||Purified Polyclonal HIF1A antibody specific for human HIF1A for use in Immunohistochemistry and Western blot
HIF1A is 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. HIF1A 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.
||HIF1A is up-regulated in peripheral T lymphocytes after T-cell receptor stimulation. Highest expression in peripheral blood leukocytes and thymus. HIF1A is located in the cytoplasm and nucleus. It is cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia. HIF1A is expressed in most tissues with highest levels in kidney and heart and is commonly overexpressed in the majority of common human cancers and their metastases.
|Implications in Disease
||Overexpression of a natural antisense transcript (aHIF) of the HIF1A gene is associated with nonpapillary renal carcinomas.
||HIF1A contains a bHLH domain at amino acids 17 – 70, contains a PAS 1 domain at amino acids 85 – 158, a PAS 2 domain at amino acids 228 – 298 and a PAC domain at amino acids 302 – 345.
||HIF1A is hydroxylated on Pro-402 and Pro-564 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD1 and EGLN2/PHD2. EGLN3/PHD3 has also been shown to hydroxylate Pro-564. In normoxia, HIF1A is hydroxylated on Asn-803 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Sumoylated: HIF1A is sumyolated with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Desumoylation by SENP1 leads to increased HIF1A stability and transriptional activity.
||Entrez Gene: 3091 Human, Omim: 603348 Human, SwissProt: Q16665 Human, Unigene: 597216 Human