InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: HIF1A

Summary

InnateDB Gene

IDBG-8510.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HIF1A

Gene Name

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

Synonyms

bHLHe78; HIF-1A; HIF-1alpha; HIF1; HIF1-ALPHA; MOP1; PASD8

Species

Homo sapiens

Ensembl Gene

ENSG00000100644

Encoded Proteins

IDBP-8512

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

IDBP-8514

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

IDBP-240420

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

IDBP-597840

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

IDBP-583325

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 18606657

HIF1A transcription is induced by IFNA2 in human endothelial cells though a JAK-ISGF3 pathway under normoxic conditions, and that this response contributes to the anti-proliferative activity of this cytokine.

PMID 17965024

HIF1A expression is regulated by intracellular calcium levels, resulting in modulation of PPP3CA (calcineurin) activity and RACK1 dimerization.

PMID 20517715

Hypoxia-inducible factors (HIFs), including HIF1A, regulate glycolytic energy generation, optimize innate immunity, control pro-inflammatory gene expression, mediate bacterial killing and influence cell migration. HIFs contribute to inflammatory functions in various components of innate immunity, such as neutrophils, dendritic cells, mast cells, and epithelial cells.

PMID 20511350

HIF1A, the most ubiquitously expressed hypoxia-inducible factor (HIF), in epithelial cells alters the lung's innate immune response and biases the tissue toward a Th2-mediated inflammation.

PMID 21685248

HIF1A, under normoxic conditions, accumulates in dendritic cells via the TLR/MYD88/NFkB signalling pathway to induce a distinct subset of proinflammatory genes in comparison to hypoxia-induced HIF1A. (Demonstrated in murine model)

PMID 25746953

HIF1A mediates the functional plasticity of monocytes during sepsis, wherein they transit from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodelling .

InnateDB Annotation from Orthologs

Summary

PMID 21685248

[Mus musculus] Hif1a, under normoxic conditions, accumulates in dendritic cells via the TLR/Myd88/NFkB signalling pathway to induce a distinct subset of proinflammatory genes in comparison to hypoxia-induced Hif1a.

Entrez Gene

Summary

This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 14:61695513-61748259

Strand

Forward strand

Band

q23.2

Transcripts

ENST00000337138	ENSP00000338018
ENST00000323441	ENSP00000323326
ENST00000394997	ENSP00000378446
ENST00000557446
ENST00000553999
ENST00000557538	ENSP00000451696
ENST00000557206
ENST00000556237
ENST00000555014
ENST00000547430
ENST00000556827
ENST00000539097	ENSP00000437955

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 258 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	262 [view]
Protein-Protein	220 [view]
Protein-DNA	38 [view]
Protein-RNA	1 [view]
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000989	transcription factor binding transcription factor activity
GO:0001076	RNA polymerase II transcription factor binding transcription factor activity
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0035035	histone acetyltransferase binding
GO:0035257	nuclear hormone receptor binding
GO:0042826	histone deacetylase binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding
GO:0046982	protein heterodimerization activity
GO:0046983	protein dimerization activity
GO:0051879	Hsp90 protein binding

Biological Process

GO:0001525	angiogenesis
GO:0001568	blood vessel development
GO:0001666	response to hypoxia
GO:0001755	neural crest cell migration
GO:0001837	epithelial to mesenchymal transition
GO:0001892	embryonic placenta development
GO:0001922	B-1 B cell homeostasis
GO:0001938	positive regulation of endothelial cell proliferation
GO:0001944	vasculature development
GO:0001947	heart looping
GO:0002052	positive regulation of neuroblast proliferation
GO:0002248	connective tissue replacement involved in inflammatory response wound healing
GO:0003151	outflow tract morphogenesis
GO:0003208	cardiac ventricle morphogenesis
GO:0006089	lactate metabolic process
GO:0006110	regulation of glycolytic process
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006879	cellular iron ion homeostasis
GO:0007165	signal transduction
GO:0007219	Notch signaling pathway
GO:0007595	lactation
GO:0008542	visual learning
GO:0010468	regulation of gene expression
GO:0010573	vascular endothelial growth factor production
GO:0010575	positive regulation vascular endothelial growth factor production
GO:0010634	positive regulation of epithelial cell migration
GO:0010870	positive regulation of receptor biosynthetic process
GO:0014850	response to muscle activity
GO:0019896	axon transport of mitochondrion
GO:0021502	neural fold elevation formation
GO:0021987	cerebral cortex development
GO:0030154	cell differentiation
GO:0030502	negative regulation of bone mineralization
GO:0030949	positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0032007	negative regulation of TOR signaling
GO:0032364	oxygen homeostasis
GO:0032722	positive regulation of chemokine production
GO:0032909	regulation of transforming growth factor beta2 production
GO:0032963	collagen metabolic process
GO:0035162	embryonic hemopoiesis
GO:0035774	positive regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0042127	regulation of cell proliferation
GO:0042541	hemoglobin biosynthetic process
GO:0042593	glucose homeostasis
GO:0042789	mRNA transcription from RNA polymerase II promoter
GO:0043066	negative regulation of apoptotic process
GO:0043524	negative regulation of neuron apoptotic process
GO:0043619	regulation of transcription from RNA polymerase II promoter in response to oxidative stress
GO:0045087	innate immune response (InnateDB)
GO:0045648	positive regulation of erythrocyte differentiation
GO:0045766	positive regulation of angiogenesis
GO:0045821	positive regulation of glycolytic process
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045926	negative regulation of growth
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046716	muscle cell cellular homeostasis
GO:0046886	positive regulation of hormone biosynthetic process
GO:0048514	blood vessel morphogenesis
GO:0048546	digestive tract morphogenesis
GO:0050790	regulation of catalytic activity
GO:0051000	positive regulation of nitric-oxide synthase activity
GO:0051216	cartilage development
GO:0051541	elastin metabolic process
GO:0060574	intestinal epithelial cell maturation
GO:0061030	epithelial cell differentiation involved in mammary gland alveolus development
GO:0061298	retina vasculature development in camera-type eye
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0061419	positive regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070101	positive regulation of chemokine-mediated signaling pathway
GO:0070243	regulation of thymocyte apoptotic process
GO:0070244	negative regulation of thymocyte apoptotic process
GO:0071347	cellular response to interleukin-1
GO:0071456	cellular response to hypoxia
GO:0071542	dopaminergic neuron differentiation
GO:2001054	negative regulation of mesenchymal cell apoptotic process

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0031514	motile cilium