Reviewed, UniProtKB/Swiss-Prot P42702 (LIFR_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cytokine and chemokine mediated signaling pathway Inferred from direct assay. Source: MGI positive regulation of cell proliferation Inferred from direct assay. Source: MGI
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	leukemia inhibitory factor receptor activity Ref.1 Inferred from direct assay. 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.

Notes: 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	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
	Glycosylation	64	1	N-linked (GlcNAc...) Potential
	Glycosylation	85	1	N-linked (GlcNAc...) Potential
	Glycosylation	131	1	N-linked (GlcNAc...) Potential
	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...) Potential
	Glycosylation	390	1	N-linked (GlcNAc...) Potential
	Glycosylation	407	1	N-linked (GlcNAc...) Potential
	Glycosylation	426	1	N-linked (GlcNAc...) Potential
	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		By similarity
	Disulfide bond	82 ↔ 90		By similarity
	Disulfide bond	213 ↔ 270		By similarity
	Disulfide bond	341 ↔ 351		By similarity
	Disulfide bond	466 ↔ 511		By similarity
Natural variations
	Natural variant	116	1	H → Y: dbSNP rs3729734.		VAR_029109
	Natural variant	279	1	S → P in SWS.		VAR_025666
	Natural variant	578	1	D → N: dbSNP rs3729740.		VAR_029110
	Natural variant	633	1	I → M: dbSNP rs2303743.		VAR_021996
	Natural variant	664	1	S → L: dbSNP rs3729744.		VAR_038626
	Natural variant	785	1	V → I: dbSNP rs3110234.		VAR_029111
	Natural variant	1068	1	F → L in a colorectal cancer sample; somatic mutation.		VAR_036166

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: 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. , 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

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

PIR

S17308.

RefSeq

NP_001121143.1.
NP_002301.1.

UniGene

Hs.133421

3D structure databases

PDBMSD

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

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5770N.

PTM databases

PhosphoSite

P42702.

Genome annotation databases

Ensembl

ENSG00000113594. Homo sapiens. [Contig view]

GeneID

3977.

KEGG

hsa:3977.

Organism-specific databases

H-InvDB

HIX0032117.

HGNC

HGNC:6597. LIFR.

HPA

CAB010252.

MIM

151443. gene.
601559. phenotype.

Orphanet

3206. Stuve-Wiedemann dysplasia.

PharmGKB

PA30371.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P42702.

HOVERGEN

P42702.

Gene expression databases

ArrayExpress

P42702.

CleanEx

HS_LIFR.

GermOnline

ENSG00000113594. Homo sapiens.

Family and domain databases

InterPro

IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003529. Hematopoietin_rcpt_gp130_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 2 hits.

Pfam

PF00041. fn3. 2 hits.
[Graphical view]

SMART

SM00060. FN3. 5 hits.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

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:	November 25, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)