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Protein

Leukemia inhibitory factor

Gene

Lif

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • cytokine activity Source: MGI
  • growth factor activity Source: MGI
  • leukemia inhibitory factor receptor binding Source: MGI
  • receptor binding Source: MGI
  • transcription factor activity, RNA polymerase II transcription factor recruiting Source: MGI

GO - Biological processi

  • astrocyte differentiation Source: Ensembl
  • blood vessel remodeling Source: MGI
  • decidualization Source: MGI
  • embryo implantation Source: MGI
  • immune response Source: InterPro
  • leukemia inhibitory factor signaling pathway Source: MGI
  • lung alveolus development Source: MGI
  • lung development Source: MGI
  • lung lobe morphogenesis Source: MGI
  • lung vasculature development Source: MGI
  • maternal process involved in female pregnancy Source: MGI
  • muscle organ morphogenesis Source: MGI
  • negative regulation of angiogenesis Source: Ensembl
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of ERK1 and ERK2 cascade Source: MGI
  • negative regulation of hormone secretion Source: MGI
  • negative regulation of meiotic nuclear division Source: MGI
  • neuron development Source: MGI
  • organ regeneration Source: Ensembl
  • positive regulation of astrocyte differentiation Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of corticotropin secretion Source: Ensembl
  • positive regulation of gene expression Source: MGI
  • positive regulation of histone H3-K27 acetylation Source: MGI
  • positive regulation of macrophage differentiation Source: MGI
  • positive regulation of MAPK cascade Source: MGI
  • positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis Source: MGI
  • positive regulation of neuron projection development Source: Ensembl
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of peptidyl-serine phosphorylation of STAT protein Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of protein localization to nucleus Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of tyrosine phosphorylation of Stat1 protein Source: MGI
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: MGI
  • regulation of cell differentiation Source: MGI
  • regulation of metanephric nephron tubule epithelial cell differentiation Source: MGI
  • regulation of RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • retina development in camera-type eye Source: Ensembl
  • spongiotrophoblast differentiation Source: MGI
  • stem cell differentiation Source: MGI
  • stem cell population maintenance Source: MGI
  • transdifferentiation Source: Ensembl
  • trophoblast giant cell differentiation Source: MGI
  • tyrosine phosphorylation of Stat3 protein Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

ReactomeiR-MMU-6788467. IL-6-type cytokine receptor ligand interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukemia inhibitory factor
Short name:
LIF
Alternative name(s):
Differentiation-stimulating factor
Short name:
D factor
Gene namesi
Name:Lif
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:96787. Lif.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23231 PublicationAdd
BLAST
Chaini24 – 203180Leukemia inhibitory factorPRO_0000017716Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi32 – 321N-linked (GlcNAc...)
Disulfide bondi35 ↔ 1571 Publication
Disulfide bondi41 ↔ 1541 Publication
Glycosylationi57 – 571N-linked (GlcNAc...)
Disulfide bondi83 ↔ 1861 Publication
Glycosylationi86 – 861N-linked (GlcNAc...)Sequence analysis
Glycosylationi96 – 961N-linked (GlcNAc...)Sequence analysis
Glycosylationi119 – 1191N-linked (GlcNAc...)
Glycosylationi139 – 1391N-linked (GlcNAc...)

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP09056.
PaxDbiP09056.
PRIDEiP09056.

Expressioni

Gene expression databases

BgeeiP09056.
CleanExiMM_LIF.
ExpressionAtlasiP09056. baseline and differential.
GenevisibleiP09056. MM.

Interactioni

GO - Molecular functioni

  • cytokine activity Source: MGI
  • growth factor activity Source: MGI
  • leukemia inhibitory factor receptor binding Source: MGI
  • receptor binding Source: MGI

Protein-protein interaction databases

DIPiDIP-5771N.
STRINGi10090.ENSMUSP00000067066.

Structurei

Secondary structure

1
203
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi32 – 343Combined sources
Helixi35 – 373Combined sources
Helixi45 – 7127Combined sources
Beta strandi73 – 753Combined sources
Helixi76 – 783Combined sources
Helixi79 – 824Combined sources
Helixi99 – 12729Combined sources
Helixi132 – 15827Combined sources
Helixi178 – 20023Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A7MNMR-A24-203[»]
1LKIX-ray2.00A24-203[»]
ProteinModelPortaliP09056.
SMRiP09056. Positions 32-203.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09056.

Family & Domainsi

Sequence similaritiesi

Belongs to the LIF/OSM family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410ITBQ. Eukaryota.
ENOG410YVPP. LUCA.
GeneTreeiENSGT00390000000059.
HOGENOMiHOG000059647.
HOVERGENiHBG006267.
InParanoidiP09056.
KOiK05419.
OMAiKYHVAHV.
OrthoDBiEOG7JX359.
PhylomeDBiP09056.
TreeFamiTF336245.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003624. Leukemia_IF.
IPR001581. Leukemia_IF/oncostatin.
IPR019827. Leukemia_IF/oncostatin_CS.
[Graphical view]
PANTHERiPTHR10633. PTHR10633. 1 hit.
PfamiPF01291. LIF_OSM. 1 hit.
[Graphical view]
PRINTSiPR01883. LEUKAEMIAIF.
SMARTiSM00080. LIF_OSM. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00590. LIF_OSM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09056-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVLAAGIVP LLLLVLHWKH GAGSPLPITP VNATCAIRHP CHGNLMNQIK
60 70 80 90 100
NQLAQLNGSA NALFISYYTA QGEPFPNNVE KLCAPNMTDF PSFHGNGTEK
110 120 130 140 150
TKLVELYRMV AYLSASLTNI TRDQKVLNPT AVSLQVKLNA TIDVMRGLLS
160 170 180 190 200
NVLCRLCNKY RVGHVDVPPV PDHSDKEAFQ RKKLGCQLLG TYKQVISVVV

QAF
Length:203
Mass (Da):22,287
Last modified:November 1, 1988 - v1
Checksum:iF5C65EF11A67A835
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12810 mRNA. Translation: CAA31299.1.
X06381 mRNA. Translation: CAA29680.1.
AF065917 mRNA. Translation: AAC17912.1.
AF065918 mRNA. Translation: AAC17913.1.
M63419 Genomic DNA. Translation: AAA37211.1.
M57691 mRNA. Translation: AAA63388.1.
CCDSiCCDS24383.1.
PIRiA36282.
RefSeqiNP_001034626.1. NM_001039537.2.
NP_032527.1. NM_008501.2.
XP_006514605.1. XM_006514542.2.
XP_006514606.1. XM_006514543.2.
UniGeneiMm.4964.

Genome annotation databases

EnsembliENSMUST00000066283; ENSMUSP00000067066; ENSMUSG00000034394.
GeneIDi16878.
KEGGimmu:16878.
UCSCiuc007hut.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12810 mRNA. Translation: CAA31299.1.
X06381 mRNA. Translation: CAA29680.1.
AF065917 mRNA. Translation: AAC17912.1.
AF065918 mRNA. Translation: AAC17913.1.
M63419 Genomic DNA. Translation: AAA37211.1.
M57691 mRNA. Translation: AAA63388.1.
CCDSiCCDS24383.1.
PIRiA36282.
RefSeqiNP_001034626.1. NM_001039537.2.
NP_032527.1. NM_008501.2.
XP_006514605.1. XM_006514542.2.
XP_006514606.1. XM_006514543.2.
UniGeneiMm.4964.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A7MNMR-A24-203[»]
1LKIX-ray2.00A24-203[»]
ProteinModelPortaliP09056.
SMRiP09056. Positions 32-203.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-5771N.
STRINGi10090.ENSMUSP00000067066.

Proteomic databases

EPDiP09056.
PaxDbiP09056.
PRIDEiP09056.

Protocols and materials databases

DNASUi16878.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000066283; ENSMUSP00000067066; ENSMUSG00000034394.
GeneIDi16878.
KEGGimmu:16878.
UCSCiuc007hut.1. mouse.

Organism-specific databases

CTDi3976.
MGIiMGI:96787. Lif.

Phylogenomic databases

eggNOGiENOG410ITBQ. Eukaryota.
ENOG410YVPP. LUCA.
GeneTreeiENSGT00390000000059.
HOGENOMiHOG000059647.
HOVERGENiHBG006267.
InParanoidiP09056.
KOiK05419.
OMAiKYHVAHV.
OrthoDBiEOG7JX359.
PhylomeDBiP09056.
TreeFamiTF336245.

Enzyme and pathway databases

ReactomeiR-MMU-6788467. IL-6-type cytokine receptor ligand interactions.

Miscellaneous databases

EvolutionaryTraceiP09056.
NextBioi290872.
PROiP09056.
SOURCEiSearch...

Gene expression databases

BgeeiP09056.
CleanExiMM_LIF.
ExpressionAtlasiP09056. baseline and differential.
GenevisibleiP09056. MM.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003624. Leukemia_IF.
IPR001581. Leukemia_IF/oncostatin.
IPR019827. Leukemia_IF/oncostatin_CS.
[Graphical view]
PANTHERiPTHR10633. PTHR10633. 1 hit.
PfamiPF01291. LIF_OSM. 1 hit.
[Graphical view]
PRINTSiPR01883. LEUKAEMIAIF.
SMARTiSM00080. LIF_OSM. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00590. LIF_OSM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Complete sequence of murine myeloid leukaemia inhibitory factor (LIF)."
    Gough N.M., Gearing D.P., King J.A.
    Nucleic Acids Res. 16:9857-9857(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis."
    Teuscher C., Butterfield R.J., Ma R.Z., Zachary J.F., Doerge R.W., Blankenhorn E.P.
    J. Immunol. 163:2262-2266(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE.
    Strain: B10.S/J and SJL/J.
    Tissue: Spleen.
  4. "Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF)."
    Gearing D.P., Gough N.M., King J.A., Hilton D.J., Nicola N.A., Simpson R.J., Nice E.C., Kelso A., Metcalf D.
    EMBO J. 6:3995-4002(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-203, PROTEIN SEQUENCE OF 195-203.
  5. "Biochemical characterization of murine leukaemia inhibitory factor produced by Krebs ascites and by yeast cells."
    Gough N.M., Hilton D.J., Gearing D.P., Willson T.A., King J.A., Nicola N.A., Metcalf D.
    Blood Cells 14:431-442(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 178-203.
  6. "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] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 24-81 AND 108-176.
  7. "The disulfide bond arrangement of leukemia inhibitory factor: homology to oncostatin M and structural implications."
    Nicola N.A., Cross B., Simpson R.J.
    Biochem. Biophys. Res. Commun. 190:20-26(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  8. "The crystal structure and biological function of leukemia inhibitory factor: implications for receptor binding."
    Robinson R.C., Grey L.M., Staunton D., Vankelecom H., Vernallis A.B., Moreau J.-F., Stuart D.I., Heath J.K., Jones E.Y.
    Cell 77:1101-1116(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
  9. "Solution dynamics and secondary structure of murine leukemia inhibitory factor: a four-helix cytokine with a rigid CD loop."
    Purvis D.H., Mabbutt B.C.
    Biochemistry 36:10146-10154(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  10. Cited for: STRUCTURE BY NMR OF HUMAN-MOUSE CHIMERA.

Entry informationi

Entry nameiLIF_MOUSE
AccessioniPrimary (citable) accession number: P09056
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: March 16, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.