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Gene Review

Pu  -  Punch

Drosophila melanogaster

Synonyms: CG9441, DGTPCH, Dmel\CG9441, GCH1, GTP cyclohydrolase 1, ...
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Disease relevance of Pu

  • Axon-tracing experiments demonstrated that neurons expressing a given Gr gene project their axons to a spatially restricted domain of the subesophageal ganglion in the fly brain [1].
  • These studies demonstrate that micromolar levels of reduced pterins may have regulatory effects on GTP cyclohydrolase I and that a mouse mutant is available that has low enough activity to be considered as a model for human atypical phenylketonuria [2].
  • The deduced amino acid sequence of Tetrahrymena GTP cyclohydrolase I showed sequence identity with that of Escherichia coli (55%) [3].

High impact information on Pu

  • A Gr receptor is required for response to the sugar trehalose in taste neurons of Drosophila [4].
  • We recently identified from the Drosophila genome database a large family of G protein-coupled receptor genes, the Gr genes, and predicted that they encode taste receptors on the basis of their structure and specificity of expression [4].
  • GTP cyclohydrolase is composed of a highly conserved homodecameric catalytic core and non-conserved N-terminal domains proposed to be regulatory sites [5].
  • Mammalian GTP cyclohydrolase is subject to end-product inhibition via an associated regulatory protein and to positive regulation via phosphorylation, although target residues are unknown [5].
  • The enzyme GTP cyclohydrolase I, which catalyzes the first step in the pteridine biosynthetic pathway, has been purified by at least 4400-fold from Drosophila melanogaster [6].

Biological context of Pu

  • Although enzyme activity cannot be detected prior to larval stages, the locus must also have earlier functions since most homozygous Pu mutants die during embryogenesis [7].
  • Eleven chromosomal deficiencies and several rearrangements in the Pu-tud region of chromosome 2R have been generated and examined cytologically [8].
  • The activity of GTP CH is shown to be closely correlated with the number of Pu+ genes in the genome [9].
  • Defects in the expression of the protein in Punch maternal effect mutants correlate well with the early phenotypes [10].
  • As syncytial blastoderm nuclear divisions proceed, Punch protein levels decrease and disappear by cellularization [10].

Anatomical context of Pu


Associations of Pu with chemical compounds


Other interactions of Pu

  • Late in embryogenesis, a Pu product is necessary for the proper pigmentation of larval cuticle and proper orientation and differentiation of other larval structures, particularly in the head region [7].
  • Individuals heterozygous for the noncomplementing allele, Ddcn7, over the 12-band DDC deficiency, Df (2L)130, die at the end of embryogenesis as unhatched larvae with unpigmented mouth parts [16].
  • At this stage the adult cuticle is unsclerotized and unpigmented and dopa decarboxylase levels, a key enzyme in catecholamine metabolism which provides the crosslinking agents as well as the precursors for melanin, is low [17].
  • Functional interactions between GTP cyclohydrolase I and tyrosine hydroxylase in Drosophila [11].
  • (1973) that zeste is the strucural locus for GTP cyclohydrolase [15].

Analytical, diagnostic and therapeutic context of Pu

  • In order to examine the organization and function of this locus further, we have performed interallelic complementation tests on 25 Punch mutations, monitoring viability and enzyme activity in prepupae and adults [18].


  1. Spatially restricted expression of candidate taste receptors in the Drosophila gustatory system. Dunipace, L., Meister, S., McNealy, C., Amrein, H. Curr. Biol. (2001) [Pubmed]
  2. Effects of sepiapterin and 6-acetyldihydrohomopterin on the guanosine triphosphate cyclohydrolase I of mouse, rat and the fruit-fly Drosophila. Jacobson, K.B., Manos, R.E. Biochem. J. (1989) [Pubmed]
  3. GTP cyclohydrolase I from Tetrahymena pyriformis: cloning of cDNA and expression. Tazawa, M., Ohtsuki, M., Sumi-Ichinose, C., Shiraishi, H., Kuroda, R., Hagino, Y., Nakashima, S., Nozawa, Y., Ichinose, H., Nagatsu, T., Nomura, T. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2000) [Pubmed]
  4. A Gr receptor is required for response to the sugar trehalose in taste neurons of Drosophila. Dahanukar, A., Foster, K., van der Goes van Naters, W.M., Carlson, J.R. Nat. Neurosci. (2001) [Pubmed]
  5. A typical N-terminal Extensions Confer Novel Regulatory Properties on GTP Cyclohydrolase Isoforms in Drosophila melanogaster. Funderburk, C.D., Bowling, K.M., Xu, D., Huang, Z., O'donnell, J.M. J. Biol. Chem. (2006) [Pubmed]
  6. Purification and characterization of GTP cyclohydrolase I from Drosophila melanogaster. Weisberg, E.P., O'Donnell, J.M. J. Biol. Chem. (1986) [Pubmed]
  7. An analysis of the embryonic defects in Punch mutants of Drosophila melanogaster. Reynolds, E.R., O'Donnell, J.M. Dev. Biol. (1987) [Pubmed]
  8. A cytogenetic analysis of the Punch-tudor region of chromosome 2R in Drosophila melanogaster. O'Donnell, J., Boswell, R., Reynolds, T., Mackay, W. Genetics (1989) [Pubmed]
  9. A genetic analysis of the pteridine biosynthetic enzyme, guanosine triphosphate cyclohydrolase, in Drosophila melanogaster. Mackay, W.J., O'Donnell, J.M. Genetics (1983) [Pubmed]
  10. A maternal product of the Punch locus of Drosophila melanogaster is required for precellular blastoderm nuclear divisions. Chen, X., Reynolds, E.R., Ranganayakulu, G., O'Donnell, J.M. J. Cell. Sci. (1994) [Pubmed]
  11. Functional interactions between GTP cyclohydrolase I and tyrosine hydroxylase in Drosophila. Krishnakumar, S., Burton, D., Rasco, J., Chen, X., O'Donnell, J. J. Neurogenet. (2000) [Pubmed]
  12. Maternal and zygotic control of serotonin biosynthesis are both necessary for Drosophila germband extension. Colas, J.F., Launay, J.M., Maroteaux, L. Mech. Dev. (1999) [Pubmed]
  13. Molecular and developmental genetics of the Punch locus, a pterin biosynthesis gene in Drosophila melanogaster. O'Donnell, J.M., McLean, J.R., Reynolds, E.R. Dev. Genet. (1989) [Pubmed]
  14. RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter. Wu, S.M., Kuo, W.C., Hwu, W.L., Hwa, K.Y., Mantovani, R., Lee, Y.M. Mol. Pharmacol. (2004) [Pubmed]
  15. Correlation of guanosine triphosphate cyclohydrolase activity and the synthesis of pterins in Drosophila melanogaster. Fan, C.L., Hall, L.M., Skrinska, A.J., Brown, G.M. Biochem. Genet. (1976) [Pubmed]
  16. The genetics of dopa decarboxylase in Drosophila melanogaster. II. Isolation and characterization of dopa-decarboxylase-deficient mutants and their relationship to the alpha-methyl-dopa-hypersensitive mutants. Wright, T.R., Bewley, G.C., Sherald, A.F. Genetics (1976) [Pubmed]
  17. Temporal and spatial expression of the yellow gene in correlation with cuticle formation and dopa decarboxylase activity in Drosophila development. Walter, M.F., Black, B.C., Afshar, G., Kermabon, A.Y., Wright, T.R., Biessmann, H. Dev. Biol. (1991) [Pubmed]
  18. Tissue-specific and complex complementation patterns in the Punch locus of Drosophila melanogaster. Mackay, W.J., Reynolds, E.R., O'Donnell, J.M. Genetics (1985) [Pubmed]
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