EPAS1

EPAS1
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1P97、2A24、3F1N、3F1O、3F1P、3H7W、3H82、4GHI、4GS9、4PKY、4XT2
识别号
别名	EPAS1；, ECYT4, HIF2A, HLF, MOP2, PASD2, bHLHe73, endothelial PAS domain protein 1, Hypoxia-inducible factor-2alpha
外部ID	OMIM：603349 MGI：109169 HomoloGene：1095 GeneCards：EPAS1
相关疾病
	肾细胞肿瘤
基因位置（人类）
染色体	2号染色体
终止	46,386,697 bp
基因位置（小鼠）
染色体	小鼠17号染色体
终止	87,140,838 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• DNA结合; • sequence-specific DNA binding; • protein dimerization activity; • DNA结合转录因子活性; • DNA-binding transcription activator activity, RNA polymerase II-specific; • 转录因子结合; • 血浆蛋白结合; • histone acetyltransferase binding; • protein heterodimerization activity; • DNA-binding transcription factor activity, RNA polymerase II-specific;
细胞组分	• 细胞质; • 细胞质基质; • nuclear speck; • 转录调节复合物; • 核质; • 细胞核;
生物学过程	• surfactant homeostasis; • 细胞分化; • response to hypoxia; • regulation of transcription, DNA-templated; • regulation of transcription from RNA polymerase II promoter in response to oxidative stress; • lung development; • norepinephrine metabolic process; • iron ion homeostasis; • mitochondrion organization; • embryonic placenta development; • cell maturation; • response to oxidative stress; • transcription, DNA-templated; • regulation of heart rate; • multicellular organism development; • blood vessel remodeling; • myoblast fate commitment; • 血管新生; • regulation of transcription from RNA polymerase II promoter in response to hypoxia; • erythrocyte differentiation; • 信号转导; • 视觉; • positive regulation of transcription by RNA polymerase II; • cellular response to hypoxia; • transcription by RNA polymerase II; • 翻译后修饰; • 造血作用; • regulation of transcription by RNA polymerase II; • positive regulation of cold-induced thermogenesis; • protein ubiquitination;
	Sources:Amigo / QuickGO
直系同源
	2034
	13819
	ENSG00000116016
	ENSMUSG00000024140
	Q99814
	P97481
	NM_001430
	NM_010137
	NP_001421
	NP_034267
	维基数据
查看/编辑人类	查看/编辑小鼠

内皮PAS结构域包含蛋白-1（英语：Endothelial PAS domain-containing protein 1，缩写EPAS1，也被称为缺氧诱导因子-2α亚基，英语：Hypoxia-inducible factor-2alpha，缩写HIF-2α）是一种由人类基因 EPAS1 所编码的蛋白质^[6]^[7]^[8]^[9]。

功能

EPAS1所表达的蛋白是一个转录因子的组成部分，该转录因子介导一些受氧气调控基因的表达，特别是低氧（缺氧）环境下。该蛋白包含一个碱性螺旋-环-螺旋蛋白二聚化结构域，此结构域也常见于其它氧应激相关信号通路蛋白。EPAS1涉及胚胎心脏（英语：embryonic heart）的发育，并在脐带的血管壁内皮细胞中表达。EPAS1维持儿茶酚胺类物质在胚胎早期发育中的稳定，以防止心脏衰竭^[9]。儿茶酚胺类物质包括肾上腺素和去甲肾上腺素，其稳定对胎儿与成人的心脏的健康有着重要作用^[10]。

交互作用

EPAS1能与芳香烃受体核转位子（英语：Aryl hydrocarbon receptor nuclear translocator）^[7]和ARNTL^[11]发生交互作用。

参考

人类的高海拔适应（英语：High-altitude adaptation in humans）
丹尼索瓦人

注释

^ 與EPAS1相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000116016 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000024140 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Tian H, McKnight SL, Russell DW. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. Feb 1997, 11 (1): 72–82. PMID 9000051. doi:10.1101/gad.11.1.72.
^ ^7.0 ^7.1 Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA. Characterization of a subset of the basic helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem. May 1997, 272 (13): 8581–93. PMID 9079689. doi:10.1074/jbc.272.13.8581.
^ Percy MJ, Beer PA, Campbell G, Dekker AW, Green AR, Oscier D, Rainey MG, van Wijk R, Wood M, Lappin TR, McMullin MF, Lee FS. Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. Blood. May 2008, 111 (11): 5400–2. PMC 2396730  . PMID 18378852. doi:10.1182/blood-2008-02-137703.
^ ^9.0 ^9.1 Entrez Gene: EPAS1 endothelial PAS domain protein 1. （原始内容存档于2019-10-16）.
^ Tian H, Hammer RE, Matsumoto AM, Russell DW, McKnight SL. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev. November 1998, 12 (21): 3320–4. PMC 317225  . PMID 9808618. doi:10.1101/gad.12.21.3320.
^ Hogenesch JB, Gu YZ, Jain S, Bradfield CA. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc. Natl. Acad. Sci. U.S.A. May 1998, 95 (10): 5474–9. PMC 20401  . PMID 9576906. doi:10.1073/pnas.95.10.5474.

参考文献

EPAS1引用了美国国家医学图书馆提供的数据，这些数据属于公共领域。

延伸阅读

Brahimi-Horn MC, Pouysségur J. The hypoxia-inducible factor and tumor progression along the angiogenic pathway.. Int. Rev. Cytol. 2005, 242: 157–213. PMID 15598469. doi:10.1016/S0074-7696(04)42004-X.
Haase VH. Hypoxia-inducible factors in the kidney.. Am. J. Physiol. Renal Physiol. 2006, 291 (2): F271–81. PMID 16554418. doi:10.1152/ajprenal.00071.2006.
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA. A "double adaptor" method for improved shotgun library construction.. Anal. Biochem. 1996, 236 (1): 107–13. PMID 8619474. doi:10.1006/abio.1996.0138.
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA. Large-scale concatenation cDNA sequencing.. Genome Res. 1997, 7 (4): 353–8. PMC 139146  . PMID 9110174. doi:10.1101/gr.7.4.353.
Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y. 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. 1997, 94 (9): 4273–8. PMC 20712  . PMID 9113979. doi:10.1073/pnas.94.9.4273.
Hogenesch JB, Gu YZ, Jain S, Bradfield CA. The basic helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors.. Proc. Natl. Acad. Sci. U.S.A. 1998, 95 (10): 5474–9. PMC 20401  . PMID 9576906. doi:10.1073/pnas.95.10.5474.
Takahata S, Sogawa K, Kobayashi A, Ema M, Mimura J, Ozaki N, Fujii-Kuriyama Y. Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock.. Biochem. Biophys. Res. Commun. 1998, 248 (3): 789–94. PMID 9704006. doi:10.1006/bbrc.1998.9012.
Ema M, Hirota K, Mimura J, Abe H, Yodoi J, Sogawa K, Poellinger L, Fujii-Kuriyama Y. 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. 1999, 18 (7): 1905–14. PMC 1171276  . PMID 10202154. doi:10.1093/emboj/18.7.1905.
Cockman ME, Masson N, Mole DR, Jaakkola P, Chang GW, Clifford SC, Maher ER, Pugh CW, Ratcliffe PJ, Maxwell PH. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein.. J. Biol. Chem. 2000, 275 (33): 25733–41. PMID 10823831. doi:10.1074/jbc.M002740200.
Maemura K, de la Monte SM, Chin MT, Layne MD, Hsieh CM, Yet SF, Perrella MA, Lee ME. CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.. J. Biol. Chem. 2001, 275 (47): 36847–51. PMID 11018023. doi:10.1074/jbc.C000629200.
Luo JC, Shibuya M. A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors (1alpha, 2alpha and 3alpha).. Oncogene. 2001, 20 (12): 1435–44. PMID 11313887. doi:10.1038/sj.onc.1204228.
Woods SL, Whitelaw ML. 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. 2002, 277 (12): 10236–43. PMID 11782478. doi:10.1074/jbc.M110752200.
Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.. Science. 2002, 295 (5556): 858–61. PMID 11823643. doi:10.1126/science.1068592.
Mole DR, Pugh CW, Ratcliffe PJ, Maxwell PH. 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. 2002, 42: 333–47. PMID 12123724. doi:10.1016/S0065-2571(01)00037-1.
Sivridis E, Giatromanolaki A, Gatter KC, Harris AL, Koukourakis MI. Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma.. Cancer. 2002, 95 (5): 1055–63. PMID 12209691. doi:10.1002/cncr.10774.
Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, Rauter M, Plate K, Sieweke M, Breier G, Flamme I. 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. 2003, 278 (9): 7520–30. PMID 12464608. doi:10.1074/jbc.M211298200.
Sang N, Stiehl DP, Bohensky J, Leshchinsky I, Srinivas V, Caro J. MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300.. J. Biol. Chem. 2003, 278 (16): 14013–9. PMID 12588875. doi:10.1074/jbc.M209702200.

外部链接

医学主题词表（MeSH）：EPAS1+protein,+human

[1] 與EPAS1相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000116016 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000024140 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9000051-6] Tian H, McKnight SL, Russell DW. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. Feb 1997, 11 (1): 72–82. PMID 9000051. doi:10.1101/gad.11.1.72.

[pmid9079689-7] 7.0 ^7.1 Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA. Characterization of a subset of the basic helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem. May 1997, 272 (13): 8581–93. PMID 9079689. doi:10.1074/jbc.272.13.8581.

[pmid18378852-8] Percy MJ, Beer PA, Campbell G, Dekker AW, Green AR, Oscier D, Rainey MG, van Wijk R, Wood M, Lappin TR, McMullin MF, Lee FS. Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. Blood. May 2008, 111 (11): 5400–2. PMC 2396730  . PMID 18378852. doi:10.1182/blood-2008-02-137703.

[entrez-9] 9.0 ^9.1 Entrez Gene: EPAS1 endothelial PAS domain protein 1. （原始内容存档于2019-10-16）.

[pmid9808618-10] Tian H, Hammer RE, Matsumoto AM, Russell DW, McKnight SL. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev. November 1998, 12 (21): 3320–4. PMC 317225  . PMID 9808618. doi:10.1101/gad.12.21.3320.

[pmid9576906-11] Hogenesch JB, Gu YZ, Jain S, Bradfield CA. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc. Natl. Acad. Sci. U.S.A. May 1998, 95 (10): 5474–9. PMC 20401  . PMID 9576906. doi:10.1073/pnas.95.10.5474.

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