Difference between revisions of "YPL170W"

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'''Description of YPL170W:''' Heme-binding protein involved in regulation of cytochrome P450 protein Erg11p; damage response protein, related to mammalian membrane progesterone receptors; mutations lead to defects in telomeres, mitochondria, and sterol synthesis<ref name='S000080892'>Mallory JC, et al. (2005) Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae. Mol Cell Biol 25(5):1669-79 {{SGDpaper|S000080892}} PMID 15713626</ref><ref name='S000072913'>Hand RA, et al. (2003) Saccharomyces cerevisiae Dap1p, a novel DNA damage response protein related to the mammalian membrane-associated progesterone receptor. Eukaryot Cell 2(2):306-17
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'''Description of YPL170W:''' Heme-binding protein involved in regulation of cytochrome P450 protein Erg11p; damage response protein, related to mammalian membrane progesterone receptors; mutations lead to defects in telomeres, mitochondria, and sterol synthesis<ref name='S000072913'>Hand RA, et al. (2003) Saccharomyces cerevisiae Dap1p, a novel DNA damage response protein related to the mammalian membrane-associated progesterone receptor. Eukaryot Cell 2(2):306-17 {{SGDpaper|S000072913}} PMID 12684380</ref><ref name='S000080892'>Mallory JC, et al. (2005) Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae. Mol Cell Biol 25(5):1669-79
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  {{SGDpaper|S000080892}} PMID 15713626</ref>
 
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Revision as of 14:05, 25 February 2010

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Systematic name YPL170W
Gene name DAP1
Aliases
Feature type ORF, Verified
Coordinates Chr XVI:228313..228771
Primary SGDID S000006091


Description of YPL170W: Heme-binding protein involved in regulation of cytochrome P450 protein Erg11p; damage response protein, related to mammalian membrane progesterone receptors; mutations lead to defects in telomeres, mitochondria, and sterol synthesis[1][2]




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Community Commentary

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Dap1p is part of a widely conserved family of proteins that are structurally related to cytochrome b5. Dap1p is associated with damage resistance because cells lacking Dap1p are hyper-sensitive to the DNA damaging agent methyl methanesulfonate, and this function is conserved with its human homologue. Dap1p and its mouse, Schizosaccharomyces pombe, and human homologues bind to heme, requiring highly conserved sequences in a region of the protein called the heme-1 domain. Dap1p binds to heme in a five-coordinate ferric state via a conserved tyrosine Y138 residue, while cytochrome b5 binds in a six-coordinate state via histidines. Dap1p functions by activating a cytochrome P450 protein called Erg11p (also called lanosterol demethylase or Cyp51p), which catalyzes a critical step of ergosterol synthesis. Erg11p is the target of the azole antifungal drugs, such as ketoconazole, fluconazole and miconazole, and Dap1p regulates the susceptibility of yeast cells to these drugs. Dap1p also activates Erg3p/ sterol C-5 desaturase, which is a proposed iron-binding protein, and Dap1p contributes to the uptake and intracellular transport of iron. The human homologue, called Hpr6 (human progesterone receptor/heme-1 domain protein) or PGRMC1 (progesterone receptor membrane component 1), is over-expressed in some types of human tumors and regulates damage sensitivity and sterol synthesis, suggesting conserved functions between the yeast and human homologues.




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References

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  1. Hand RA, et al. (2003) Saccharomyces cerevisiae Dap1p, a novel DNA damage response protein related to the mammalian membrane-associated progesterone receptor. Eukaryot Cell 2(2):306-17 SGD PMID 12684380
  2. Mallory JC, et al. (2005) Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae. Mol Cell Biol 25(5):1669-79 SGD PMID 15713626

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References

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