Structure, expression, and chromosomal localization of the mouse Atox1 gene

被引:13
作者
Hamza, I
Klomp, LWJ
Gaedigk, R
White, RA
Gitlin, JD
机构
[1] Washington Univ, Sch Med, Edward Mallinckrodt Dept Pediat, St Louis, MO 63110 USA
[2] Childrens Mercy Hosp, Sect Med Genet & Mol Med, Kansas City, MO 64108 USA
关键词
D O I
10.1006/geno.1999.6046
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Copper trafficking in eukaryotes involves small proteins termed metallochaperones, which mediate copper delivery to specific intracellular sites, Previous studies in yeast and human cell lines have suggested that Atox1 plays a critical role in copper delivery to the secretory pathway. In the present study, a mouse Atox1 (mAtox1) cDNA was cloned and shown to encode an open reading frame with 85% amino acid identity to human Atox1. RNA blot analysis revealed that mAtox1 was expressed as a single transcript in multiple tissues, and immunoblotting indicated that the relative abundance of mAtox1 mRNA directly correlated with mAtox1 protein. Analysis of the mAtox1 gene locus revealed a genomic structure with four exons encompassing a total of 14.5 kb, RFLP and haplotype analyses indicated that the mAtox1 locus was tightly linked to the Trhr and D15Bir7 loci on mouse chromosome 15, Taken together, these data reveal marked evolutionary conservation of Atox1 structure and provide a genomic organization and localization that will aid in the genetic deciphering of the molecular role of this protein in copper homeostasis. (C) 2000 Academic Press.
引用
收藏
页码:294 / 297
页数:4
相关论文
共 14 条
  • [1] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
    Altschul, SF
    Madden, TL
    Schaffer, AA
    Zhang, JH
    Zhang, Z
    Miller, W
    Lipman, DJ
    [J]. NUCLEIC ACIDS RESEARCH, 1997, 25 (17) : 3389 - 3402
  • [2] Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis
    Hamza, I
    Schaefer, M
    Klomp, LWJ
    Gitlin, JD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (23) : 13363 - 13368
  • [3] Harris Z. Leah, 1996, American Journal of Clinical Nutrition, V63, p836S
  • [4] HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense
    Hung, IH
    Casareno, RLB
    Labesse, G
    Mathews, FS
    Gitlin, JD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (03) : 1749 - 1754
  • [5] Klomp LWJ, 1997, J BIOL CHEM, V272, P9221, DOI 10.1074/jbc.272.14.9221
  • [6] Lin SJ, 1997, J BIOL CHEM, V272, P9215
  • [7] Expression of copper trafficking genes in the mouse brain
    Nishihara, E
    Furuyama, T
    Yamashita, S
    Mori, N
    [J]. NEUROREPORT, 1998, 9 (14) : 3259 - 3263
  • [8] A delicate balance:: Homeostatic control of copper uptake and distribution
    Peña, MMO
    Lee, J
    Thiele, DJ
    [J]. JOURNAL OF NUTRITION, 1999, 129 (07) : 1251 - 1260
  • [9] Structure-function analyses of the ATX1 metallochaperone
    Portnoy, ME
    Rosenzweig, AC
    Rae, T
    Huffman, DL
    O'Halloran, TV
    Culotta, VC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (21) : 15041 - 15045
  • [10] Metal ion chaperone function of the soluble Cu(I) receptor Atx1
    Pufahl, RA
    Singer, CP
    Peariso, KL
    Lin, SJ
    Schmidt, PJ
    Fahrni, CJ
    Culotta, VC
    PennerHahn, JE
    OHalloran, TV
    [J]. SCIENCE, 1997, 278 (5339) : 853 - 856