HIF1 Alpha (HIF1A) Antibody – Mouse Monoclonal

This gene encodes the alpha subunit which, along with the beta subunit, forms a heterodimeric transcription factor that regulates the cellular and developmental response to reduced oxygen tension. The transcription factor has been shown to regulate genes involved in several biological processes, including erythropoiesis and angiogenesis which aid in increased delivery of oxygen to hypoxic regions. The transcription factor also plays a role in the induction of genes involved in cell proliferation and survival, energy metabolism, apoptosis, and glucose and iron metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

HIF1A: 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. Interacts with the HIF1A beta/ARNT subunit; heterodimerization is required for DNA binding. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability. Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with TSGA10. Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia- mimicking conditions. Interacts with USP20. Interacts with RACK1; promotes HIF1A ubiquitination and proteasome- mediated degradation. Interacts (via N-terminus) with USP19. Under reduced oxygen tension. Induced also by various receptor-mediated factors such as growth factors, cytokines, and circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, TNF, IL1B, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2 and LIMD1. Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Transcription factor; Autophagy; DNA-binding

Cellular Component: transcription factor complex; cell; cytoplasm; nucleolus; nuclear speck; cytosol; nucleus

Molecular Function: protein dimerization activity; RNA polymerase II transcription factor activity, enhancer binding; histone deacetylase binding; Hsp90 protein binding; transcription factor binding; protein kinase binding; histone acetyltransferase binding; protein binding; signal transducer activity; enzyme binding; DNA binding; sequence-specific DNA binding; protein heterodimerization activity; ubiquitin protein ligase binding; protein complex binding; transcription factor activity; nuclear hormone receptor binding

Biological Process: cellular iron ion homeostasis; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; glucose homeostasis; muscle maintenance; negative regulation of bone mineralization; elastin metabolic process; connective tissue replacement during inflammatory response; axon transport of mitochondrion; regulation of glycolysis; negative regulation of neuron apoptosis; neural crest cell migration; negative regulation of growth; hemoglobin biosynthetic process; positive regulation of neuroblast proliferation; transcription, DNA-dependent; collagen metabolic process; embryonic hemopoiesis; digestive tract morphogenesis; regulation of transcription from RNA polymerase II promoter; neural fold elevation formation; regulation of gene expression; blood vessel morphogenesis; positive regulation of transcription from RNA polymerase II promoter; cerebral cortex development; negative regulation of apoptosis; transcription from RNA polymerase II promoter; lactation; oxygen homeostasis; response to muscle activity; embryonic placenta development; positive regulation of smooth muscle cell proliferation; signal transduction; positive regulation of vascular endothelial growth factor receptor signaling pathway; vasculature development; regulation of transcription, DNA-dependent; regulation of catalytic activity; positive regulation of cell proliferation; visual learning; angiogenesis; heart looping; cell differentiation; regulation of transcription from RNA polymerase II promoter in response to oxidative stress; positive regulation of autophagy; blood vessel development; regulation of transforming growth factor-beta2 production; negative regulation of TOR signaling pathway; positive regulation of erythrocyte differentiation; B-1 B cell homeostasis; negative regulation of vasoconstriction; regulation of cell proliferation; positive regulation of hormone biosynthetic process; cartilage development; lactate metabolic process; response to hypoxia; epithelial to mesenchymal transition