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
hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
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.
HIF1A expression is regulated by intracellular calcium levels, resulting in modulation of PPP3CA (calcineurin) activity and RACK1 dimerization.
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.
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.
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)
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
[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
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
Cellular responses to stress pathway
Circadian Clock pathway
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant pathway
NOTCH1 Intracellular Domain Regulates Transcription pathway
Signaling by NOTCH1 in Cancer pathway
FBXW7 Mutants and NOTCH1 in Cancer pathway
Signal Transduction pathway
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha pathway
Regulation of Hypoxia-inducible Factor (HIF) by oxygen pathway
Signaling by NOTCH1 PEST Domain Mutants in Cancer pathway
Cellular response to hypoxia pathway
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer pathway
Signaling by NOTCH pathway
Signaling by NOTCH1 pathway
Signaling by NOTCH1 HD Domain Mutants in Cancer pathway
Regulation of gene expression by Hypoxia-inducible Factor pathway
Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha pathway
Disease pathway
KEGG
mTOR signaling pathway pathway
Pathways in cancer pathway
Renal cell carcinoma pathway
INOH
PID BIOCARTA
Hypoxia-inducible factor in the cardivascular system [Biocarta view]
Vegf hypoxia and angiogenesis [Biocarta view]
Hypoxia and p53 in the cardiovascular system [Biocarta view]
Erythropoietin mediated neuroprotection through nf-kb [Biocarta view]
PID NCI
Notch-mediated HES/HEY network
AP-1 transcription factor network
HIF-1-alpha transcription factor network
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha
VEGFR1 specific signals
Cross-References
SwissProt
TrEMBL B4E2U7 F8W9L0
UniProt Splice Variant
Entrez Gene 3091
UniGene Hs.597216 Hs.630364 Hs.719495
RefSeq NM_001243084 NM_001530 NM_181054
HUGO HGNC:4910
OMIM 603348
CCDS CCDS58324 CCDS9753 CCDS9754
HPRD 04517
IMGT
EMBL AK304436 AL137129
GenPept BAG65259
RNA Seq Atlas 3091