P15018 (LIF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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 Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological process	immune response Inferred from electronic annotation. Source: InterPro leukemia inhibitory factor signaling pathway Inferred from direct assay. Source: BHF-UCL 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 Inferred from direct assay. Source: BHF-UCL positive regulation of macrophage differentiation Inferred from direct assay. Source: MGI positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis Inferred from direct assay. Source: BHF-UCL positive regulation of peptidyl-serine phosphorylation of STAT protein Inferred from direct assay. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from direct assay. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay. Source: BHF-UCL regulation of metanephric nephron tubule epithelial cell differentiation Inferred from direct assay. Source: BHF-UCL
Cellular component	extracellular space Inferred by curator. Source: BHF-UCL
Molecular function	cytokine activity Inferred from direct assay. Source: MGI growth factor activity Inferred from direct assay. Source: BHF-UCL leukemia inhibitory factor receptor binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.9

Chain

23 – 202

180

Leukemia inhibitory factor

PRO_0000017715

Amino acid modifications

Glycosylation

31

1

N-linked (GlcNAc...) Ref.10

Glycosylation

56

1

N-linked (GlcNAc...) Ref.10

Glycosylation

85

1

N-linked (GlcNAc...) Ref.10

Glycosylation

95

1

N-linked (GlcNAc...) Ref.10

Glycosylation

118

1

N-linked (GlcNAc...) Ref.10

Glycosylation

138

1

N-linked (GlcNAc...) Ref.10

Disulfide bond

34 ↔ 156

Ref.10

Disulfide bond

40 ↔ 153

Ref.10

Disulfide bond

82 ↔ 185

Ref.10

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 [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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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

EMBL
GenBank
DDBJ

X13967 mRNA. Translation: CAA32147.1.
M27053, M27052 Genomic DNA. Translation: AAA53188.1.
AC004264 Genomic DNA. Translation: AAC05174.1.
M63420 Genomic DNA. Translation: AAA51699.1.
AK315310 mRNA. Translation: BAG37714.1.
CH471095 Genomic DNA. Translation: EAW59863.1.
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. NM_002309.3.

UniGene

Hs.2250.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
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	[»]

ProteinModelPortal

P15018.

SMR

P15018. Positions 23-202.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5769N.

IntAct

P15018. 1 interaction.

MINT

MINT-1352030.

STRING

P15018.

Polymorphism databases

DMDM

126279.

Proteomic databases

PRIDE

P15018.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000249075; ENSP00000249075; ENSG00000128342.

GeneID

3976.

KEGG

hsa:3976.

UCSC

uc003agz.1. human.

Organism-specific databases

CTD

3976.

GeneCards

GC22M030636.

H-InvDB

HIX0041182.

HGNC

HGNC:6596. LIF.

HPA

CAB025985.
HPA018844.

MIM

159540. gene.

neXtProt

NX_P15018.

PharmGKB

PA30370.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07733.

GeneTree

ENSGT00390000000059.

HOGENOM

HBG125109.

HOVERGEN

HBG006267.

InParanoid

P15018.

OMA

KYHVAHV.

OrthoDB

EOG4RXZ18.

PhylomeDB

P15018.

Gene expression databases

ArrayExpress

P15018.

Bgee

P15018.

CleanEx

HS_LIF.

Genevestigator

P15018.

GermOnline

ENSG00000128342. Homo sapiens.

Family and domain databases

InterPro

IPR009079. 4_helix_cytokine-like_core.
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.

KO

K05419.

PANTHER

PTHR10633. LIF. 1 hit.

Pfam

PF01291. LIF_OSM. 1 hit.
[Graphical view]

PRINTS

PR01883. LEUKAEMIAIF.

SMART

SM00080. LIF_OSM. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00590. LIF_OSM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

15584.

PMAP-CutDB

P15018.

SOURCE

Search...

Entry information

Entry name

LIF_HUMAN

Accession

Primary (citable) accession number: P15018
Secondary accession number(s): B2RCW7, Q52LZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	January 25, 2012
This is version 127 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.