK05058.
OMAiFYPDIPN.
OrthoDBiEOG091G00RF.
PhylomeDBiP42702.
TreeFamiTF338122.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113594-MONOMER.
ReactomeiR-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
SignaLinkiP42702.
SIGNORiP42702.

Miscellaneous databases

ChiTaRSiLIFR. human.
EvolutionaryTraceiP42702.
GeneWikiiLeukemia_inhibitory_factor_receptor.
GenomeRNAii3977.
PROiP42702.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113594.
CleanExiHS_LIFR.
ExpressionAtlasiP42702. baseline and differential.
GenevisibleiP42702. HS.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 5 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLIFR_HUMAN
AccessioniPrimary (citable) accession number: P42702
Secondary accession number(s): Q6LCD9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 165 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.