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

Summary

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
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]
Expression: Broad expression in gall bladder (RPKM 20.9), appendix (RPKM 11.6) and 16 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 22q12.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	22	NC_000022.11 (30240447..30257487, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (30636436..30642840, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Ruxolitinib-treated tumors in both the immunocompromised and immunocompetent animal models demonstrate decreased phospho-STAT3, indicating on-target activity. In conclusion, CA-MSC activate ovarian cancer cell STAT3 signaling via IL6 and LIF and increase tumor cell stemness.
Title: Leukemia inhibitory factor functions in parallel with interleukin-6 to promote ovarian cancer growth.
In serum from human PDAC patients, authors found that LIF titers positively correlated with intratumoral nerve density.
Title: LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker.
miR-181c-3p and -5p promotes high-glucose-induced dysfunction in human umbilical vein endothelial cells by regulating leukemia inhibitory factor
Title: miR-181c-3p and -5p promotes high-glucose-induced dysfunction in human umbilical vein endothelial cells by regulating leukemia inhibitory factor.
The findings indicate that low LIF concentrations in serum and follicular fluid may contribute to disordered folliculogenesis in polycystic ovary syndrome.
Title: Leukaemia inhibitory factor in serum and follicular fluid of women with polycystic ovary syndrome and its correlation with IVF outcome.
This study uses LIF to activate the PI3K/ AKT signal and induce the anti-inflammatory effect during the neuron differentiation from human induced pluripotent stem cell-derived neural precursor cells.
Title: Effect of leukocyte inhibitory factor on neuron differentiation from human induced pluripotent stem cell-derived neural precursor cells.
These findings implicate ZEB1 as a stem cell regulator in glioma via LIF repression which when deleted leads to increased stemness, tumorigenicity and shortened patient survival.
Title: ZEB1 regulates glioma stemness through LIF repression.
Decreased serum LIF levels may be associated with vasculopathy in systemic sclerosis (SSc) and that Fli1 deficiency may contribute to the inhibition of LIF-dependent biological effects on SSc endothelial cells by suppressing the expression of LIF, LIF receptor, and gp130.
Title: A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis.
The endometrial expression of LIF and CD34 in the pathogenesis of non-developing pregnancy can be used for evaluating the pregnancy prognosis in women of young and old reproductive age.
Title: Role of LIF Cytokine and CD34 Angiogenesis Marker in Non-Developing Pregnancy.
This report describes the involvement of proteins responsible for cell growth and progression and defines the LIF-mediated novel autocrine-paracrine signaling loop for cell growth arrest.
Title: Examination of pathways involved in leukemia inhibitory factor (LIF)-induced cell growth arrest using label-free proteomics approach.
The expression of LIF was associated with tumor size and a poorer overall survival. Microarray and quantitative real-time polymerase chain reaction assessments suggest that LIF can facilitate tumor-promoting inflammation. Results indicate that LIF plays a role in maintaining cancer stem cells in chordomas.
Title: Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma.

Submit: New GeneRIF Correction See all GeneRIFs (154)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Pathways from BioSystems

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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)
Cytokine-cytokine receptor interaction, conserved 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 ...
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)
Jak-STAT signaling pathway, conserved 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...
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
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)
Signaling pathways regulating pluripotency of stem cells, conserved 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...
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)
TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
TNF signaling pathway, conserved biosystem (from KEGG)
TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:481059

NoName (e-PCR)
- UniSTS:483713

RH27829 (e-PCR)
- UniSTS:90754

GDB:624823 (e-PCR)
- UniSTS:158363

GDB:625815 (e-PCR)
- UniSTS:158366

SHGC-145300 (e-PCR)
- UniSTS:174504

SHGC-7772 (e-PCR)
- UniSTS:44530

Homology

Homologs of the LIF gene: The LIF gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Orthologs from Annotation Pipeline: 187 organisms have orthologs with human gene LIF
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytokine activity	IDA Inferred from Direct Assay more info	PubMed
growth factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
growth factor activity	IDA Inferred from Direct Assay more info	PubMed
leukemia inhibitory factor receptor binding	IBA Inferred from Biological aspect of Ancestor 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
signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
blood vessel remodeling	IEA Inferred from Electronic Annotation more info
cytokine-mediated signaling pathway	TAS Traceable Author Statement 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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 by RNA polymerase II	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 cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of metanephric nephron tubule epithelial cell differentiation	IDA Inferred from Direct Assay more info	PubMed
regulation of signaling 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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	IC Inferred by Curator more info	PubMed

General protein information

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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

NCBI Reference Sequences (RefSeq)

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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

NG_008721.1 RefSeqGene

Range

4957..11361

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001257135.1 → NP_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, ENST00000403987.3
NM_002309.5 → NP_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, ENST00000249075.4

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p12 Primary Assembly

Range

30240447..30257487 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024452239.1 → XP_024308007.1 leukemia inhibitory factor isoform X1

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor
XM_024452240.1 → XP_024308008.1 leukemia inhibitory factor isoform X1

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor