ATOX1
Copper transport protein ATOX1 is a protein that in humans is encoded by the ATOX1 gene.[1][2]
This gene encodes a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network for later incorporation to the ceruloplasmin. This protein also functions as an antioxidant against superoxide and hydrogen peroxide, and therefore, may play a significant role in cancer carcinogenesis. Because of its cytogenetic location, this gene represents a candidate gene for 5q-syndrome.[2]
In melanocytic cells ATOX1 gene expression may be regulated by MITF[3].
Interactions
ATOX1 has been shown to interact with Wilson disease protein[4][5] and ATP7A.[4]
References
- ^ Klomp LW, Lin SJ, Yuan DS, Klausner RD, Culotta VC, Gitlin JD (May 1997). "Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis". J Biol Chem 272 (14): 9221–6. doi:10.1074/jbc.272.14.9221. PMID 9083055.
- ^ a b "Entrez Gene: ATOX1 ATX1 antioxidant protein 1 homolog (yeast)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=475.
- ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ^ a b Larin, D; Mekios C, Das K, Ross B, Yang A S, Gilliam T C (Oct. 1999). "Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p". J. Biol. Chem. (UNITED STATES) 274 (40): 28497–504. doi:10.1074/jbc.274.40.28497. ISSN 0021-9258. PMID 10497213.
- ^ Hamza, I; Schaefer M, Klomp L W, Gitlin J D (Nov. 1999). "Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (23): 13363–8. doi:10.1073/pnas.96.23.13363. ISSN 0027-8424. PMC 23953. PMID 10557326. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23953.
Further reading
- Hung IH, Casareno RL, Labesse G, et al. (1998). "HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense.". J. Biol. Chem. 273 (3): 1749–54. doi:10.1074/jbc.273.3.1749. PMID 9430722.
- Larin D, Mekios C, Das K, et al. (1999). "Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p.". J. Biol. Chem. 274 (40): 28497–504. doi:10.1074/jbc.274.40.28497. PMID 10497213.
- Hamza I, Schaefer M, Klomp LW, Gitlin JD (1999). "Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis.". Proc. Natl. Acad. Sci. U.S.A. 96 (23): 13363–8. doi:10.1073/pnas.96.23.13363. PMC 23953. PMID 10557326. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23953.
- Wernimont AK, Huffman DL, Lamb AL, et al. (2000). "Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins.". Nat. Struct. Biol. 7 (9): 766–71. doi:10.1038/78999. PMID 10966647.
- Boultwood J, Strickson AJ, Jabs EW, et al. (2000). "Physical mapping of the human ATX1 homologue (HAH1) to the critical region of the 5q- syndrome within 5q32, and immediately adjacent to the SPARC gene.". Hum. Genet. 106 (1): 127–9. PMID 10982193.
- Walker JM, Tsivkovskii R, Lutsenko S (2002). "Metallochaperone Atox1 transfers copper to the NH2-terminal domain of the Wilson's disease protein and regulates its catalytic activity.". J. Biol. Chem. 277 (31): 27953–9. doi:10.1074/jbc.M203845200. PMID 12029094.
- Moore SD, Helmle KE, Prat LM, Cox DW (2003). "Tissue localization of the copper chaperone ATOX1 and its potential role in disease.". Mamm. Genome 13 (10): 563–8. doi:10.1007/s00335-002-2172-9. PMID 12420134.
- 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.
- Liu PC, Koeller DM, Kaler SG (2004). "Genomic organization of ATOX1, a human copper chaperone.". BMC Genet. 4: 4. doi:10.1186/1471-2156-4-4. PMC 150598. PMID 12594858. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=150598.
- Strausak D, Howie MK, Firth SD, et al. (2003). "Kinetic analysis of the interaction of the copper chaperone Atox1 with the metal binding sites of the Menkes protein.". J. Biol. Chem. 278 (23): 20821–7. doi:10.1074/jbc.M212437200. PMID 12679332.
- Ralle M, Lutsenko S, Blackburn NJ (2003). "X-ray absorption spectroscopy of the copper chaperone HAH1 reveals a linear two-coordinate Cu(I) center capable of adduct formation with exogenous thiols and phosphines.". J. Biol. Chem. 278 (25): 23163–70. doi:10.1074/jbc.M303474200. PMID 12686548.
- Lutsenko S, Tsivkovskii R, Walker JM (2003). "Functional properties of the human copper-transporting ATPase ATP7B (the Wilson's disease protein) and regulation by metallochaperone Atox1.". Ann. N. Y. Acad. Sci. 986: 204–11. doi:10.1111/j.1749-6632.2003.tb07161.x. PMID 12763797.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Wernimont AK, Yatsunyk LA, Rosenzweig AC (2004). "Binding of copper(I) by the Wilson disease protein and its copper chaperone.". J. Biol. Chem. 279 (13): 12269–76. doi:10.1074/jbc.M311213200. PMID 14709553.
- Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
- Anastassopoulou I, Banci L, Bertini I, et al. (2004). "Solution structure of the apo and copper(I)-loaded human metallochaperone HAH1.". Biochemistry 43 (41): 13046–53. doi:10.1021/bi0487591. PMID 15476398.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Banci L, Bertini I, Ciofi-Baffoni S, et al. (2005). "An NMR study of the interaction between the human copper(I) chaperone and the second and fifth metal-binding domains of the Menkes protein.". FEBS J. 272 (3): 865–71. doi:10.1111/j.1742-4658.2004.04526.x. PMID 15670166.
- Jeney V, Itoh S, Wendt M, et al. (2005). "Role of antioxidant-1 in extracellular superoxide dismutase function and expression.". Circ. Res. 96 (7): 723–9. doi:10.1161/01.RES.0000162001.57896.66. PMID 15761197.
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PDB gallery
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1fe0: CRYSTAL STRUCTURE OF CADMIUM-HAH1
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1fe4: CRYSTAL STRUCTURE OF MERCURY-HAH1
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1fee: CRYSTAL STRUCTURE OF COPPER-HAH1
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1tl4: Solution structure of Cu(I) HAH1
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1tl5: Solution structure of apoHAH1
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