Reviewed, UniProtKB/Swiss-Prot P15018 (LIF_HUMAN)

Names and origin

Protein names

Recommended name:
    Leukemia inhibitory factor
      Short name=LIF
Alternative name(s):
    Differentiation-stimulating factor
      Short name=D factor
    Melanoma-derived LPL inhibitor
      Short name=MLPLI
    INN=Emfilermin

Gene names

Name:	LIF
Synonyms:	HILDA

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	202 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	LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.
Subcellular location	Secreted.
Pharmaceutical use	In phase II clinical trial. The drug is being developed by Amrad to assist embryo implantation in women who have failed to become pregnant despite assisted reproductive technologies (ART).
Sequence similarities	Belongs to the LIF/OSM family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	immune response Inferred from electronic annotation. Source: InterPro leukemia inhibitory factor signaling pathway Inferred from direct assay. Source: UniProtKB multicellular organismal development Ref.1 Traceable author statement. Source: ProtInc negative regulation of hormone secretion Inferred from direct assay. Source: MGI positive regulation of MAPKKK cascade Inferred from direct assay. Source: MGI positive regulation of cell proliferation Ref.1 Inferred from direct assay. Source: UniProtKB positive regulation of macrophage differentiation Inferred from direct assay. Source: MGI positive regulation of peptidyl-serine phosphorylation Inferred from direct assay. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Inferred by curator. Source: UniProtKB
Molecular function	cytokine activity Inferred from direct assay. Source: MGI growth factor activity Inferred from direct assay. Source: UniProtKB leukemia inhibitory factor receptor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.7

Chain

23 – 202

180

Leukemia inhibitory factor

PRO_0000017715

Amino acid modifications

Glycosylation

31

1

N-linked (GlcNAc...) Ref.8

Glycosylation

56

1

N-linked (GlcNAc...) Ref.8

Glycosylation

85

1

N-linked (GlcNAc...) Ref.8

Glycosylation

95

1

N-linked (GlcNAc...) Ref.8

Glycosylation

118

1

N-linked (GlcNAc...) Ref.8

Glycosylation

138

1

N-linked (GlcNAc...) Ref.8

Disulfide bond

34 ↔ 156

Ref.8

Disulfide bond

40 ↔ 153

Ref.8

Disulfide bond

82 ↔ 185

Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

202

Helix Strand Turn

Details...

Helix

44 – 70

27

Turn

72 – 77

6

Helix

78 – 81

4

Helix

98 – 126

29

Helix

131 – 157

27

Helix

177 – 199

23

Sequences

	Sequence		Length	Mass (Da)
	P15018-1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 634CD10BFF67A217	FASTA	202	22,008
	10 20 30 40 50 60 MKVLAAGVVP LLLVLHWKHG AGSPLPITPV NATCAIRHPC HNNLMNQIRS QLAQLNGSAN 70 80 90 100 110 120 ALFILYYTAQ GEPFPNNLDK LCGPNVTDFP PFHANGTEKA KLVELYRIVV YLGTSLGNIT 130 140 150 160 170 180 RDQKILNPSA LSLHSKLNAT ADILRGLLSN VLCRLCSKYH VGHVDVTYGP DTSGKDVFQK 190 200 KKLGCQLLGK YKQIIAVLAQ AF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells." Moreau J.-F., Donaldson D.D., Bennett F., Witek-Giannotti J., Clark S.C., Wong G.G. Nature 336:690-692(1988) [PubMed: 3143918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic cloning and heterologous expression of human differentiation-stimulating factor." Lowe D.G., Nunes W., Bombara M., McCabe S., Ranges G.E., Henzel W., Tomida M., Yamamoto-Yamaguchi Y., Hozumi M., Goeddel D.V. DNA 8:351-359(1989) [PubMed: 2475312] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions." Stahl J., Gearing D.P., Willson T.A., Brown M.A., King J.A., Gough N.M. J. Biol. Chem. 265:8833-8841(1990) [PubMed: 1692837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[6]	"Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor." Gough N.M., Gearing D.P., King J.A., Willson T.A., Hilton D.J., Nicola N.A., Metcalf D. Proc. Natl. Acad. Sci. U.S.A. 85:2623-2627(1988) [PubMed: 3128791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-202.
[7]	"Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia." Mori M., Yamaguchi K., Abe K. Biochem. Biophys. Res. Commun. 160:1085-1092(1989) [PubMed: 2730639] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-39.
[8]	"Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor." Schmelzer C.H., Harris R.J., Butler D., Yedinak C.M., Wagner K.L., Burton L.E. Arch. Biochem. Biophys. 302:484-489(1993) [PubMed: 8489250] [Abstract] Cited for: DISULFIDE BONDS, GLYCOSYLATION AT ASN-31; ASN-56; ASN-85; ASN-95; ASN-118 AND ASN-138.
[9]	"Solution structure of leukemia inhibitory factor." Hinds M.G., Maurer T., Zhang J.G., Nicola N.A., Norton R.S. J. Biol. Chem. 273:13738-13745(1998) [PubMed: 9593715] [Abstract] Cited for: STRUCTURE BY NMR OF HUMAN-MOUSE CHIMERA.
[10]	"Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130." Boulanger M.J., Bankovich A.J., Kortemme T., Baker D., Garcia K.C. Mol. Cell 12:577-589(2003) [PubMed: 14527405] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 34-202 IN COMPLEX WITH IL6ST.
[11]	"An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor." Huyton T., Zhang J.G., Luo C.S., Lou M.Z., Hilton D.J., Nicola N.A., Garrett T.P. Proc. Natl. Acad. Sci. U.S.A. 104:12737-12742(2007) [PubMed: 17652170] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 23-202 IN COMPLEX WITH MOUSE LIFR.
+	Additional computationally mapped references.

Web resources

Wikipedia

Leukemia inhibitory factor entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X13967 mRNA. Translation: CAA32147.1.
M27053, M27052 Genomic DNA. Translation: AAA53188.1.
AC004264 Genomic DNA. Translation: AAC05174.1.
M63420 Genomic DNA. Translation: AAA51699.1.
BC069540 mRNA. Translation: AAH69540.1.
BC093733 mRNA. Translation: AAH93733.1.
BC093735 mRNA. Translation: AAH93735.1.
J03261 Genomic DNA. Translation: AAA59517.1.

IPI

IPI00009720.

PIR

B36282.

RefSeq

NP_002300.1.

UniGene

Hs.2250

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A7M	NMR	-	A	-	[»]
1EMR	X-ray	3.50	A	44-202	[»]
1PVH	X-ray	2.50	B/D	34-202	[»]
2Q7N	X-ray	4.00	B/D	23-202	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5769N.

Proteomic databases

PRIDE

P15018.

Genome annotation databases

Ensembl

ENSG00000128342. Homo sapiens. [Contig view]

GeneID

3976.

KEGG

hsa:3976.

Organism-specific databases

GeneCards

GC22M028960.

H-InvDB

HIX0041182.

HGNC

HGNC:6596. LIF.

HPA

HPA018844.

MIM

159540. gene.

PharmGKB

PA30370.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P15018.

HOVERGEN

P15018.

OMA

P15018. LYRIIAY.

Gene expression databases

ArrayExpress

P15018.

Bgee

P15018.

CleanEx

HS_LIF.

GermOnline

ENSG00000128342. Homo sapiens.

Family and domain databases

InterPro

IPR012351. 4_helix_cytokine_core.
IPR003624. Leukemia_IF.
IPR001581. Leukemia_IF/oncostatin.
IPR019827. Leukemia_IF/oncostatin_CS.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

PANTHER

PTHR10633. LIF. 1 hit.

Pfam

PF01291. LIF_OSM. 1 hit.
[Graphical view]

PRINTS

PR01883. LEUKAEMIAIF.

ProDom

PD011266. LIF. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00080. LIF_OSM. 1 hit.
[Graphical view]

PROSITE

PS00590. LIF_OSM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

15584.

PMAP-CutDB

P15018.

SOURCE

Search...

Entry information

Entry name

LIF_HUMAN

Accession

Primary (citable) accession number: P15018
Secondary accession number(s): Q52LZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)