Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Epas1. (This text reflects annotations as of Tuesday, May 21, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of August 1, 2007. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Epas1
  • participates in the following biological processes:
    • positive regulation of transcription from RNA polymerase II promoter ^{[6, 9]}
    • regulation of transcription from RNA polymerase II promoter in response to oxidative stress ^[14]
  • performs the following molecular functions:
    • DNA binding ^{[6, 12]}
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription ^[1]
    • sequence-specific DNA binding transcription factor activity ^[6]
  • is located in the following cellular components:
    • cytoplasm ^[10]
    • nucleus ^[6]
    • transcription factor complex ^[6]
• Researchers have inferred, based on physical interactions, that the gene product of Epas1
  • performs the following molecular functions:
    • protein heterodimerization activity ^[7]
    • transcription factor binding ^[6]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Epas1
  • participates in the following biological processes:
    • angiogenesis ^{[2, 4, 5]}
    • blood vessel remodeling ^[11]
    • cell maturation ^[2]
    • erythrocyte differentiation ^[8]
    • hemopoiesis ^{[15, 16]}
    • lung development ^[2]
    • mitochondrion organization ^[14]
    • myoblast fate commitment ^[13]
    • norepinephrine metabolic process ^[17]
    • positive regulation of transcription from RNA polymerase II promoter ^[12]
    • regulation of heart rate ^[17]
    • regulation of transcription from RNA polymerase II promoter in response to oxidative stress ^[8]
    • response to hypoxia ^[16]
    • response to oxidative stress ^[14]
    • surfactant homeostasis ^[2]
    • visual perception ^[4]
• Researchers have inferred, based on genetic interactions, that the gene product of Epas1
  • participates in the following biological processes:
    • cell differentiation based on interactions with Hif1a ^[3]
    • embryonic placenta development based on interactions with Hif1a ^[3]
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Arnt, Ets1 ^{[6, 7]}
    • response to oxidative stress based on interactions with Sod2 ^[9]
  • performs the following molecular functions:
    • DNA binding based on interactions with Arnt ^[7]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Epas1:
  • participates in the following biological processes:
    • positive regulation of transcription from RNA polymerase II promoter
    • response to hypoxia
  • performs the following molecular functions:
    • DNA binding
    • histone acetyltransferase binding
    • protein heterodimerization activity
    • sequence-specific DNA binding
    • sequence-specific DNA binding transcription factor activity
    • transcription factor binding
  • is located in the following cellular components:
    • cytoplasm
    • nucleus
    • transcription factor complex

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Summary text based on GO annotations supported by structural data

• Epas1 encodes a protein or proteins that contain the following InterPro domains: HIF-1 alpha, transactivation domain, C-terminal, Hypoxia-inducible factor, alpha subunit, Myc-type, basic helix-loop-helix (bHLH) domain, Nuclear translocator, PAC motif, PAS domain, PAS fold, PAS fold-3, indicating that the gene product:
  • participates in the following biological processes:
    • regulation of transcription, DNA-dependent
    • signal transduction
  • performs the following molecular functions:
    • protein dimerization activity
    • signal transducer activity

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Epas1 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
    • regulation of transcription, DNA-dependent
    • transcription, DNA-dependent

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References

1. An HJ et al. (2011) The survival effect of mitochondrial Higd-1a is associated with suppression of cytochrome C release and prevention of caspase activation. Biochim Biophys Acta, 1813:2088-98. (PubMed:21856340)
2. Compernolle V et al. (2002) Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med, 8:702-10. (PubMed:12053176)
3. Cowden Dahl KD et al. (2005) Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation. Mol Cell Biol, 25:10479-91. (PubMed:16287860)
4. Ding K et al. (2005) Retinal Disease in Mice Lacking Hypoxia-Inducible Transcription Factor-2{alpha}. Invest Ophthalmol Vis Sci, 46:1010-6. (PubMed:15728559)
5. Duan LJ et al. (2005) Endothelium-intrinsic requirement for Hif-2alpha during vascular development. Circulation, 111:2227-32. (PubMed:15851592)
6. Elvert G 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, 278:7520-30. (PubMed:12464608)
7. Ema M 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, 94:4273-8. (PubMed:9113979)
8. Gruber M et al. (2007) Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci U S A, 104:2301-6. (PubMed:17284606)
9. Oktay Y et al. (2007) Hypoxia-inducible factor 2alpha regulates expression of the mitochondrial aconitase chaperone protein frataxin. J Biol Chem, 282:11750-6. (PubMed:17322295)
10. Park SK et al. (2003) Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Mol Cell Biol, 23:4959-71. (PubMed:12832481)
11. Peng J et al. (2000) The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc Natl Acad Sci U S A, 97:8386-91. (PubMed:10880563)
12. Rankin EB et al. (2007) Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest, 117:1068-77. (PubMed:17404621)
13. Rasbach KA et al. (2010) PGC-1{alpha} regulates a HIF2{alpha}-dependent switch in skeletal muscle fiber types. Proc Natl Acad Sci U S A, null:null. (PubMed:21106753)
14. Scortegagna M et al. (2003) Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1-/- mice. Nat Genet, 35:331-40. (PubMed:14608355)
15. Scortegagna M et al. (2003) The HIF family member EPAS1/HIF-2alpha is required for normal hematopoiesis in mice. Blood, 102:1634-40. (PubMed:12750163)
16. Scortegagna M et al. (2005) HIF-2alpha regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood, 105:3133-40. (PubMed:15626745)
17. Tian H et al. (1998) The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev, 12:3320-4. (PubMed:9808618)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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