UniProt functional annotation for P97481



	UniProt functional annotation for P97481

UniProt code: P97481.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity). {ECO:0000250, ECO:0000269|PubMed:26245371}.

Subunit: Interacts with HIF3A isoform 2 (PubMed:21546903). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'- TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Interacts with CREBBP (PubMed:11983697). Interacts with EGLN1. Interacts with VHL (By similarity). {ECO:0000250|UniProtKB:Q99814, ECO:0000269|PubMed:11983697, ECO:0000269|PubMed:21546903, ECO:0000269|PubMed:26245371}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:21546903}. Nucleus speckle {ECO:0000269|PubMed:21546903}. Note=Colocalizes with HIF3A isoform 2 in the nucleus and speckles. {ECO:0000269|PubMed:21546903}.

Tissue specificity: Expressed in most tissues, with highest levels in lung, followed by heart, kidney, brain and liver. Predominantly expressed in endothelial cells. Also found in smooth muscle cells of the uterus, neurons, and brown adipose tissue. High expression in embryonic choroid plexus and kidney glomeruli.

Developmental stage: In day 11 embryo, expression is almost exclusively seen in endothelial cells of the intersegmental blood vessels separating the somites, the atrial and ventricular chambers of the heart, and the dorsal aorta. High expression also occurs in extraembryonic membranes. In the developing brain of day 13 embryo, endothelial cells of the highly vascularized choroid plexus contain high levels of EPAS1.

Ptm: In normoxia, is probably hydroxylated on Pro-405 and Pro-530 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). {ECO:0000250}.

Ptm: In normoxia, is hydroxylated on Asn-851 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. {ECO:0000269|PubMed:11823643}.

Ptm: Phosphorylated on multiple sites in the CTAD. {ECO:0000269|PubMed:11983697}.

Ptm: The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. {ECO:0000269|PubMed:11823643}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity). {ECO:0000250, ECO:0000269\|PubMed:26245371}.


Subunit:		Interacts with HIF3A isoform 2 (PubMed:21546903). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'- TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Interacts with CREBBP (PubMed:11983697). Interacts with EGLN1. Interacts with VHL (By similarity). {ECO:0000250\|UniProtKB:Q99814, ECO:0000269\|PubMed:11983697, ECO:0000269\|PubMed:21546903, ECO:0000269\|PubMed:26245371}.
Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00981, ECO:0000269\|PubMed:21546903}. Nucleus speckle {ECO:0000269\|PubMed:21546903}. Note=Colocalizes with HIF3A isoform 2 in the nucleus and speckles. {ECO:0000269\|PubMed:21546903}.
Tissue specificity:		Expressed in most tissues, with highest levels in lung, followed by heart, kidney, brain and liver. Predominantly expressed in endothelial cells. Also found in smooth muscle cells of the uterus, neurons, and brown adipose tissue. High expression in embryonic choroid plexus and kidney glomeruli.
Developmental stage:		In day 11 embryo, expression is almost exclusively seen in endothelial cells of the intersegmental blood vessels separating the somites, the atrial and ventricular chambers of the heart, and the dorsal aorta. High expression also occurs in extraembryonic membranes. In the developing brain of day 13 embryo, endothelial cells of the highly vascularized choroid plexus contain high levels of EPAS1.
Ptm:		In normoxia, is probably hydroxylated on Pro-405 and Pro-530 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). {ECO:0000250}.
Ptm:		In normoxia, is hydroxylated on Asn-851 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. {ECO:0000269\|PubMed:11823643}.
Ptm:		Phosphorylated on multiple sites in the CTAD. {ECO:0000269\|PubMed:11983697}.
Ptm:		The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. {ECO:0000269\|PubMed:11823643}.