EPAS1

Endothelial PAS domain protein 1
PDB rendering based on 1p97.
Available structures PDB 1P97, 2A24, 3F1N, 3F1O, 3F1P, 3H7W, 3H82
Identifiers
Symbols	EPAS1; ECYT4; HIF2A; HLF; MOP2; PASD2; bHLHe73
External IDs	OMIM: 603349 MGI: 109169 HomoloGene: 1095 GeneCards: EPAS1 Gene
Gene Ontology Molecular function • DNA binding • sequence-specific DNA binding transcription factor activity • sequence-specific enhancer binding RNA polymerase II transcription factor activity • transcription coactivator activity • signal transducer activity • protein binding • transcription factor binding • histone acetyltransferase binding • sequence-specific DNA binding • protein heterodimerization activity Cellular component • nucleus • transcription factor complex • transcription factor complex • cytoplasm Biological process • angiogenesis • response to hypoxia • transcription from RNA polymerase II promoter • signal transduction • multicellular organismal development • cell differentiation • positive regulation of transcription from RNA polymerase II promoter • myoblast cell fate commitment Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2034	13819
Ensembl	ENSG00000116016	ENSMUSG00000024140
UniProt	Q99814	Q6PEU2
RefSeq (mRNA)	NM_001430	NM_010137.3
RefSeq (protein)	NP_001421	NP_034267.3
Location (UCSC)	Chr 2: 46.52 – 46.61 Mb	Chr 17: 87.15 – 87.23 Mb
PubMed search	[1]	[2]

Endothelial PAS domain-containing protein 1 is a protein that in humans is encoded by the EPAS1 gene.

Function

This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels.

Clinical significance

Mutations in this gene are associated with erythrocytosis familial type 4 and pulmonary hypertension. There is also evidence that certain variants of this gene provide protection for people living at high altitude.

Interactions

EPAS1 has been shown to interact with Aryl hydrocarbon receptor nuclear translocator and ARNTL.

Further reading

• Brahimi-Horn MC, Pouysségur J (2005). "The hypoxia-inducible factor and tumor progression along the angiogenic pathway.". Int. Rev. Cytol. 242: 157–213. doi:10.1016/S0074-7696(04)42004-X. PMID 15598469. 
• Haase VH (2006). "Hypoxia-inducible factors in the kidney.". Am. J. Physiol. Renal Physiol. 291 (2): F271–81. doi:10.1152/ajprenal.00071.2006. PMID 16554418. 
• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139146. 
• Ema M, Taya S, Yokotani N, et al. (1997). "A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development.". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4273–8. doi:10.1073/pnas.94.9.4273. PMC 20712. PMID 9113979. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20712. 
• Hogenesch JB, Gu YZ, Jain S, Bradfield CA (1998). "The basic helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors.". Proc. Natl. Acad. Sci. U.S.A. 95 (10): 5474–9. doi:10.1073/pnas.95.10.5474. PMC 20401. PMID 9576906. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20401. 
• Takahata S, Sogawa K, Kobayashi A, et al. (1998). "Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock.". Biochem. Biophys. Res. Commun. 248 (3): 789–94. doi:10.1006/bbrc.1998.9012. PMID 9704006. 
• Ema M, Hirota K, Mimura J, et al. (1999). "Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300.". EMBO J. 18 (7): 1905–14. doi:10.1093/emboj/18.7.1905. PMC 1171276. PMID 10202154. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171276. 
• Cockman ME, Masson N, Mole DR, et al. (2000). "Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein.". J. Biol. Chem. 275 (33): 25733–41. doi:10.1074/jbc.M002740200. PMID 10823831. 
• Maemura K, de la Monte SM, Chin MT, et al. (2001). "CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.". J. Biol. Chem. 275 (47): 36847–51. doi:10.1074/jbc.C000629200. PMID 11018023. 
• Luo JC, Shibuya M (2001). "A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors (1alpha, 2alpha and 3alpha).". Oncogene 20 (12): 1435–44. doi:10.1038/sj.onc.1204228. PMID 11313887. 
• Woods SL, Whitelaw ML (2002). "Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors.". J. Biol. Chem. 277 (12): 10236–43. doi:10.1074/jbc.M110752200. PMID 11782478. 
• Lando D, Peet DJ, Whelan DA, et al. (2002). "Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.". Science 295 (5556): 858–61. doi:10.1126/science.1068592. PMID 11823643. 
• Mole DR, Pugh CW, Ratcliffe PJ, Maxwell PH (2002). "Regulation of the HIF pathway: enzymatic hydroxylation of a conserved prolyl residue in hypoxia-inducible factor alpha subunits governs capture by the pVHL E3 ubiquitin ligase complex.". Adv. Enzyme Regul. 42: 333–47. doi:10.1016/S0065-2571(01)00037-1. PMID 12123724. 
• Sivridis E, Giatromanolaki A, Gatter KC, et al. (2002). "Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma.". Cancer 95 (5): 1055–63. doi:10.1002/cncr.10774. PMID 12209691. 
• Elvert G, Kappel A, Heidenreich R, et al. (2003). "Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1).". J. Biol. Chem. 278 (9): 7520–30. doi:10.1074/jbc.M211298200. PMID 12464608. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Sang N, Stiehl DP, Bohensky J, et al. (2003). "MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300.". J. Biol. Chem. 278 (16): 14013–9. doi:10.1074/jbc.M209702200. PMID 12588875. 

External links

• MeSH EPAS1+protein,+human

This article incorporates text from the United States National Library of Medicine, which is in the public domain.