HIF3A

Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.

HIF3A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4WN5
Identifiers
Aliases	HIF3A, HIF-3A, IPAS, MOP7, PASD7, bHLHe17, HIF3-alpha-1, hypoxia inducible factor 3 alpha subunit, hypoxia inducible factor 3 subunit alpha
External IDs	OMIM: 609976; MGI: 1859778; HomoloGene: 9646; GeneCards: HIF3A; OMA:HIF3A - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.32 Start 46,297,042 bp End 46,343,433 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 A2 Start 16,765,432 bp End 16,796,352 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastric mucosa apex of heart right lung left uterine tube muscle layer of sigmoid colon right auricle sural nerve left ventricle popliteal artery tibial arteries Top expressed in fetal liver hematopoietic progenitor cell left lung lobe external carotid artery internal carotid artery fossa human fetus atrium efferent ductule umbilical cord migratory enteric neural crest cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein dimerization activity transcription corepressor activity DNA-binding transcription factor activity transcription coactivator activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm nuclear speck mitochondrion nucleoplasm cytosol plasma membrane nucleus Biological process response to hypoxia regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II transcription by RNA polymerase II transcription, DNA-templated multicellular organism development angiogenesis regulation of transcription from RNA polymerase II promoter in response to hypoxia positive regulation of transcription by RNA polymerase II apoptotic process negative regulation of nucleic acid-templated transcription cellular response to hypoxia post-translational protein modification positive regulation of nucleic acid-templated transcription protein ubiquitination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 64344 53417 Ensembl ENSG00000124440 ENSMUSG00000004328 UniProt Q9Y2N7 Q0VBL6 RefSeq (mRNA) NM_022462 NM_152794 NM_152795 NM_152796 NM_001162950 NM_016868 RefSeq (protein) NP_071907 NP_690007 NP_690008 NP_690009 NP_001156422 NP_058564 Location (UCSC) Chr 19: 46.3 – 46.34 Mb Chr 7: 16.77 – 16.8 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. At least three transcript variants encoding three different isoforms have been found for this gene.

In rats, it plays a negative role in the adaptation to hypoxia, because the inhibition of HIF-3α expression leads to an increase in physical endurance.

Clinical significance

DNA methylation in the introns of HIF3A is associated with BMI an adiposity.

See also

• Hypoxia inducible factors

Further reading

• Gu YZ, Moran SM, Hogenesch JB, Wartman L, Bradfield CA (1998). "Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha". Gene Expr. 7 (3): 205–13. PMC 6151950. PMID 9840812.
• Makino Y, Kanopka A, Wilson WJ, Tanaka H, Poellinger L (2002). "Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus". J. Biol. Chem. 277 (36): 32405–8. doi:10.1074/jbc.C200328200. PMID 12119283.
• Maynard MA, Qi H, Chung J, Lee EH, Kondo Y, Hara S, Conaway RC, Conaway JW, Ohh M (2003). "Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex". J. Biol. Chem. 278 (13): 11032–40. doi:10.1074/jbc.M208681200. PMID 12538644.
• Maynard MA, Evans AJ, Hosomi T, Hara S, Jewett MA, Ohh M (2006). "Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma". FASEB J. 19 (11): 1396–406. doi:10.1096/fj.05-3788com. PMID 16126907. S2CID 86404533.
• Jang MS, Park JE, Lee JA, Park SG, Myung PK, Lee DH, Park BC, Cho S (2005). "Binding and regulation of hypoxia-inducible factor-1 by the inhibitory PAS proteins". Biochem. Biophys. Res. Commun. 337 (1): 209–15. doi:10.1016/j.bbrc.2005.09.038. PMID 16182248.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Li QF, Wang XR, Yang YW, Lin H (2006). "Hypoxia upregulates hypoxia inducible factor (HIF)-3alpha expression in lung epithelial cells: characterization and comparison with HIF-1alpha". Cell Res. 16 (6): 548–58. doi:10.1038/sj.cr.7310072. PMID 16775626.
• Kollers S, Musilova P, Rubes J, Rocha D (2007). "Comparative mapping reveals multiple rearrangements between pig chromosome 6 and human 19q13". Anim. Genet. 37 (6): 595–6. doi:10.1111/j.1365-2052.2006.01516.x. PMID 17121608.