Browse HIF1A

Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus Nucleus speckle Note=Colocalizes with HIF3A in the nucleus and speckles (By similarity). Cytoplasmic in normoxia, nuclear translocation in response to hypoxia (PubMed:9822602).
Domain PF11413 Hypoxia-inducible factor-1
PF08778 HIF-1 alpha C terminal transactivation domain
PF00989 PAS fold
PF08447 PAS fold
Function

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.

> Gene Ontology
 
Biological Process GO:0000422 mitophagy
GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001525 angiogenesis
GO:0001654 eye development
GO:0001666 response to hypoxia
GO:0001667 ameboidal-type cell migration
GO:0001678 cellular glucose homeostasis
GO:0001701 in utero embryonic development
GO:0001755 neural crest cell migration
GO:0001776 leukocyte homeostasis
GO:0001782 B cell homeostasis
GO:0001819 positive regulation of cytokine production
GO:0001837 epithelial to mesenchymal transition
GO:0001838 embryonic epithelial tube formation
GO:0001841 neural tube formation
GO:0001842 neural fold formation
GO:0001890 placenta development
GO:0001892 embryonic placenta development
GO:0001922 B-1 B cell homeostasis
GO:0001935 endothelial cell proliferation
GO:0001936 regulation of endothelial cell proliferation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0001947 heart looping
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0001961 positive regulation of cytokine-mediated signaling pathway
GO:0002052 positive regulation of neuroblast proliferation
GO:0002064 epithelial cell development
GO:0002065 columnar/cuboidal epithelial cell differentiation
GO:0002066 columnar/cuboidal epithelial cell development
GO:0002069 columnar/cuboidal epithelial cell maturation
GO:0002070 epithelial cell maturation
GO:0002246 wound healing involved in inflammatory response
GO:0002248 connective tissue replacement involved in inflammatory response wound healing
GO:0002260 lymphocyte homeostasis
GO:0002262 myeloid cell homeostasis
GO:0002790 peptide secretion
GO:0002791 regulation of peptide secretion
GO:0002793 positive regulation of peptide secretion
GO:0003007 heart morphogenesis
GO:0003143 embryonic heart tube morphogenesis
GO:0003151 outflow tract morphogenesis
GO:0003205 cardiac chamber development
GO:0003206 cardiac chamber morphogenesis
GO:0003208 cardiac ventricle morphogenesis
GO:0003231 cardiac ventricle development
GO:0006089 lactate metabolic process
GO:0006090 pyruvate metabolic process
GO:0006091 generation of precursor metabolites and energy
GO:0006096 glycolytic process
GO:0006109 regulation of carbohydrate metabolic process
GO:0006110 regulation of glycolytic process
GO:0006140 regulation of nucleotide metabolic process
GO:0006165 nucleoside diphosphate phosphorylation
GO:0006732 coenzyme metabolic process
GO:0006733 oxidoreduction coenzyme metabolic process
GO:0006757 ATP generation from ADP
GO:0006875 cellular metal ion homeostasis
GO:0006879 cellular iron ion homeostasis
GO:0006914 autophagy
GO:0006979 response to oxidative stress
GO:0007018 microtubule-based movement
GO:0007368 determination of left/right symmetry
GO:0007389 pattern specification process
GO:0007405 neuroblast proliferation
GO:0007423 sensory organ development
GO:0007507 heart development
GO:0007589 body fluid secretion
GO:0007595 lactation
GO:0007611 learning or memory
GO:0007612 learning
GO:0007632 visual behavior
GO:0008088 axo-dendritic transport
GO:0008306 associative learning
GO:0008542 visual learning
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0009060 aerobic respiration
GO:0009100 glycoprotein metabolic process
GO:0009116 nucleoside metabolic process
GO:0009118 regulation of nucleoside metabolic process
GO:0009119 ribonucleoside metabolic process
GO:0009123 nucleoside monophosphate metabolic process
GO:0009126 purine nucleoside monophosphate metabolic process
GO:0009132 nucleoside diphosphate metabolic process
GO:0009135 purine nucleoside diphosphate metabolic process
GO:0009141 nucleoside triphosphate metabolic process
GO:0009144 purine nucleoside triphosphate metabolic process
GO:0009150 purine ribonucleotide metabolic process
GO:0009161 ribonucleoside monophosphate metabolic process
GO:0009167 purine ribonucleoside monophosphate metabolic process
GO:0009179 purine ribonucleoside diphosphate metabolic process
GO:0009185 ribonucleoside diphosphate metabolic process
GO:0009199 ribonucleoside triphosphate metabolic process
GO:0009205 purine ribonucleoside triphosphate metabolic process
GO:0009299 mRNA transcription
GO:0009306 protein secretion
GO:0009314 response to radiation
GO:0009416 response to light stimulus
GO:0009743 response to carbohydrate
GO:0009746 response to hexose
GO:0009749 response to glucose
GO:0009799 specification of symmetry
GO:0009855 determination of bilateral symmetry
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0009914 hormone transport
GO:0010506 regulation of autophagy
GO:0010508 positive regulation of autophagy
GO:0010573 vascular endothelial growth factor production
GO:0010574 regulation of vascular endothelial growth factor production
GO:0010575 positive regulation of vascular endothelial growth factor production
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0010720 positive regulation of cell development
GO:0010817 regulation of hormone levels
GO:0010821 regulation of mitochondrion organization
GO:0010822 positive regulation of mitochondrion organization
GO:0010869 regulation of receptor biosynthetic process
GO:0010870 positive regulation of receptor biosynthetic process
GO:0010970 transport along microtubule
GO:0014020 primary neural tube formation
GO:0014031 mesenchymal cell development
GO:0014032 neural crest cell development
GO:0014033 neural crest cell differentiation
GO:0014823 response to activity
GO:0014850 response to muscle activity
GO:0015833 peptide transport
GO:0015980 energy derivation by oxidation of organic compounds
GO:0016052 carbohydrate catabolic process
GO:0016236 macroautophagy
GO:0016239 positive regulation of macroautophagy
GO:0016241 regulation of macroautophagy
GO:0016331 morphogenesis of embryonic epithelium
GO:0019362 pyridine nucleotide metabolic process
GO:0019896 axonal transport of mitochondrion
GO:0020027 hemoglobin metabolic process
GO:0021502 neural fold elevation formation
GO:0021537 telencephalon development
GO:0021543 pallium development
GO:0021700 developmental maturation
GO:0021915 neural tube development
GO:0021987 cerebral cortex development
GO:0023061 signal release
GO:0030072 peptide hormone secretion
GO:0030073 insulin secretion
GO:0030099 myeloid cell differentiation
GO:0030218 erythrocyte differentiation
GO:0030278 regulation of ossification
GO:0030279 negative regulation of ossification
GO:0030282 bone mineralization
GO:0030335 positive regulation of cell migration
GO:0030500 regulation of bone mineralization
GO:0030502 negative regulation of bone mineralization
GO:0030705 cytoskeleton-dependent intracellular transport
GO:0030879 mammary gland development
GO:0030900 forebrain development
GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway
GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0031214 biomineral tissue development
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031929 TOR signaling
GO:0032006 regulation of TOR signaling
GO:0032007 negative regulation of TOR signaling
GO:0032024 positive regulation of insulin secretion
GO:0032350 regulation of hormone metabolic process
GO:0032352 positive regulation of hormone metabolic process
GO:0032364 oxygen homeostasis
GO:0032602 chemokine production
GO:0032642 regulation of chemokine production
GO:0032722 positive regulation of chemokine production
GO:0032768 regulation of monooxygenase activity
GO:0032770 positive regulation of monooxygenase activity
GO:0032800 receptor biosynthetic process
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032906 transforming growth factor beta2 production
GO:0032909 regulation of transforming growth factor beta2 production
GO:0032941 secretion by tissue
GO:0032963 collagen metabolic process
GO:0033483 gas homeostasis
GO:0033500 carbohydrate homeostasis
GO:0034101 erythrocyte homeostasis
GO:0034284 response to monosaccharide
GO:0034599 cellular response to oxidative stress
GO:0034643 establishment of mitochondrion localization, microtubule-mediated
GO:0035050 embryonic heart tube development
GO:0035148 tube formation
GO:0035162 embryonic hemopoiesis
GO:0035239 tube morphogenesis
GO:0035773 insulin secretion involved in cellular response to glucose stimulus
GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0036003 positive regulation of transcription from RNA polymerase II promoter in response to stress
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0036473 cell death in response to oxidative stress
GO:0036475 neuron death in response to oxidative stress
GO:0036480 neuron intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0040017 positive regulation of locomotion
GO:0042278 purine nucleoside metabolic process
GO:0042445 hormone metabolic process
GO:0042446 hormone biosynthetic process
GO:0042541 hemoglobin biosynthetic process
GO:0042593 glucose homeostasis
GO:0042789 mRNA transcription from RNA polymerase II promoter
GO:0042886 amide transport
GO:0043010 camera-type eye development
GO:0043112 receptor metabolic process
GO:0043457 regulation of cellular respiration
GO:0043467 regulation of generation of precursor metabolites and energy
GO:0043470 regulation of carbohydrate catabolic process
GO:0043523 regulation of neuron apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043619 regulation of transcription from RNA polymerase II promoter in response to oxidative stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0044236 multicellular organism metabolic process
GO:0044259 multicellular organismal macromolecule metabolic process
GO:0044708 single-organism behavior
GO:0044723 single-organism carbohydrate metabolic process
GO:0044724 single-organism carbohydrate catabolic process
GO:0045333 cellular respiration
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045646 regulation of erythrocyte differentiation
GO:0045648 positive regulation of erythrocyte differentiation
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0045821 positive regulation of glycolytic process
GO:0045913 positive regulation of carbohydrate metabolic process
GO:0045926 negative regulation of growth
GO:0045979 positive regulation of nucleoside metabolic process
GO:0045981 positive regulation of nucleotide metabolic process
GO:0046031 ADP metabolic process
GO:0046034 ATP metabolic process
GO:0046128 purine ribonucleoside metabolic process
GO:0046496 nicotinamide nucleotide metabolic process
GO:0046716 muscle cell cellular homeostasis
GO:0046879 hormone secretion
GO:0046883 regulation of hormone secretion
GO:0046885 regulation of hormone biosynthetic process
GO:0046886 positive regulation of hormone biosynthetic process
GO:0046887 positive regulation of hormone secretion
GO:0046916 cellular transition metal ion homeostasis
GO:0046939 nucleotide phosphorylation
GO:0047497 mitochondrion transport along microtubule
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048469 cell maturation
GO:0048514 blood vessel morphogenesis
GO:0048546 digestive tract morphogenesis
GO:0048562 embryonic organ morphogenesis
GO:0048565 digestive tract development
GO:0048568 embryonic organ development
GO:0048592 eye morphogenesis
GO:0048593 camera-type eye morphogenesis
GO:0048608 reproductive structure development
GO:0048732 gland development
GO:0048762 mesenchymal cell differentiation
GO:0048771 tissue remodeling
GO:0048863 stem cell differentiation
GO:0048864 stem cell development
GO:0048872 homeostasis of number of cells
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050769 positive regulation of neurogenesis
GO:0050796 regulation of insulin secretion
GO:0050878 regulation of body fluid levels
GO:0050890 cognition
GO:0050999 regulation of nitric-oxide synthase activity
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:0051047 positive regulation of secretion
GO:0051186 cofactor metabolic process
GO:0051193 regulation of cofactor metabolic process
GO:0051194 positive regulation of cofactor metabolic process
GO:0051196 regulation of coenzyme metabolic process
GO:0051197 positive regulation of coenzyme metabolic process
GO:0051216 cartilage development
GO:0051222 positive regulation of protein transport
GO:0051272 positive regulation of cellular component movement
GO:0051341 regulation of oxidoreductase activity
GO:0051353 positive regulation of oxidoreductase activity
GO:0051402 neuron apoptotic process
GO:0051541 elastin metabolic process
GO:0051640 organelle localization
GO:0051646 mitochondrion localization
GO:0051654 establishment of mitochondrion localization
GO:0051656 establishment of organelle localization
GO:0051962 positive regulation of nervous system development
GO:0055072 iron ion homeostasis
GO:0055076 transition metal ion homeostasis
GO:0055123 digestive system development
GO:0060041 retina development in camera-type eye
GO:0060249 anatomical structure homeostasis
GO:0060485 mesenchyme development
GO:0060562 epithelial tube morphogenesis
GO:0060571 morphogenesis of an epithelial fold
GO:0060574 intestinal epithelial cell maturation
GO:0060575 intestinal epithelial cell differentiation
GO:0060576 intestinal epithelial cell development
GO:0060644 mammary gland epithelial cell differentiation
GO:0060749 mammary gland alveolus development
GO:0060759 regulation of response to cytokine stimulus
GO:0060760 positive regulation of response to cytokine stimulus
GO:0061030 epithelial cell differentiation involved in mammary gland alveolus development
GO:0061072 iris morphogenesis
GO:0061178 regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0061180 mammary gland epithelium development
GO:0061298 retina vasculature development in camera-type eye
GO:0061351 neural precursor cell proliferation
GO:0061371 determination of heart left/right asymmetry
GO:0061377 mammary gland lobule development
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:0061448 connective tissue development
GO:0061458 reproductive system development
GO:0061614 pri-miRNA transcription from RNA polymerase II promoter
GO:0061726 mitochondrion disassembly
GO:0070098 chemokine-mediated signaling pathway
GO:0070099 regulation of chemokine-mediated signaling pathway
GO:0070101 positive regulation of chemokine-mediated signaling pathway
GO:0070167 regulation of biomineral tissue development
GO:0070168 negative regulation of biomineral tissue development
GO:0070227 lymphocyte apoptotic process
GO:0070228 regulation of lymphocyte apoptotic process
GO:0070229 negative regulation of lymphocyte apoptotic process
GO:0070231 T cell apoptotic process
GO:0070232 regulation of T cell apoptotic process
GO:0070233 negative regulation of T cell apoptotic process
GO:0070242 thymocyte apoptotic process
GO:0070243 regulation of thymocyte apoptotic process
GO:0070244 negative regulation of thymocyte apoptotic process
GO:0070482 response to oxygen levels
GO:0070555 response to interleukin-1
GO:0070997 neuron death
GO:0071322 cellular response to carbohydrate stimulus
GO:0071326 cellular response to monosaccharide stimulus
GO:0071331 cellular response to hexose stimulus
GO:0071333 cellular response to glucose stimulus
GO:0071347 cellular response to interleukin-1
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071542 dopaminergic neuron differentiation
GO:0071604 transforming growth factor beta production
GO:0071634 regulation of transforming growth factor beta production
GO:0071887 leukocyte apoptotic process
GO:0072089 stem cell proliferation
GO:0072091 regulation of stem cell proliferation
GO:0072175 epithelial tube formation
GO:0072384 organelle transport along microtubule
GO:0072524 pyridine-containing compound metabolic process
GO:0072593 reactive oxygen species metabolic process
GO:0090087 regulation of peptide transport
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0090276 regulation of peptide hormone secretion
GO:0090277 positive regulation of peptide hormone secretion
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090594 inflammatory response to wounding
GO:0090596 sensory organ morphogenesis
GO:0097152 mesenchymal cell apoptotic process
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097411 hypoxia-inducible factor-1alpha signaling pathway
GO:0097709 connective tissue replacement
GO:0098930 axonal transport
GO:1900407 regulation of cellular response to oxidative stress
GO:1900408 negative regulation of cellular response to oxidative stress
GO:1900542 regulation of purine nucleotide metabolic process
GO:1900544 positive regulation of purine nucleotide metabolic process
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901342 regulation of vasculature development
GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
GO:1901657 glycosyl compound metabolic process
GO:1902175 regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902532 negative regulation of intracellular signal transduction
GO:1902692 regulation of neuroblast proliferation
GO:1902882 regulation of response to oxidative stress
GO:1902883 negative regulation of response to oxidative stress
GO:1902893 regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1903008 organelle disassembly
GO:1903146 regulation of mitophagy
GO:1903201 regulation of oxidative stress-induced cell death
GO:1903202 negative regulation of oxidative stress-induced cell death
GO:1903203 regulation of oxidative stress-induced neuron death
GO:1903204 negative regulation of oxidative stress-induced neuron death
GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:1903532 positive regulation of secretion by cell
GO:1903578 regulation of ATP metabolic process
GO:1903580 positive regulation of ATP metabolic process
GO:1903599 positive regulation of mitophagy
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1903715 regulation of aerobic respiration
GO:1904018 positive regulation of vasculature development
GO:1904951 positive regulation of establishment of protein localization
GO:2000106 regulation of leukocyte apoptotic process
GO:2000107 negative regulation of leukocyte apoptotic process
GO:2000147 positive regulation of cell motility
GO:2000177 regulation of neural precursor cell proliferation
GO:2000179 positive regulation of neural precursor cell proliferation
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000378 negative regulation of reactive oxygen species metabolic process
GO:2000648 positive regulation of stem cell proliferation
GO:2001053 regulation of mesenchymal cell apoptotic process
GO:2001054 negative regulation of mesenchymal cell apoptotic process
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0008134 transcription factor binding
GO:0031072 heat shock protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0035035 histone acetyltransferase binding
GO:0035257 nuclear hormone receptor binding
GO:0042826 histone deacetylase binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0046982 protein heterodimerization activity
GO:0051427 hormone receptor binding
GO:0051879 Hsp90 protein binding
Cellular Component GO:0005667 transcription factor complex
GO:0005929 cilium
GO:0016604 nuclear body
GO:0016607 nuclear speck
GO:0030424 axon
GO:0031514 motile cilium
GO:0032838 cell projection cytoplasm
GO:0033267 axon part
GO:0044798 nuclear transcription factor complex
GO:0090575 RNA polymerase II transcription factor complex
GO:0099568 cytoplasmic region
GO:1904115 axon cytoplasm
> KEGG and Reactome Pathway
 
KEGG hsa04066 HIF-1 signaling pathway
hsa04140 Regulation of autophagy
hsa04919 Thyroid hormone signaling pathway
Reactome R-HSA-1368108: BMAL1
R-HSA-2262749: Cellular response to hypoxia
R-HSA-2262752: Cellular responses to stress
R-HSA-400253: Circadian Clock
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-5688426: Deubiquitination
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-392499: Metabolism of proteins
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-1234162: Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1234176: Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-8849473: PTK6 Expression
R-HSA-8857538: PTK6 promotes HIF1A stabilization
R-HSA-597592: Post-translational protein modification
R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-1234158: Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-8848021: Signaling by PTK6
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HIF1A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between HIF1A and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27245613Cervical CarcinomaInhibit immunityPKA also stimulated the binding of the coactivator p300 to HIF-1α to enhance its transcriptional activity and counteracted the inhibitory effect of asparaginyl hydroxylation on the association of p300 with HIF-1α. Furthermore, increased cAMP concentrations enhanced the expression of HIF target genes encoding CD39 and CD73, which are enzymes that convert extracellular adenosine 5'-triphosphate to adenosine, a molecule that enhances tumor immunosuppression and reduces heart rate and contractility.
26837767Hepatocellular CarcinomaInhibit immunity (T cell function)Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.
26062742Renal Cell CarcinomaInhibit immunity (T cell function; infiltration)Carbonic anhydrase (CA) IX is a surface-expressed protein that is upregulated by the hypoxia inducible factor (HIF) and represents a prototypic tumor-associated antigen that is overexpressed on renal cell carcinoma (RCC). We show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in inhibition of CAIX(+) tumor growth.
25589622E7+ tumor TC-1Inhibit immunity (T cell function)Gain of HIF-1α under normoxia in cancer mediates immune adaptation through the AKT/ERK and VEGFA axes. We found that tumor cells gain HIF-1α in the course of immune selection under normoxia and that HIF-1α renders tumor cells resistant to lysis by tumor-specific cytotoxic T lymphocytes (CTL) in culture and in mice.
24778419Melanoma; Lung Carcinoma; Colon Carcinoma; Breast CarcinomaInhibit immunity (T cell function)Furthermore, PD-L1 up-regulation under hypoxia was dependent on hypoxia-inducible factor-1α (HIF-1α) but not HIF-2α. Chromatin immunoprecipitation and luciferase reporter assay revealed direct binding of HIF-1α to a transcriptionally active hypoxia-response element (HRE) in the PD-L1 proximal promoter. Blockade of PD-L1 under hypoxia enhanced MDSC-mediated T cell activation and was accompanied by the down-regulation of MDSCs IL-6 and IL-10. Finally, neutralizing antibodies against IL-10 under hypoxia significantly abrogated the suppressive activity of MDSCs.
29136509MelanomaPromote immunityFurthermore, loss of HIF-1α in CD8+ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization.
24336068Prostate Carcinoma; Breast CarcinomaInhibit immunityExposure of human or murine cancer cells to hypoxia for 24 hours led to upregulation of the immune inhibitory molecule programmed cell death ligand-1 (PD-L1; also known as B7-H1), in a manner dependent on the transcription factor hypoxia-inducible factor-1α (HIF-1α). Using glyceryl trinitrate (GTN), an agonist of nitric oxide (NO) signaling known to block HIF-1α accumulation in hypoxic cells, we prevented hypoxia-induced PD-L1 expression and diminished resistance to CTL-mediated lysis.
22006996Prostate Carcinoma; Breast CarcinomaPromote immunityIndeed, our findings show a mechanistic link between hypoxia-induced accumulation of the α-subunit of HIF-1 (HIF-1α), increased expression of ADAM10, and decreased surface MICA levels leading to tumor cell resistance to lysis mediated by innate immune effectors.
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of HIF1A in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of HIF1A in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0970.845
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.5490.82
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2210.892
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3170.406
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.8020.743
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3050.928
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0110.983
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0660.973
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0920.965
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0480.976
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.6890.768
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1920.0545
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HIF1A in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382707.4-7.40.169
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HIF1A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HIF1A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HIF1A.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HIF1A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HIF1A expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HIF1A and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHIF1A
Namehypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Aliases MOP1; HIF-1alpha; PASD8; HIF1; bHLHe78; HIF-1-alpha; HIF-1A; HIF1-ALPHA; ARNT interacting protein; ARNT-inte ......
Chromosomal Location14q23.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HIF1A collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting HIF1A.
ID Name Drug Type Targets #Targets
DB01136CarvedilolSmall MoleculeADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, GJA1 ......17
DB023422-MethoxyestradiolSmall MoleculeCOMT, CYP19A1, CYP1A1, CYP1B1, HIF1A5
DB05959ENMD-1198Small MoleculeHIF1A, STAT3, TNFRSF11A3
DB06082PX-478Small MoleculeHIF1A1
DB08687FG-2216Small MoleculeEGLN1, HIF1A2