HIF3A

Hypoxia inducible factor 3, alpha subunit
Identifiers
Symbols	HIF3A ; HIF-3A; IPAS; MOP7; PASD7; bHLHe17
External IDs	OMIM: 609976 MGI: 1859778 HomoloGene: 9646 GeneCards: HIF3A Gene
Gene ontology Molecular function • RNA polymerase II transcription factor activity, sequence-specific DNA binding • DNA binding • transcription coactivator activity • transcription corepressor activity • protein dimerization activity Cellular component • nucleoplasm • mitochondrion • cytosol • nuclear speck Biological process • angiogenesis • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • apoptotic process • positive regulation of transcription from RNA polymerase II promoter • regulation of transcription from RNA polymerase II promoter in response to hypoxia • cellular response to hypoxia • negative regulation of nucleic acid-templated transcription Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	64344	53417
Ensembl	ENSG00000124440	ENSMUSG00000004328
UniProt	Q9Y2N7	Q0VBL6
RefSeq (mRNA)	NM_022462	NM_001162950
RefSeq (protein)	NP_071907	NP_001156422
Location (UCSC)	Chr 19: 46.3 – 46.34 Mb	Chr 7: 17.03 – 17.06 Mb
PubMed search

Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.^[1][2][3]

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.^[3]

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.^[4]

Clinical significance

DNA methylation in the introns of HIF3A is associated with BMI an adiposity.^[5]

See also

• Hypoxia inducible factors

References

1. Hara S, Hamada J, Kobayashi C, Kondo Y, Imura N (Sep 2001). "Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha". Biochem Biophys Res Commun 287 (4): 808–13. doi:10.1006/bbrc.2001.5659. PMID 11573933.
2. Makino Y, Cao R, Svensson K, Bertilsson G, Asman M, Tanaka H, Cao Y, Berkenstam A, Poellinger L (Dec 2001). "Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression". Nature 414 (6863): 550–4. doi:10.1038/35107085. PMID 11734856.
3. "Entrez Gene: HIF3A hypoxia inducible factor 3, alpha subunit".
4. Drevytska T, Gavenauskas B, Drozdovska S, Nosar V, Dosenko V, Mankovska I (2012). "HIF-3α mRNA expression changes in different tissues and their role in adaptation to intermittent hypoxia and physical exercise". Pathophysiology 19 (3): 205–14. doi:10.1016/j.pathophys.2012.06.002. PMID 22884965.
5. Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aïssi D, Wahl S, Meduri E, Morange PE, Gagnon F, Grallert H, Waldenberger M, Peters A, Erdmann J, Hengstenberg C, Cambien F, Goodall AH, Ouwehand WH, Schunkert H, Thompson JR, Spector TD, Gieger C, Trégouët DA, Deloukas P, Samani NJ (2014). "DNA methylation and body-mass index: a genome-wide analysis.". Lancet 383 (9933): 1990–1998. doi:10.1016/S0140-6736(13)62674-4. PMID 24630777.

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. 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.
• 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.