Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1989 Aug;45(2):276–282.

Assignment of human genes for phosphorylase kinase subunits alpha (PHKA) to Xq12-q13 and beta (PHKB) to 16q12-q13.

U Francke 1, B T Darras 1, N F Zander 1, M W Kilimann 1
PMCID: PMC1683359  PMID: 2757032

Abstract

Phosphorylase kinase (PHK), the enzyme that activates glycogen phosphorylases in muscle, liver, and other tissues, is composed of four different subunits. Recently isolated rabbit muscle cDNAs for the larger two subunits, alpha and beta, have been used to map the location of their cognate sequences on human chromosomes. Southern blot analysis of rodent x human somatic cell hybrid panels, as well as in situ chromosomal hybridization, have provided evidence of single sites for both genes. The alpha subunit gene (PHKA) is located on the proximal long arm of the X chromosome in region Xq12-q13 near the locus for phosphoglycerate kinase (PGK1). X-linked mutations leading to PHK deficiency, known to exist in humans and mice, are likely to involve this locus. This hypothesis is consistent with the proximity of the Phk and Pgk-1 loci on the mouse X chromosome. In contrast, the beta subunit gene (PHKB) was found to be autosomal and was mapped to chromosome 16, region q12-q13 on the proximal long arm. Several different autosomally inherited forms of PHK deficiency for which the PHKB could be a candidate gene have been described in humans and rats.

Full text

PDF
276

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barton D. E., Arquint M., Roder J., Dunn R., Francke U. The myelin-associated glycoprotein gene: mapping to human chromosome 19 and mouse chromosome 7 and expression in quivering mice. Genomics. 1987 Oct;1(2):107–112. doi: 10.1016/0888-7543(87)90002-4. [DOI] [PubMed] [Google Scholar]
  2. Barton D. E., Yang-Feng T. L., Francke U. The human tyrosine aminotransferase gene mapped to the long arm of chromosome 16 (region 16q22----q24) by somatic cell hybrid analysis and in situ hybridization. Hum Genet. 1986 Mar;72(3):221–224. doi: 10.1007/BF00291881. [DOI] [PubMed] [Google Scholar]
  3. Bashan N., Iancu T. C., Lerner A., Fraser D., Potashnik R., Moses S. W. Glycogenosis due to liver and muscle phosphorylase kinase deficiency. Pediatr Res. 1981 Apr;15(4 Pt 1):299–303. doi: 10.1203/00006450-198104000-00002. [DOI] [PubMed] [Google Scholar]
  4. Brockdorff N., Fisher E. M., Orkin S. H., Lyon M. F., Brown S. D. Localization of the human X-linked gene for chronic granulomatous disease to the mouse X chromosome: implications for X-chromosome evolution. Cytogenet Cell Genet. 1988;48(2):124–125. doi: 10.1159/000132605. [DOI] [PubMed] [Google Scholar]
  5. Chamberlain J. S., VanTuinen P., Reeves A. A., Philip B. A., Caskey C. T. Isolation of cDNA clones for the catalytic gamma subunit of mouse muscle phosphorylase kinase: expression of mRNA in normal and mutant Phk mice. Proc Natl Acad Sci U S A. 1987 May;84(9):2886–2890. doi: 10.1073/pnas.84.9.2886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen P. T., Burchell A., Cohen P. The molecular basis of skeletal muscle phosphorylase kinase deficiency. Eur J Biochem. 1976 Jul 1;66(2):347–356. doi: 10.1111/j.1432-1033.1976.tb10524.x. [DOI] [PubMed] [Google Scholar]
  7. Coussens L., Parker P. J., Rhee L., Yang-Feng T. L., Chen E., Waterfield M. D., Francke U., Ullrich A. Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science. 1986 Aug 22;233(4766):859–866. doi: 10.1126/science.3755548. [DOI] [PubMed] [Google Scholar]
  8. Eicher E. M., Nesbitt M. N., Francke U. Cytological identification of the chromosomes involved in Searle's translocation and the location of the centromere in the X chromosome of the mouse. Genetics. 1972 Aug;71(4):643–648. doi: 10.1093/genetics/71.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eishi Y., Takemura T., Sone R., Yamamura H., Narisawa K., Ichinohasama R., Tanaka M., Hatakeyama S. Glycogen storage disease confined to the heart with deficient activity of cardiac phosphorylase kinase: a new type of glycogen storage disease. Hum Pathol. 1985 Feb;16(2):193–197. doi: 10.1016/s0046-8177(85)80071-x. [DOI] [PubMed] [Google Scholar]
  10. Francke U., Ochs H. D., de Martinville B., Giacalone J., Lindgren V., Distèche C., Pagon R. A., Hofker M. H., van Ommen G. J., Pearson P. L. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am J Hum Genet. 1985 Mar;37(2):250–267. [PMC free article] [PubMed] [Google Scholar]
  11. Francke U., Yang-Feng T. L., Brissenden J. E., Ullrich A. Chromosomal mapping of genes involved in growth control. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):855–866. doi: 10.1101/sqb.1986.051.01.099. [DOI] [PubMed] [Google Scholar]
  12. Harper M. E., Saunders G. F. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. doi: 10.1007/BF00327364. [DOI] [PubMed] [Google Scholar]
  13. Huijing F. Phosphorylase kinase deficiency. Biochem Genet. 1970 Feb;4(1):187–194. doi: 10.1007/BF00484029. [DOI] [PubMed] [Google Scholar]
  14. Jackson I. J., LeCras T. D., Docherty A. J. Assignment of the TIMP gene to the murine X-chromosome using an inter-species cross. Nucleic Acids Res. 1987 May 26;15(10):4357–4357. doi: 10.1093/nar/15.10.4357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kilimann M. W., Zander N. F., Kuhn C. C., Crabb J. W., Meyer H. E., Heilmeyer L. M., Jr The alpha and beta subunits of phosphorylase kinase are homologous: cDNA cloning and primary structure of the beta subunit. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9381–9385. doi: 10.1073/pnas.85.24.9381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lebo R. V., Gorin F., Fletterick R. J., Kao F. T., Cheung M. C., Bruce B. D., Kan Y. W. High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome to chromosome 11. Science. 1984 Jul 6;225(4657):57–59. doi: 10.1126/science.6587566. [DOI] [PubMed] [Google Scholar]
  17. Lindgren V., de Martinville B., Horwich A. L., Rosenberg L. E., Francke U. Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus. Science. 1984 Nov 9;226(4675):698–700. doi: 10.1126/science.6494904. [DOI] [PubMed] [Google Scholar]
  18. Lubahn D. B., Joseph D. R., Sullivan P. M., Willard H. F., French F. S., Wilson E. M. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science. 1988 Apr 15;240(4850):327–330. doi: 10.1126/science.3353727. [DOI] [PubMed] [Google Scholar]
  19. Lyon J. B., Jr, Porter J., Robertson M. Phosphorylase b kinase inheritance in mice. Science. 1967 Mar 24;155(3769):1550–1551. doi: 10.1126/science.155.3769.1550. [DOI] [PubMed] [Google Scholar]
  20. Malthus R., Clark D. G., Watts C., Sneyd J. G. Glycogen-storage disease in rats, a genetically determined deficiency of liver phosphorylase kinase. Biochem J. 1980 Apr 15;188(1):99–106. doi: 10.1042/bj1880099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Migeon B. R., Huijing F. Glycogen-storage disease associated with phosphorylase kinase deficiency: evidence for X inactivation. Am J Hum Genet. 1974 May;26(3):360–368. [PMC free article] [PubMed] [Google Scholar]
  22. Mizuta K., Hashimoto E., Tsutou A., Eishi Y., Takemura T., Narisawa K., Yamamura H. A new type of glycogen storage disease caused by deficiency of cardiac phosphorylase kinase. Biochem Biophys Res Commun. 1984 Mar 15;119(2):582–587. doi: 10.1016/s0006-291x(84)80288-0. [DOI] [PubMed] [Google Scholar]
  23. Newgard C. B., Fletterick R. J., Anderson L. A., Lebo R. V. The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14. Am J Hum Genet. 1987 Apr;40(4):351–364. [PMC free article] [PubMed] [Google Scholar]
  24. Newgard C. B., Littman D. R., van Genderen C., Smith M., Fletterick R. J. Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes. J Biol Chem. 1988 Mar 15;263(8):3850–3857. [PubMed] [Google Scholar]
  25. Ryder-Cook A. S., Sicinski P., Thomas K., Davies K. E., Worton R. G., Barnard E. A., Darlison M. G., Barnard P. J. Localization of the mdx mutation within the mouse dystrophin gene. EMBO J. 1988 Oct;7(10):3017–3021. doi: 10.1002/j.1460-2075.1988.tb03165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Scambler P. J., McPherson M. A., Bates G., Bradbury N. A., Dormer R. L., Williamson R. Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis. Hum Genet. 1987 Jul;76(3):278–282. doi: 10.1007/BF00283623. [DOI] [PubMed] [Google Scholar]
  27. Schimke R. N., Zakheim R. M., Corder R. C., Hug G. Glycogen storage disease type IX: benign glycogenosis of liver and hepatic phosphorylase kinase deficiency. J Pediatr. 1973 Dec;83(6):1031–1034. doi: 10.1016/s0022-3476(73)80544-x. [DOI] [PubMed] [Google Scholar]
  28. SenGupta B., Friedberg F., Detera-Wadleigh S. D. Molecular analysis of human and rat calmodulin complementary DNA clones. Evidence for additional active genes in these species. J Biol Chem. 1987 Dec 5;262(34):16663–16670. [PubMed] [Google Scholar]
  29. Servidei S., Metlay L. A., Chodosh J., DiMauro S. Fatal infantile cardiopathy caused by phosphorylase b kinase deficiency. J Pediatr. 1988 Jul;113(1 Pt 1):82–85. doi: 10.1016/s0022-3476(88)80535-3. [DOI] [PubMed] [Google Scholar]
  30. Sprang S. R., Acharya K. R., Goldsmith E. J., Stuart D. I., Varvill K., Fletterick R. J., Madsen N. B., Johnson L. N. Structural changes in glycogen phosphorylase induced by phosphorylation. Nature. 1988 Nov 17;336(6196):215–221. doi: 10.1038/336215a0. [DOI] [PubMed] [Google Scholar]
  31. Spurr N. K., Goodfellow P. N., Docherty A. J. Chromosomal assignment of the gene encoding the human tissue inhibitor of metalloproteinases to Xp11.1-p11.4. Ann Hum Genet. 1987 Jul;51(Pt 3):189–194. doi: 10.1111/j.1469-1809.1987.tb00870.x. [DOI] [PubMed] [Google Scholar]
  32. Varsányi M., Vrbica A., Heilmeyer L. M., Jr X-linked dominant inheritance of partial phosphorylase kinase deficiency in mice. Biochem Genet. 1980 Apr;18(3-4):247–261. doi: 10.1007/BF00484240. [DOI] [PubMed] [Google Scholar]
  33. Yang-Feng T. L., DeGennaro L. J., Francke U. Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8679–8683. doi: 10.1073/pnas.83.22.8679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yang-Feng T. L., Floyd-Smith G., Nemer M., Drouin J., Francke U. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4. Am J Hum Genet. 1985 Nov;37(6):1117–1128. [PMC free article] [PubMed] [Google Scholar]
  35. Yunis J. J., Prakash O. The origin of man: a chromosomal pictorial legacy. Science. 1982 Mar 19;215(4539):1525–1530. doi: 10.1126/science.7063861. [DOI] [PubMed] [Google Scholar]
  36. Zander N. F., Meyer H. E., Hoffmann-Posorske E., Crabb J. W., Heilmeyer L. M., Jr, Kilimann M. W. cDNA cloning and complete primary structure of skeletal muscle phosphorylase kinase (alpha subunit). Proc Natl Acad Sci U S A. 1988 May;85(9):2929–2933. doi: 10.1073/pnas.85.9.2929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. de Martinville B., Kunkel L. M., Bruns G., Morlé F., Koenig M., Mandel J. L., Horwich A., Latt S. A., Gusella J. F., Housman D. Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus. Am J Hum Genet. 1985 Mar;37(2):235–249. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES