Hif1a;

Hypoxia-inducible factor 1-alpha(HIF-1-alpha;HIF1-alpha);

Rat (Rattus norvegicus). 

Interacts with COPS5 subunit of COP9 signalosome complex, leading to the regulation of its stability. Efficient DNA binding requires heterodimerization of an alpha and a beta/ARNT subunit. Interacts with NCOA1, NCOA2, APEX, HSP90 and TSGA10. Interacts with VHL which docks HFA1 to the E3 ubiquitin ligase complex for subsequent destruction. Interaction, via the ODD domain, with the beta domain of VHLL, protects HIF1A from destruction by competing against the destructive targeting initiated by VHL. Interacts with RORA (via the DNA bi nding 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 (By similarity). Interacts with USP20. Interacts with GNB2L1/RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation Interacts with EP300 (via TAZ-type 1 domain); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domain).

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, 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.

Cytoplasm Nucleus Cytoplasmic in normoxia, nuclear translocation in response to hypoxia.

825

N/A

Please Sign in.

O35800

10116.ENSRNOP00000042230

Rn.10852

O35800

PF11413

rno:29560