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LIF LIF, interleukin 6 family cytokine [ Homo sapiens (human) ]

Gene ID: 3976, updated on 23-Nov-2017
Official Symbol
LIFprovided by HGNC
Official Full Name
LIF, interleukin 6 family cytokineprovided by HGNC
Primary source
HGNC:HGNC:6596
See related
Ensembl:ENSG00000128342 MIM:159540; Vega:OTTHUMG00000150910
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CDF; DIA; HILDA; MLPLI
Summary
The protein encoded by this gene is a pleiotropic cytokine with roles in several different systems. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the maternal-fetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
Orthologs
Location:
22q12.2
Exon count:
3
Annotation release Status Assembly Chr Location
108 current GRCh38.p7 (GCF_000001405.33) 22 NC_000022.11 (30240447..30246851, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (30636436..30642840, complement)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene HORMA domain containing 2 Neighboring gene ribosomal protein S3a pseudogene 51 Neighboring gene uncharacterized LOC105372988 Neighboring gene uncharacterized LOC91370 Neighboring gene oncostatin M Neighboring gene cytosolic arginine sensor for mTORC1 subunit 1

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Common variants at five new loci associated with early-onset inflammatory bowel disease.
NHGRI GWA Catalog
Genome-wide association study identifies susceptibility loci for IgA nephropathy.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120-treated vaginal epithelial cells show upregulation of leukemia inhibitory factor (LIF) expression as compared to untreated control PubMed
env Pretreatment of MAGI cells with human leukemia inhibitory factor results in a significantly reduced uptake of HIV-1 particles and downregulation of HIV-1 mediated STAT3 phosphorylation PubMed
env HIV-1 gp120 modulates expression of the cytokines IL1beta, IL3, IL6, IL10, IL13, IL15, IFNbeta2A, IFNgamma, IFNomega, TNFalpha, VEGF, VEGF B, and LIF in PBMCs and MDMs PubMed
capsid gag Human LIF protein upregulates HIV-1 p24 production in the chronically infected promonocytes in a dose-dependent manner PubMed

Go to the HIV-1, Human Interaction Database

  • Adipogenesis, organism-specific biosystem (from WikiPathways)
    Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
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  • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
    Direct p53 effectors, organism-specific biosystem
    Direct p53 effectors
  • IL-6-type cytokine receptor ligand interactions, organism-specific biosystem (from REACTOME)
    IL-6-type cytokine receptor ligand interactions, organism-specific biosystemThe members involved in (interleukin)-6-type cytokine signalling are the IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CTF1)...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Interleukin-10 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-10 signaling, organism-specific biosystemInterleukin-10 (IL10) was originally described as a factor named cytokine synthesis inhibitory factor that inhibited T-helper (Th) 1 activation and Th1 cytokine production (Fiorentino et al. 1989). ...
  • Interleukin-4 and 13 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-4 and 13 signaling, organism-specific biosystemInterleukin-4 (IL4) is a principal regulatory cytokine during the immune response, crucially important in allergy and asthma (Nelms et al. 1999). When resting T cells are antigen-activated and expand...
  • Interleukin-6 family signaling, organism-specific biosystem (from REACTOME)
    Interleukin-6 family signaling, organism-specific biosystemThe interleukin (IL)-6 family of cytokines is defined by the shared use of the common signal transducing receptor gp130 beta-subunit. This family includes structurally and functionally related IL-6, ...
  • Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
    Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
  • Jak-STAT signaling pathway, conserved biosystem (from KEGG)
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  • MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
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  • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
    Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
  • Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
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  • TGF-beta Receptor Signaling, organism-specific biosystem (from WikiPathways)
    TGF-beta Receptor Signaling, organism-specific biosystemThe Transforming growth factor beta (TGFβ) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiat...
  • TNF signaling pathway, organism-specific biosystem (from KEGG)
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  • Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem (from Pathway Interaction Database)
    Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem
    Validated transcriptional targets of AP1 family members Fra1 and Fra2
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cytokine activity IDA
Inferred from Direct Assay
more info
PubMed 
growth factor activity IDA
Inferred from Direct Assay
more info
PubMed 
leukemia inhibitory factor receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
leukemia inhibitory factor receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
blood vessel remodeling IEA
Inferred from Electronic Annotation
more info
 
decidualization IEA
Inferred from Electronic Annotation
more info
 
embryo implantation IEA
Inferred from Electronic Annotation
more info
 
immune response IEA
Inferred from Electronic Annotation
more info
 
leukemia inhibitory factor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
lung alveolus development IEA
Inferred from Electronic Annotation
more info
 
lung lobe morphogenesis IEA
Inferred from Electronic Annotation
more info
 
lung vasculature development IEA
Inferred from Electronic Annotation
more info
 
multicellular organism development TAS
Traceable Author Statement
more info
PubMed 
muscle organ morphogenesis IEA
Inferred from Electronic Annotation
more info
 
negative regulation of ERK1 and ERK2 cascade IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of hormone secretion IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of meiotic nuclear division IEA
Inferred from Electronic Annotation
more info
 
neuron development IEA
Inferred from Electronic Annotation
more info
 
positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of astrocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of histone H3-K27 acetylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of macrophage differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of peptidyl-serine phosphorylation of STAT protein IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein localization to nucleus IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of tyrosine phosphorylation of STAT protein IDA
Inferred from Direct Assay
more info
PubMed 
regulation of RNA polymerase II regulatory region sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
 
regulation of metanephric nephron tubule epithelial cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of receptor activity IEA
Inferred from Electronic Annotation
more info
 
spongiotrophoblast differentiation IEA
Inferred from Electronic Annotation
more info
 
stem cell differentiation IEA
Inferred from Electronic Annotation
more info
 
stem cell population maintenance IEA
Inferred from Electronic Annotation
more info
 
trophoblast giant cell differentiation IEA
Inferred from Electronic Annotation
more info
 
tyrosine phosphorylation of STAT protein IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol IDA
Inferred from Direct Assay
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IC
Inferred by Curator
more info
PubMed 
Preferred Names
leukemia inhibitory factor
Names
D factor
cholinergic differentiation factor
differentiation inhibitory activity
differentiation-inducing factor
differentiation-stimulating factor
hepatocyte-stimulating factor III
human interleukin in DA cells
melanoma-derived LPL inhibitor

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008721.1 RefSeqGene

    Range
    4957..11361
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001257135.1NP_001244064.1  leukemia inhibitory factor isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC004264, AI796373, BC143305, CN409458
    Consensus CDS
    CCDS58799.1
    UniProtKB/Swiss-Prot
    P15018
    Related
    ENSP00000384450.3, OTTHUMP00000198699, ENST00000403987.3, OTTHUMT00000320509
  2. NM_002309.4NP_002300.1  leukemia inhibitory factor isoform 1 precursor

    See identical proteins and their annotated locations for NP_002300.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC004264, AI796373, CN409458
    Consensus CDS
    CCDS13872.1
    UniProtKB/Swiss-Prot
    P15018
    Related
    ENSP00000249075.3, OTTHUMP00000198698, ENST00000249075.3, OTTHUMT00000320508
    Conserved Domains (1) summary
    smart00080
    Location:34191
    LIF_OSM; leukemia inhibitory factor

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p7 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p7 Primary Assembly

    Range
    30240447..30246851 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018933.2 Alternate CHM1_1.1

    Range
    30595573..30601977 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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