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
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	22	NC_000022.11 (30240453..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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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 Functions

What's a GeneRIF?

Study shows that LIF expression is induced specifically by oncogenic KRAS in pancreatic ductal adenocarcinomas (PDAC) and that LIF depletion by genetic means or by neutralizing antibodies prevents engraftment in pancreatic xenograft models. The related cytokine IL-6 cannot substitute for LIF, suggesting that LIF mediates KRAS-driven malignancies through a non-STAT-signaling pathway.
Title: Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer.
Interplay Between Helicobacter pylori Infection, Interleukin-11, and Leukemia Inhibitory Factor in Gastric Cancer Among Egyptian Patients
Title: Interplay Between Helicobacter pylori Infection, Interleukin-11, and Leukemia Inhibitory Factor in Gastric Cancer Among Egyptian Patients.
findings reveal a function of LIF in pancreatic ductal adenocarcinoma tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker; studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy
Title: Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.
Differential expression of LIF and IGF-1 in molar trophoblasts and chorionic villi might have a role in regulation of trophoblasts in complete moles. Decreased expression of glandular IGF-1 and decidual LIF might be related to the decidual changes during trophoblastic proliferation and invasion of decidua in complete HMs.
Title: Differential expression of leukemia inhibitory factor and insulin like growth factor-1 between normal pregnancies, partial hydatidiform moles and complete hydatidiform moles.
The association between ESR1 and LIF polymorphisms can help in the prediction of recurrent implantation failure.
Title: Association between estrogen receptor 1 (ESR1) and leukemia inhibitory factor (LIF) polymorphisms can help in the prediction of recurrent implantation failure.
Although rhLIF had no effect on proliferation, it inhibited apoptosis of degenerated nucleus pulposus cells in a concentrationdependent manner. LIF was upregulated during the process of intervertebral disc degeneration, and may promote the expression of extracellular matrix components.
Title: Expression and effects of leukemia inhibitory factor on nucleus pulposus degeneration.
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.

Submit: New GeneRIF Correction See all GeneRIFs (159)

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

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: 201 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
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

5049..11355

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001257135.2 → 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 Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p13 Primary Assembly

Range

30240453..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