EPAS1

內皮PAS結構域包含蛋白-1（英語：Endothelial PAS domain-containing protein 1，縮寫EPAS1，也被稱為缺氧誘導因子-2α亞基，英語：Hypoxia-inducible factor-2alpha，縮寫HIF-2α）是一種由人類基因 EPAS1 所編碼的蛋白質^[6][7][8][9]。

EPAS1
已知的結構 PDB 直系同源搜尋: PDBe RCSB PDBID列表 1P97、​2A24、​3F1N、​3F1O、​3F1P、​3H7W、​3H82、​4GHI、​4GS9、​4PKY、​4XT2
識別號
別名	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
相關疾病
腎細胞腫瘤[1]
基因位置（人類） 染色體 2號染色體[2] 基因座 2p21 起始 46,293,667 bp[2] 終止 46,386,697 bp[2]
基因位置（小鼠） 染色體 小鼠17號染色體[3] 基因座 17|17 E4 起始 87,061,128 bp[3] 終止 87,140,838 bp[3]
RNA表達模式
查閱更多表達數據
基因本體 分子功能 • DNA結合 • sequence-specific DNA binding • protein dimerization activity • DNA結合轉錄因子活性 • DNA-binding transcription activator activity, RNA polymerase II-specific • 轉錄因子結合 • 血漿蛋白結合 • histone acetyltransferase binding • protein heterodimerization activity • DNA-binding transcription factor activity, RNA polymerase II-specific 細胞組分 • 細胞質 • 細胞質基質 • nuclear speck • 轉錄調節複合物 • 核質 • 細胞核 生物學過程 • surfactant homeostasis • 細胞分化 • 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 • 信號轉導 • 視覺 • positive regulation of transcription by RNA polymerase II • cellular response to hypoxia • transcription by RNA polymerase II • 轉譯後修飾 • 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
物種	人類	小鼠
Entrez	2034	13819
Ensembl	ENSG00000116016	ENSMUSG00000024140
UniProt	Q99814	P97481
mRNA​序列	​NM_001430	NM_010137
蛋白序列	NP_001421	NP_034267
基因位置​（UCSC）	Chr 2: 46.29 – 46.39 Mb	Chr 17: 87.06 – 87.14 Mb
PubMed​查找	[4]	[5]
維基數據
檢視/編輯人類 檢視/編輯小鼠

功能

EPAS1所表達的蛋白是一個轉錄因子的組成部分，該轉錄因子介導一些受氧氣調控基因的表達，特別是低氧（缺氧）環境下。該蛋白包含一個鹼性螺旋-環-螺旋蛋白二聚化結構域，此結構域也常見於其它氧應激相關信號通路蛋白。EPAS1涉及胚胎心臟（英語：embryonic heart）的發育，並在臍帶的血管壁內皮細胞中表達。EPAS1維持兒茶酚胺類物質在胚胎早期發育中的穩定，以防止心臟衰竭^[9]。兒茶酚胺類物質包括腎上腺素和去甲腎上腺素，其穩定對胎兒與成人的心臟的健康有着重要作用^[10]。

交互作用

EPAS1能與芳香烴受體核轉位子（英語：Aryl hydrocarbon receptor nuclear translocator）^[7]和ARNTL^[11]發生交互作用。

參考

• 人類的高海拔適應（英語：High-altitude adaptation in humans）
• 丹尼索瓦人

註釋

1. 與EPAS1相關的疾病；在維基數據上查看/編輯參考.
2. GRCh38: Ensembl release 89: ENSG00000116016 - Ensembl, May 2017
3. 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.
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.
7. 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.
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.
9. Entrez Gene: EPAS1 endothelial PAS domain protein 1. （原始內容存檔於2019-10-16）.
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.
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.

參考文獻

EPAS1引用了美國國家醫學圖書館提供的數據，這些數據屬於公共領域。

延伸閱讀

• 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.

外部連結

• 醫學主題詞表（MeSH）：EPAS1+protein,+human