Protein: Hypoxia-inducible factor 3-alpha (HIF-3-alpha) (HIF3-alpha) (HIF3-alpha-1) (Q9JHS2)
Organism: Rattus norvegicus (Rat)
Function: Acts as a transcriptional regulator in adaptive response to low oxygen tension. Attenuates the ability of transcription factor HIF1A, EPAS1 and the HIF1A-ARNT complex to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. 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. May act as a tumor suppressor.
Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:11237857}. Cytoplasm {ECO:0000269|PubMed:11237857}. Nucleus speckle {ECO:0000250|UniProtKB:Q0VBL6}. Mitochondrion {ECO:0000250|UniProtKB:Q0VBL6}. Note=In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes (PubMed:11237857). Localized in the cytoplasm and nuclei under normoxia, but increased in the nucleus under hypoxic conditions. Colocalized with HIF1A in kidney tumors. Colocalizes with BAD in the cytoplasm. Colocalizes with EPAS1 and HIF1A in the nucleus and speckles. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. {ECO:0000250|UniProtKB:Q0VBL6, ECO:0000250|UniProtKB:Q9Y2N7}.
Sequence: MDWDQDRSSTELRKEKSRDAARSRRSQETEVLYQLAHTLPFARGVSAHLDKASIMRLTISYLRMHRLCAAGEWNQVRKEGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQLELIGHSIFDFIHPCDQEELQDALTPRPSLSKKKSEAATGRHFSLRMKSTLTSRGRALNLKAATWKVLHCSGHMRAYKPPAQTSPAGSPRSEPPLQCLVLICEAIPHPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIHALDSDAVSRSIHTLLSKGQAVTGQYRFLARTGGYLWTQTQATVVSGGRGPQSESIICVHFLISRVEENGVVLSLEQTEQHTRRPPQLGTSSKKGIPGNSLDPPAPRILAFLHPPALSEASLAADPRRFCSPDLRRLMAPILDGPPTAATPSTPQAARRPQSPLPADLPDQLAVGLENAHRLSTARKNKTMETDLDIAQDPDTPDLEMLAPYISMDDDFQLNSSEQLPKVHRRPPRTARRPRARSFHGLSPPIPEATLLPRWGSDPRLNCSSPSKGDPPTAPLTPRTRKRALAQSSEDKGLELLETKPPKRSPRLEPGSVLLPPLSLSFLLQGRQLPGNQPDPRAPLVDSHEPLGLAPSLLSLYQHEETIQSRNHFLPAAGLAQTH
InterPro domains: - IPR013767: PAS fold (domain) [90-144]
- IPR000014: PAS domain (domain) [82-336]
- IPR036638: Helix-loop-helix DNA-binding domain superfamily (homologous_superfamily) [2-68]
- IPR011598: Myc-type, basic helix-loop-helix (bHLH) domain (domain) [4-73]
- IPR035965: PAS domain superfamily (homologous_superfamily) [91-339]
- IPR021537: Hypoxia-inducible factor, alpha subunit-like (domain) [475-504]
Interaction partners: - Aryl hydrocarbon receptor nuclear translocator
- Hypoxia-inducible factor 1-alpha
- Endothelial PAS domain-containing protein 1
- Aryl hydrocarbon receptor nuclear translocator 2
- Prolyl hydroxylase EGLN3
- Prolyl hydroxylase EGLN2
- von Hippel-Lindau disease tumor suppressor
- Egl nine homolog 1
- Elongin-C
- Cullin 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0044877 (protein-containing complex binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0003677 (DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0048511 (rhythmic process), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009628 (response to abiotic stimulus), GO:0009058 (biosynthetic process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0007623 (circadian rhythm), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0009314 (response to radiation), GO:0060255 (regulation of macromolecule metabolic process), GO:0044249 (cellular biosynthetic process), GO:1901700 (response to oxygen-containing compound), GO:0031324 (negative regulation of cellular metabolic process), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0009891 (positive regulation of biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901698 (response to nitrogen compound), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0032922 (circadian regulation of gene expression), GO:1901652 (response to peptide), GO:0009059 (macromolecule biosynthetic process), GO:0009416 (response to light stimulus), GO:1901362 (organic cyclic compound biosynthetic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0048545 (response to steroid hormone), GO:0010468 (regulation of gene expression), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0043434 (response to peptide hormone), GO:0010243 (response to organonitrogen compound), GO:0033993 (response to lipid), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0014070 (response to organic cyclic compound), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010467 (gene expression), GO:0016070 (RNA metabolic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0032774 (RNA biosynthetic process), GO:0097659 (nucleic acid-templated transcription), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006351 (DNA-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)