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P42702

- LIFR_HUMAN

UniProt

P42702 - LIFR_HUMAN

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Protein

Leukemia inhibitory factor receptor

Gene
LIFR
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. ciliary neurotrophic factor receptor binding Source: BHF-UCL
  2. growth factor binding Source: BHF-UCL
  3. leukemia inhibitory factor receptor activity Source: MGI

GO - Biological processi

  1. cell surface receptor signaling pathway Source: ProtInc
  2. ciliary neurotrophic factor-mediated signaling pathway Source: BHF-UCL
  3. cytokine-mediated signaling pathway Source: MGI
  4. leukemia inhibitory factor signaling pathway Source: BHF-UCL
  5. oncostatin-M-mediated signaling pathway Source: GOC
  6. positive regulation of cell proliferation Source: BHF-UCL
  7. response to cytokine Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

SignaLinkiP42702.

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
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:6597. LIFR.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini45 – 833789Extracellular Reviewed predictionAdd
BLAST
Transmembranei834 – 85825Helical; Reviewed predictionAdd
BLAST
Topological domaini859 – 1097239Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
  2. integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti279 – 2791S → P in STWS. 1 Publication
VAR_025666
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

MIMi601559. phenotype.
Orphaneti3206. Stuve-Wiedemann syndrome.
PharmGKBiPA30371.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4444 Reviewed predictionAdd
BLAST
Chaini45 – 10971053Leukemia inhibitory factor receptorPRO_0000010902Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi55 ↔ 651 Publication
Glycosylationi64 – 641N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi82 ↔ 901 Publication
Glycosylationi85 – 851N-linked (GlcNAc...) Reviewed prediction
Glycosylationi131 – 1311N-linked (GlcNAc...)1 Publication
Glycosylationi143 – 1431N-linked (GlcNAc...) Reviewed prediction
Glycosylationi191 – 1911N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi213 ↔ 2701 Publication
Glycosylationi243 – 2431N-linked (GlcNAc...) Reviewed prediction
Glycosylationi303 – 3031N-linked (GlcNAc...)1 Publication
Disulfide bondi341 ↔ 3511 Publication
Glycosylationi390 – 3901N-linked (GlcNAc...) Reviewed prediction
Glycosylationi407 – 4071N-linked (GlcNAc...)1 Publication
Glycosylationi426 – 4261N-linked (GlcNAc...)1 Publication
Glycosylationi445 – 4451N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi466 ↔ 5111 Publication
Glycosylationi481 – 4811N-linked (GlcNAc...) Reviewed prediction
Glycosylationi489 – 4891N-linked (GlcNAc...) Reviewed prediction
Glycosylationi572 – 5721N-linked (GlcNAc...) Reviewed prediction
Glycosylationi652 – 6521N-linked (GlcNAc...) Reviewed prediction
Glycosylationi663 – 6631N-linked (GlcNAc...) Reviewed prediction
Glycosylationi680 – 6801N-linked (GlcNAc...) Reviewed prediction
Glycosylationi729 – 7291N-linked (GlcNAc...) Reviewed prediction
Glycosylationi787 – 7871N-linked (GlcNAc...) Reviewed prediction
Modified residuei927 – 9271Phosphoserine1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP42702.
PaxDbiP42702.
PRIDEiP42702.

PTM databases

PhosphoSiteiP42702.

Expressioni

Gene expression databases

ArrayExpressiP42702.
BgeeiP42702.
CleanExiHS_LIFR.
GenevestigatoriP42702.

Organism-specific databases

HPAiCAB010252.
HPA004478.

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

Protein-protein interaction databases

BioGridi110165. 7 interactions.
DIPiDIP-5770N.
MINTiMINT-1352123.
STRINGi9606.ENSP00000263409.

Structurei

Secondary structure

1
1097
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi55 – 595
Beta strandi62 – 665
Beta strandi71 – 733
Beta strandi79 – 835
Beta strandi85 – 873
Beta strandi89 – 979
Beta strandi104 – 1063
Beta strandi110 – 1134
Beta strandi145 – 1473
Turni148 – 1514
Beta strandi152 – 1598
Helixi161 – 1633
Beta strandi169 – 18113
Beta strandi183 – 19210
Helixi194 – 1963
Beta strandi199 – 2068
Beta strandi216 – 22510
Beta strandi231 – 2333
Beta strandi242 – 2443
Beta strandi254 – 2563
Beta strandi258 – 2625
Beta strandi267 – 2715
Beta strandi277 – 2848
Beta strandi293 – 2953
Beta strandi297 – 3015
Beta strandi312 – 3209
Beta strandi322 – 3309
Beta strandi337 – 3459
Beta strandi348 – 3547
Helixi363 – 3653
Beta strandi368 – 3736
Turni374 – 3763
Beta strandi379 – 3824
Beta strandi393 – 3986
Beta strandi406 – 4138
Beta strandi418 – 4258
Helixi427 – 4304
Beta strandi437 – 4415
Beta strandi444 – 4485
Beta strandi451 – 4544
Beta strandi467 – 4715
Beta strandi473 – 4753
Beta strandi479 – 4813
Beta strandi488 – 4914
Beta strandi501 – 5044
Beta strandi506 – 5105

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3E0GX-ray3.10A52-534[»]
ProteinModelPortaliP42702.
SMRiP42702. Positions 52-822.

Miscellaneous databases

EvolutionaryTraceiP42702.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini49 – 13890Fibronectin type-III 1Add
BLAST
Domaini335 – 434100Fibronectin type-III 2Add
BLAST
Domaini435 – 534100Fibronectin type-III 3Add
BLAST
Domaini538 – 62992Fibronectin type-III 4Add
BLAST
Domaini627 – 71993Fibronectin type-III 5Add
BLAST
Domaini724 – 833110Fibronectin type-III 6Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi519 – 5235WSXWS motif
Motifi869 – 8779Box 1 motif

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

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG147644.
HOGENOMiHOG000113324.
HOVERGENiHBG006266.
InParanoidiP42702.
KOiK05058.
OMAiFYPDIPN.
OrthoDBiEOG7V49XP.
PhylomeDBiP42702.
TreeFamiTF338122.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. Fibronectin_type3.
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. Align

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

MMDIYVCLKR PSWMVDNKRM RTASNFQWLL STFILLYLMN QVNSQKKGAP     50
HDLKCVTNNL QVWNCSWKAP SGTGRGTDYE VCIENRSRSC YQLEKTSIKI 100
PALSHGDYEI TINSLHDFGS STSKFTLNEQ NVSLIPDTPE ILNLSADFST 150
STLYLKWNDR GSVFPHRSNV IWEIKVLRKE SMELVKLVTH NTTLNGKDTL 200
HHWSWASDMP LECAIHFVEI RCYIDNLHFS GLEEWSDWSP VKNISWIPDS 250
QTKVFPQDKV ILVGSDITFC CVSQEKVLSA LIGHTNCPLI HLDGENVAIK 300
IRNISVSASS GTNVVFTTED NIFGTVIFAG YPPDTPQQLN CETHDLKEII 350
CSWNPGRVTA LVGPRATSYT LVESFSGKYV RLKRAEAPTN ESYQLLFQML 400
PNQEIYNFTL NAHNPLGRSQ STILVNITEK VYPHTPTSFK VKDINSTAVK 450
LSWHLPGNFA KINFLCEIEI KKSNSVQEQR NVTIKGVENS SYLVALDKLN 500
PYTLYTFRIR CSTETFWKWS KWSNKKQHLT TEASPSKGPD TWREWSSDGK 550
NLIIYWKPLP INEANGKILS YNVSCSSDEE TQSLSEIPDP QHKAEIRLDK 600
NDYIISVVAK NSVGSSPPSK IASMEIPNDD LKIEQVVGMG KGILLTWHYD 650
PNMTCDYVIK WCNSSRSEPC LMDWRKVPSN STETVIESDE FRPGIRYNFF 700
LYGCRNQGYQ LLRSMIGYIE ELAPIVAPNF TVEDTSADSI LVKWEDIPVE 750
ELRGFLRGYL FYFGKGERDT SKMRVLESGR SDIKVKNITD ISQKTLRIAD 800
LQGKTSYHLV LRAYTDGGVG PEKSMYVVTK ENSVGLIIAI LIPVAVAVIV 850
GVVTSILCYR KREWIKETFY PDIPNPENCK ALQFQKSVCE GSSALKTLEM 900
NPCTPNNVEV LETRSAFPKI EDTEIISPVA ERPEDRSDAE PENHVVVSYC 950
PPIIEEEIPN PAADEAGGTA QVIYIDVQSM YQPQAKPEEE QENDPVGGAG 1000
YKPQMHLPIN STVEDIAAEE DLDKTAGYRP QANVNTWNLV SPDSPRSIDS 1050
NSEIVSFGSP CSINSRQFLI PPKDEDSPKS NGGGWSFTNF FQNKPND 1097
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti116 – 1161H → Y.
Corresponds to variant rs3729734 [ dbSNP | Ensembl ].
VAR_029109
Natural varianti279 – 2791S → P in STWS. 1 Publication
VAR_025666
Natural varianti578 – 5781D → N.
Corresponds to variant rs3729740 [ dbSNP | Ensembl ].
VAR_029110
Natural varianti633 – 6331I → M.
Corresponds to variant rs2303743 [ dbSNP | Ensembl ].
VAR_021996
Natural varianti664 – 6641S → L.
Corresponds to variant rs3729744 [ dbSNP | Ensembl ].
VAR_038626
Natural varianti785 – 7851V → I.
Corresponds to variant rs3110234 [ dbSNP | Ensembl ].
VAR_029111
Natural varianti1068 – 10681F → L in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036166

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
UniGeneiHs.133421.

Genome annotation databases

EnsembliENST00000263409; ENSP00000263409; ENSG00000113594. [P42702-1]
ENST00000453190; ENSP00000398368; ENSG00000113594. [P42702-1]
GeneIDi3977.
KEGGihsa:3977.
UCSCiuc003jli.2. human. [P42702-1]

Polymorphism databases

DMDMi1170784.

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:
EMBL
GenBank
DDBJ
Links Updated
X61615 mRNA. Translation: CAA43805.1 .
U66563 mRNA. Translation: AAB61897.1 .
CCDSi CCDS3927.1. [P42702-1 ]
PIRi S17308.
RefSeqi NP_001121143.1. NM_001127671.1. [P42702-1 ]
NP_002301.1. NM_002310.5. [P42702-1 ]
UniGenei Hs.133421.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3E0G X-ray 3.10 A 52-534 [» ]
ProteinModelPortali P42702.
SMRi P42702. Positions 52-822.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110165. 7 interactions.
DIPi DIP-5770N.
MINTi MINT-1352123.
STRINGi 9606.ENSP00000263409.

PTM databases

PhosphoSitei P42702.

Polymorphism databases

DMDMi 1170784.

Proteomic databases

MaxQBi P42702.
PaxDbi P42702.
PRIDEi P42702.

Protocols and materials databases

DNASUi 3977.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000263409 ; ENSP00000263409 ; ENSG00000113594 . [P42702-1 ]
ENST00000453190 ; ENSP00000398368 ; ENSG00000113594 . [P42702-1 ]
GeneIDi 3977.
KEGGi hsa:3977.
UCSCi uc003jli.2. human. [P42702-1 ]

Organism-specific databases

CTDi 3977.
GeneCardsi GC05M038475.
HGNCi HGNC:6597. LIFR.
HPAi CAB010252.
HPA004478.
MIMi 151443. gene.
601559. phenotype.
neXtProti NX_P42702.
Orphaneti 3206. Stuve-Wiedemann syndrome.
PharmGKBi PA30371.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG147644.
HOGENOMi HOG000113324.
HOVERGENi HBG006266.
InParanoidi P42702.
KOi K05058.
OMAi FYPDIPN.
OrthoDBi EOG7V49XP.
PhylomeDBi P42702.
TreeFami TF338122.

Enzyme and pathway databases

SignaLinki P42702.

Miscellaneous databases

EvolutionaryTracei P42702.
GeneWikii Leukemia_inhibitory_factor_receptor.
GenomeRNAii 3977.
NextBioi 15588.
PROi P42702.
SOURCEi Search...

Gene expression databases

ArrayExpressi P42702.
Bgeei P42702.
CleanExi HS_LIFR.
Genevestigatori P42702.

Family and domain databases

Gene3Di 2.60.40.10. 5 hits.
InterProi IPR003961. Fibronectin_type3.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
[Graphical view ]
Pfami PF00041. fn3. 1 hit.
[Graphical view ]
SMARTi SM00060. FN3. 5 hits.
[Graphical view ]
SUPFAMi SSF49265. SSF49265. 4 hits.
PROSITEi PS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: VARIANT STWS PRO-279.
  7. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1068.

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: July 9, 2014
This is version 141 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

External Data

Dasty 3

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