LIF_MOUSE
ID LIF_MOUSE Reviewed; 203 AA.
AC P09056;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Leukemia inhibitory factor;
DE Short=LIF;
DE AltName: Full=Differentiation-stimulating factor;
DE Short=D factor;
DE Flags: Precursor;
GN Name=Lif;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3186448; DOI=10.1093/nar/16.20.9857;
RA Gough N.M., Gearing D.P., King J.A.;
RT "Complete sequence of murine myeloid leukaemia inhibitory factor (LIF).";
RL Nucleic Acids Res. 16:9857-9857(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1692837; DOI=10.1016/s0021-9258(19)38963-x;
RA Stahl J., Gearing D.P., Willson T.A., Brown M.A., King J.A., Gough N.M.;
RT "Structural organization of the genes for murine and human leukemia
RT inhibitory factor. Evolutionary conservation of coding and non-coding
RT regions.";
RL J. Biol. Chem. 265:8833-8841(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=B10.S/J, and SJL/J; TISSUE=Spleen;
RX PubMed=10438970;
RA Teuscher C., Butterfield R.J., Ma R.Z., Zachary J.F., Doerge R.W.,
RA Blankenhorn E.P.;
RT "Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte
RT chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for
RT eae7, a locus controlling susceptibility to monophasic
RT remitting/nonrelapsing experimental allergic encephalomyelitis.";
RL J. Immunol. 163:2262-2266(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-203, AND PROTEIN SEQUENCE OF 195-203.
RX PubMed=3127201; DOI=10.1002/j.1460-2075.1987.tb02742.x;
RA Gearing D.P., Gough N.M., King J.A., Hilton D.J., Nicola N.A.,
RA Simpson R.J., Nice E.C., Kelso A., Metcalf D.;
RT "Molecular cloning and expression of cDNA encoding a murine myeloid
RT leukaemia inhibitory factor (LIF).";
RL EMBO J. 6:3995-4002(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 178-203.
RX PubMed=3147726;
RA Gough N.M., Hilton D.J., Gearing D.P., Willson T.A., King J.A.,
RA Nicola N.A., Metcalf D.;
RT "Biochemical characterization of murine leukaemia inhibitory factor
RT produced by Krebs ascites and by yeast cells.";
RL Blood Cells 14:431-442(1988).
RN [6]
RP PROTEIN SEQUENCE OF 24-81 AND 108-176.
RX PubMed=2475312; DOI=10.1089/dna.1.1989.8.351;
RA Lowe D.G., Nunes W., Bombara M., McCabe S., Ranges G.E., Henzel W.,
RA Tomida M., Yamamoto-Yamaguchi Y., Hozumi M., Goeddel D.V.;
RT "Genomic cloning and heterologous expression of human differentiation-
RT stimulating factor.";
RL DNA 8:351-359(1989).
RN [7]
RP DISULFIDE BONDS.
RX PubMed=8422244; DOI=10.1006/bbrc.1993.1004;
RA Nicola N.A., Cross B., Simpson R.J.;
RT "The disulfide bond arrangement of leukemia inhibitory factor: homology to
RT oncostatin M and structural implications.";
RL Biochem. Biophys. Res. Commun. 190:20-26(1993).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=8020098; DOI=10.1016/0092-8674(94)90449-9;
RA Robinson R.C., Grey L.M., Staunton D., Vankelecom H., Vernallis A.B.,
RA Moreau J.-F., Stuart D.I., Heath J.K., Jones E.Y.;
RT "The crystal structure and biological function of leukemia inhibitory
RT factor: implications for receptor binding.";
RL Cell 77:1101-1116(1994).
RN [9]
RP STRUCTURE BY NMR.
RX PubMed=9254611; DOI=10.1021/bi970665m;
RA Purvis D.H., Mabbutt B.C.;
RT "Solution dynamics and secondary structure of murine leukemia inhibitory
RT factor: a four-helix cytokine with a rigid CD loop.";
RL Biochemistry 36:10146-10154(1997).
RN [10]
RP STRUCTURE BY NMR OF HUMAN-MOUSE CHIMERA.
RX PubMed=9593715; DOI=10.1074/jbc.273.22.13738;
RA Hinds M.G., Maurer T., Zhang J.G., Nicola N.A., Norton R.S.;
RT "Solution structure of leukemia inhibitory factor.";
RL J. Biol. Chem. 273:13738-13745(1998).
CC -!- FUNCTION: LIF has the capacity to induce terminal differentiation in
CC leukemic cells. Its activities include the induction of hematopoietic
CC differentiation in normal and myeloid leukemia cells, the induction of
CC neuronal cell differentiation, and the stimulation of acute-phase
CC protein synthesis in hepatocytes.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the LIF/OSM family. {ECO:0000305}.
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DR EMBL; X12810; CAA31299.1; -; mRNA.
DR EMBL; X06381; CAA29680.1; -; mRNA.
DR EMBL; AF065917; AAC17912.1; -; mRNA.
DR EMBL; AF065918; AAC17913.1; -; mRNA.
DR EMBL; M63419; AAA37211.1; -; Genomic_DNA.
DR EMBL; M57691; AAA63388.1; -; mRNA.
DR CCDS; CCDS24383.1; -.
DR PIR; A36282; A36282.
DR RefSeq; NP_001034626.1; NM_001039537.2.
DR RefSeq; NP_032527.1; NM_008501.2.
DR RefSeq; XP_006514605.1; XM_006514542.3.
DR RefSeq; XP_006514606.1; XM_006514543.3.
DR PDB; 1A7M; NMR; -; A=24-203.
DR PDB; 1LKI; X-ray; 2.00 A; A=24-203.
DR PDBsum; 1A7M; -.
DR PDBsum; 1LKI; -.
DR AlphaFoldDB; P09056; -.
DR SMR; P09056; -.
DR DIP; DIP-5771N; -.
DR STRING; 10090.ENSMUSP00000067066; -.
DR GlyGen; P09056; 6 sites.
DR EPD; P09056; -.
DR PaxDb; P09056; -.
DR PRIDE; P09056; -.
DR ProteomicsDB; 264983; -.
DR Antibodypedia; 10647; 593 antibodies from 45 providers.
DR DNASU; 16878; -.
DR Ensembl; ENSMUST00000066283; ENSMUSP00000067066; ENSMUSG00000034394.
DR GeneID; 16878; -.
DR KEGG; mmu:16878; -.
DR UCSC; uc007hut.1; mouse.
DR CTD; 3976; -.
DR MGI; MGI:96787; Lif.
DR VEuPathDB; HostDB:ENSMUSG00000034394; -.
DR eggNOG; ENOG502S3JD; Eukaryota.
DR GeneTree; ENSGT00390000000059; -.
DR HOGENOM; CLU_117011_0_0_1; -.
DR InParanoid; P09056; -.
DR OMA; DVSYGPD; -.
DR OrthoDB; 1240691at2759; -.
DR PhylomeDB; P09056; -.
DR TreeFam; TF336245; -.
DR Reactome; R-MMU-6788467; IL-6-type cytokine receptor ligand interactions.
DR BioGRID-ORCS; 16878; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Lifr; mouse.
DR EvolutionaryTrace; P09056; -.
DR PRO; PR:P09056; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P09056; protein.
DR Bgee; ENSMUSG00000034394; Expressed in endometrium and 46 other tissues.
DR ExpressionAtlas; P09056; baseline and differential.
DR Genevisible; P09056; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; IMP:MGI.
DR GO; GO:0005146; F:leukemia inhibitory factor receptor binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0031100; P:animal organ regeneration; ISO:MGI.
DR GO; GO:0048708; P:astrocyte differentiation; ISO:MGI.
DR GO; GO:0001974; P:blood vessel remodeling; IGI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0046697; P:decidualization; IDA:MGI.
DR GO; GO:0007566; P:embryo implantation; IDA:MGI.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0048861; P:leukemia inhibitory factor signaling pathway; ISO:MGI.
DR GO; GO:0048286; P:lung alveolus development; IGI:MGI.
DR GO; GO:0030324; P:lung development; IGI:MGI.
DR GO; GO:0060463; P:lung lobe morphogenesis; IGI:MGI.
DR GO; GO:0060426; P:lung vasculature development; IGI:MGI.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IMP:MGI.
DR GO; GO:0140013; P:meiotic nuclear division; IDA:MGI.
DR GO; GO:0048644; P:muscle organ morphogenesis; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IGI:MGI.
DR GO; GO:0046888; P:negative regulation of hormone secretion; ISO:MGI.
DR GO; GO:0045835; P:negative regulation of meiotic nuclear division; IDA:MGI.
DR GO; GO:0048666; P:neuron development; IGI:MGI.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; IDA:MGI.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051461; P:positive regulation of corticotropin secretion; ISO:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:MGI.
DR GO; GO:1901676; P:positive regulation of histone H3-K27 acetylation; ISO:MGI.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0072108; P:positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0045595; P:regulation of cell differentiation; IGI:MGI.
DR GO; GO:0072307; P:regulation of metanephric nephron tubule epithelial cell differentiation; ISO:MGI.
DR GO; GO:1903025; P:regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0060041; P:retina development in camera-type eye; ISO:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:MGI.
DR GO; GO:0060708; P:spongiotrophoblast differentiation; IGI:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
DR GO; GO:0060290; P:transdifferentiation; ISO:MGI.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IGI:MGI.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:MGI.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR003624; Leukemia_IF.
DR InterPro; IPR001581; Leukemia_IF/oncostatin.
DR InterPro; IPR019827; Leukemia_IF/oncostatin_CS.
DR PANTHER; PTHR10633; PTHR10633; 1.
DR Pfam; PF01291; LIF_OSM; 1.
DR PRINTS; PR01883; LEUKAEMIAIF.
DR SMART; SM00080; LIF_OSM; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00590; LIF_OSM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytokine; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:2475312"
FT CHAIN 24..203
FT /note="Leukemia inhibitory factor"
FT /id="PRO_0000017716"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 35..157
FT /evidence="ECO:0000269|PubMed:8422244"
FT DISULFID 41..154
FT /evidence="ECO:0000269|PubMed:8422244"
FT DISULFID 83..186
FT /evidence="ECO:0000269|PubMed:8422244"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:1A7M"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:1LKI"
FT HELIX 45..71
FT /evidence="ECO:0007829|PDB:1LKI"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:1A7M"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1LKI"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:1LKI"
FT HELIX 99..127
FT /evidence="ECO:0007829|PDB:1LKI"
FT HELIX 132..158
FT /evidence="ECO:0007829|PDB:1LKI"
FT HELIX 178..200
FT /evidence="ECO:0007829|PDB:1LKI"
SQ SEQUENCE 203 AA; 22287 MW; F5C65EF11A67A835 CRC64;
MKVLAAGIVP LLLLVLHWKH GAGSPLPITP VNATCAIRHP CHGNLMNQIK NQLAQLNGSA
NALFISYYTA QGEPFPNNVE KLCAPNMTDF PSFHGNGTEK TKLVELYRMV AYLSASLTNI
TRDQKVLNPT AVSLQVKLNA TIDVMRGLLS NVLCRLCNKY RVGHVDVPPV PDHSDKEAFQ
RKKLGCQLLG TYKQVISVVV QAF
