Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (  ). Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis (By similarity).
Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Also inhibits hypoxia-inducible ARNT-mediated gene expression.
Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.
Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation ( , ). May act as a tumor suppressor and inhibits malignant cell transformation .
Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.
Subcellular locations: Nucleus, Cytoplasm, Nucleus speckle, Mitochondrion
In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Colocalizes with BAD in the cytoplasm. Colocalizes with EPAS1 and HIF1A in the nucleus and speckles (By similarity). Localized in the cytoplasm and nuclei under normoxia, but increased in the nucleus under hypoxic conditions . Colocalized with HIF1A in kidney tumors .
Expressed in vascular cells (at protein level) . Expressed in kidney (, ). Expressed in lung epithelial cells . Expressed in endothelial cells (venous and arterial cells from umbilical cord and aortic endothelial cells) and in vascular smooth muscle cells (aorta) . Strongly expressed in the heart, placenta, and skeletal muscle, whereas a weak expression profile was found in the lung, liver, and kidney . Expressed weakly in cell renal cell carcinoma (CC-RCC) compared to normal renal cells . Expression is down-regulated in numerous kidney tumor cells compared to non tumor kidney tissues . Isoform 2 is expressed in heart, placenta, lung, liver, skeletal muscle and pancreas and in numerous cancer cell lines . Isoform 3 and isoform 4 are weakly expressed in heart, placenta, lung, liver, skeletal muscle and pancreas . Isoform 4 is expressed in fetal tissues, such as heart, brain, thymus, lung, liver, skeletal kidney and spleen . Isoform 3 is weakly expressed in fetal tissues, such as liver and kidney .