HIF1A - Hypoxia-inducible factor 1-alpha - human protein (Function)
 
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HIF1A »  Hypoxia-inducible factor 1-alpha  (HIF1-alpha)
 
Protein also known as:  Class E basic helix-loop-helix protein 78 (bHLHe78).
Gene name:  HIF1A
Entry whose protein(s) existence is based on evidence at protein level
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1 1769 3
GENE REF ISO

Function

 show evidences
Overview 
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 CREBPB 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.  
11
  • UniProtKB
GO molecular function 
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
Histone acetyltransferase bindingdefinition[GO:0035035]  
1
  • UniProtKB
Histone deacetylase bindingdefinition[GO:0042826] silver  
1
  • Ortholog Compara
Hsp90 protein bindingdefinition[GO:0051879]  
1
  • BHF-UCL
Nuclear hormone receptor bindingdefinition[GO:0035257]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
36
  • UniProtKB
  • ParkinsonsUK-UCL
  • IntAct
Protein heterodimerization activitydefinition[GO:0046982]  
3
  • UniProtKB
  • BHF-UCL
Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcriptiondefinition[GO:0001077] silver  
1
  • Ortholog Compara
Contributes to RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activitydefinition[GO:0003705]  
4
  • BHF-UCL
RNA polymerase II transcription factor binding transcription factor activitydefinition[GO:0001076] silver  
1
  • Ortholog Compara
Contributes to sequence-specific DNA bindingdefinition[GO:0043565]  
3
  • BHF-UCL
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
3
  • UniProtKB
  • MGI
Signal transducer activitydefinition[GO:0004871] silver  
1
  • InterPro 2 GO
Transcription factor bindingdefinition[GO:0008134]  
1
  • BHF-UCL
Transcription factor binding transcription factor activitydefinition[GO:0000989]  
1
  • BHF-UCL
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
GO biological process 
Angiogenesisdefinition[GO:0001525] silver  
1
  • Ortholog Compara
Axon transport of mitochondriondefinition[GO:0019896]  
1
  • UniProtKB
B-1 B cell homeostasisdefinition[GO:0001922] silver  
1
  • Ortholog Compara
Cardiac ventricle morphogenesisdefinition[GO:0003208] silver  
1
  • Ortholog Compara
Cartilage developmentdefinition[GO:0051216] silver  
1
  • Ortholog Compara
Cellular iron ion homeostasisdefinition[GO:0006879] silver  
1
  • Ortholog Compara
Cellular response to hypoxiadefinition[GO:0071456]  
4
  • UniProtKB
Cellular response to interleukin-1definition[GO:0071347]  
1
  • BHF-UCL
Cerebral cortex developmentdefinition[GO:0021987] silver  
1
  • Ortholog Compara
Collagen metabolic processdefinition[GO:0032963]  
1
  • BHF-UCL
Connective tissue replacement involved in inflammatory response wound healingdefinition[GO:0002248]  
1
  • BHF-UCL
Digestive tract morphogenesisdefinition[GO:0048546] silver  
1
  • Ortholog Compara
Dopaminergic neuron differentiationdefinition[GO:0071542] silver  
1
  • Ortholog Compara
Elastin metabolic processdefinition[GO:0051541]  
1
  • BHF-UCL
Embryonic hemopoiesisdefinition[GO:0035162] silver  
1
  • Ortholog Compara
Embryonic placenta developmentdefinition[GO:0001892] silver  
1
  • Ortholog Compara
Epithelial cell differentiation involved in mammary gland alveolus developmentdefinition[GO:0061030] silver  
1
  • Ortholog Compara
Epithelial to mesenchymal transitiondefinition[GO:0001837]  
1
  • BHF-UCL
Glucose homeostasisdefinition[GO:0042593] silver  
1
  • Ortholog Compara
Heart loopingdefinition[GO:0001947] silver  
1
  • Ortholog Compara
Hemoglobin biosynthetic processdefinition[GO:0042541] silver  
1
  • Ortholog Compara
Intestinal epithelial cell maturationdefinition[GO:0060574] silver  
1
  • Ortholog Compara
Lactate metabolic processdefinition[GO:0006089] silver  
1
  • Ortholog Compara
Lactationdefinition[GO:0007595] silver  
1
  • Ortholog Compara
mRNA transcription from RNA polymerase II promoterdefinition[GO:0042789]  
1
  • BHF-UCL
Muscle cell cellular homeostasisdefinition[GO:0046716] silver  
1
  • Ortholog Compara
Negative regulation of bone mineralizationdefinition[GO:0030502] silver  
1
  • Ortholog Compara
Negative regulation of growthdefinition[GO:0045926] silver  
1
  • Ortholog Compara
Negative regulation of mesenchymal cell apoptotic processdefinition[GO:2001054] silver  
1
  • Ortholog Compara
Negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathwaydefinition[GO:1903377]  
1
  • ParkinsonsUK-UCL
Negative regulation of thymocyte apoptotic processdefinition[GO:0070244] silver  
1
  • Ortholog Compara
Negative regulation of TOR signalingdefinition[GO:0032007] silver  
1
  • Ortholog Compara
Neural crest cell migrationdefinition[GO:0001755] silver  
1
  • Ortholog Compara
Neural fold elevation formationdefinition[GO:0021502] silver  
1
  • Ortholog Compara
Outflow tract morphogenesisdefinition[GO:0003151] silver  
1
  • Ortholog Compara
Oxygen homeostasisdefinition[GO:0032364]  
1
  • HGNC
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • BHF-UCL
Positive regulation of chemokine productiondefinition[GO:0032722]  
1
  • BHF-UCL
Positive regulation of chemokine-mediated signaling pathwaydefinition[GO:0070101]  
1
  • BHF-UCL
Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
1
  • BHF-UCL
Positive regulation of epithelial cell migrationdefinition[GO:0010634]  
1
  • BHF-UCL
Positive regulation of erythrocyte differentiationdefinition[GO:0045648]  
1
  • BHF-UCL
Positive regulation of glycolytic processdefinition[GO:0045821]  
1
  • BHF-UCL
Positive regulation of hormone biosynthetic processdefinition[GO:0046886]  
1
  • BHF-UCL
Positive regulation of insulin secretion involved in cellular response to glucose stimulusdefinition[GO:0035774] silver  
1
  • Ortholog Compara
Positive regulation of neuroblast proliferationdefinition[GO:0002052] silver  
1
  • Ortholog Compara
Positive regulation of nitric-oxide synthase activitydefinition[GO:0051000]  
1
  • BHF-UCL
Positive regulation of receptor biosynthetic processdefinition[GO:0010870]  
1
  • BHF-UCL
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
3
  • MGI
  • UniProtKB
Positive regulation of transcription from RNA polymerase II promoter in response to hypoxiadefinition[GO:0061419]  
3
  • UniProtKB
  • BHF-UCL
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
3
  • UniProtKB
  • BHF-UCL
Positive regulation of vascular endothelial growth factor productiondefinition[GO:0010575]  
2
  • UniProtKB
  • BHF-UCL
Positive regulation of vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0030949]  
2
  • BHF-UCL
Regulation of gene expressiondefinition[GO:0010468]  
1
  • UniProtKB
Regulation of transcription from RNA polymerase II promoter in response to oxidative stressdefinition[GO:0043619]  
2
  • BHF-UCL
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
2
  • UniProtKB
  • MGI
Regulation of transforming growth factor beta2 productiondefinition[GO:0032909]  
1
  • BHF-UCL
Response to hypoxiadefinition[GO:0001666]  
6
  • UniProtKB
  • BHF-UCL
  • MGI
Response to muscle activitydefinition[GO:0014850] silver  
1
  • Ortholog Compara
Retina vasculature development in camera-type eyedefinition[GO:0061298] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • BHF-UCL
Vascular endothelial growth factor productiondefinition[GO:0010573]  
1
  • BHF-UCL
Visual learningdefinition[GO:0008542] silver  
1
  • Ortholog Compara
Pathways 
According to KEGG, this protein belongs to the following pathways:
mTOR signaling pathway  hsa04150+3091  
Pathways in cancer  hsa05200+3091  
Renal cell carcinoma  hsa05211+3091  
According to Reactome, this protein belongs to the following pathways:
Circadian Clock  REACT_24941  
NOTCH1 Intracellular Domain Regulates Transcription  REACT_118780  
Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha  REACT_121226  
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha  REACT_120916  
Regulation of gene expression by Hypoxia-inducible Factor  REACT_121092  
 

Keywords

Biological process 
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: HIF1A
GenomeRNAi: 3091
PRO: PR:Q16665