P42702 (LIFR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leukemia inhibitory factor receptor
Short name=LIF receptor
Short name=LIF-R

Alternative name(s):
CD_antigen=CD118

Gene names

Name:

LIFR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1097 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 (SWS) [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 component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 44

44

Potential

Chain

45 – 1097

1053

Leukemia inhibitory factor receptor

PRO_0000010902

Regions

Topological domain

45 – 833

789

Extracellular Potential

Transmembrane

834 – 858

25

Helical; Potential

Topological domain

859 – 1097

239

Cytoplasmic Potential

Domain

46 – 131

86

Fibronectin type-III 1

Domain

332 – 428

97

Fibronectin type-III 2

Domain

433 – 530

98

Fibronectin type-III 3

Domain

535 – 625

91

Fibronectin type-III 4

Domain

627 – 719

93

Fibronectin type-III 5

Domain

724 – 829

106

Fibronectin type-III 6

Motif

519 – 523

5

WSXWS motif

Motif

869 – 877

9

Box 1 motif

Amino acid modifications

Modified residue

927

1

Phosphoserine Ref.4

Glycosylation

64

1

N-linked (GlcNAc...) Potential

Glycosylation

85

1

N-linked (GlcNAc...) Potential

Glycosylation

131

1

N-linked (GlcNAc...) Ref.5

Glycosylation

143

1

N-linked (GlcNAc...) Potential

Glycosylation

191

1

N-linked (GlcNAc...) Potential

Glycosylation

243

1

N-linked (GlcNAc...) Potential

Glycosylation

303

1

N-linked (GlcNAc...) Ref.5

Glycosylation

390

1

N-linked (GlcNAc...) Potential

Glycosylation

407

1

N-linked (GlcNAc...) Ref.5

Glycosylation

426

1

N-linked (GlcNAc...) Ref.5

Glycosylation

445

1

N-linked (GlcNAc...) Potential

Glycosylation

481

1

N-linked (GlcNAc...) Potential

Glycosylation

489

1

N-linked (GlcNAc...) Potential

Glycosylation

572

1

N-linked (GlcNAc...) Potential

Glycosylation

652

1

N-linked (GlcNAc...) Potential

Glycosylation

663

1

N-linked (GlcNAc...) Potential

Glycosylation

680

1

N-linked (GlcNAc...) Potential

Glycosylation

729

1

N-linked (GlcNAc...) Potential

Glycosylation

787

1

N-linked (GlcNAc...) Potential

Disulfide bond

55 ↔ 65

Ref.5

Disulfide bond

82 ↔ 90

Ref.5

Disulfide bond

213 ↔ 270

Ref.5

Disulfide bond

341 ↔ 351

Ref.5

Disulfide bond

466 ↔ 511

Ref.5

Natural variations

Natural variant

116

1

H → Y.
Corresponds to variant rs3729734 [ dbSNP | Ensembl ].

VAR_029109

Natural variant

279

1

S → P in SWS. Ref.6

VAR_025666

Natural variant

578

1

D → N.
Corresponds to variant rs3729740 [ dbSNP | Ensembl ].

VAR_029110

Natural variant

633

1

I → M.
Corresponds to variant rs2303743 [ dbSNP | Ensembl ].

VAR_021996

Natural variant

664

1

S → L.
Corresponds to variant rs3729744 [ dbSNP | Ensembl ].

VAR_038626

Natural variant

785

1

V → I.
Corresponds to variant rs3110234 [ dbSNP | Ensembl ].

VAR_029111

Natural variant

1068

1

F → L in a colorectal cancer sample; somatic mutation. Ref.7

VAR_036166

Secondary structure

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1097

Helix Strand Turn

Details...

Beta strand

55 – 59

5

Beta strand

62 – 66

5

Beta strand

71 – 73

3

Beta strand

79 – 83

5

Beta strand

85 – 87

3

Beta strand

89 – 97

9

Beta strand

104 – 106

3

Beta strand

110 – 113

4

Beta strand

145 – 147

3

Turn

148 – 151

4

Beta strand

152 – 159

8

Helix

161 – 163

3

Beta strand

169 – 181

13

Beta strand

183 – 192

10

Helix

194 – 196

3

Beta strand

199 – 206

8

Beta strand

216 – 225

10

Beta strand

231 – 233

3

Beta strand

242 – 244

3

Beta strand

254 – 256

3

Beta strand

258 – 262

5

Beta strand

267 – 271

5

Beta strand

277 – 284

8

Beta strand

293 – 295

3

Beta strand

297 – 301

5

Beta strand

312 – 320

9

Beta strand

322 – 330

9

Beta strand

337 – 345

9

Beta strand

348 – 354

7

Helix

363 – 365

3

Beta strand

368 – 373

6

Turn

374 – 376

3

Beta strand

379 – 382

4

Beta strand

393 – 398

6

Beta strand

406 – 413

8

Beta strand

418 – 425

8

Helix

427 – 430

4

Beta strand

437 – 441

5

Beta strand

444 – 448

5

Beta strand

451 – 454

4

Beta strand

467 – 471

5

Beta strand

473 – 475

3

Beta strand

479 – 481

3

Beta strand

488 – 491

4

Beta strand

501 – 504

4

Beta strand

506 – 510

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Membrane) [UniParc]. Last modified November 1, 1995. Version 1. Checksum: C8602897E359FCE5	FASTA	1,097	123,743
	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
	Isoform 2 (Secreted) (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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 SWS 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. , 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.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X61615 mRNA. Translation: CAA43805.1.
U66563 mRNA. Translation: AAB61897.1.

IPI

IPI00444272.

PIR

S17308.

RefSeq

NP_001121143.1. NM_001127671.1.
NP_002301.1. NM_002310.5.

UniGene

Hs.133421.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3E0G	X-ray	3.10	A	52-534	[»]

ProteinModelPortal

P42702.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5770N.

MINT

MINT-1352123.

STRING

9606.ENSP00000263409.

PTM databases

PhosphoSite

P42702.

Polymorphism databases

DMDM

1170784.

Proteomic databases

PaxDb

P42702.

PRIDE

P42702.

Protocols and materials databases

DNASU

3977.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263409; ENSP00000263409; ENSG00000113594.
ENST00000453190; ENSP00000398368; ENSG00000113594.

GeneID

3977.

KEGG

hsa:3977.

UCSC

uc003jli.2. human.

Organism-specific databases

CTD

3977.

GeneCards

GC05M038475.

HGNC

HGNC:6597. LIFR.

HPA

CAB010252.

MIM

151443. gene.
601559. phenotype.

neXtProt

NX_P42702.

Orphanet

3206. Stuve-Wiedemann syndrome.

PharmGKB

PA30371.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG147644.

HOGENOM

HOG000113324.

HOVERGEN

HBG006266.

InParanoid

P42702.

KO

K05058.

OMA

IKETFYP.

OrthoDB

EOG4G7BXJ.

PhylomeDB

P42702.

Gene expression databases

ArrayExpress

P42702.

Bgee

P42702.

CleanEx

HS_LIFR.

Genevestigator

P42702.

GermOnline

ENSG00000113594. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 5 hits.

InterPro

IPR003961. Fibronectin_type3.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
[Graphical view]

Pfam

PF00041. fn3. 1 hit.
[Graphical view]

SMART

SM00060. FN3. 5 hits.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 5 hits.

PROSITE

PS50853. FN3. 6 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P42702.

GenomeRNAi

3977.

NextBio

15588.

SOURCE

Search...

Entry information

Entry name

LIFR_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.