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Gene Review

Proc  -  Proctolin

Drosophila melanogaster

Synonyms: CG7105, Dmel\CG7105, PROC, PROCT, Prct, ...
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Disease relevance of Proct

  • Two genes in Drosophila, rdgA and rdgB, which when defective cause retinal degeneration, were discovered by Hotta and Benzer (Hotta, Y., and S. Benzer. 1970. Proc. Natl, Acad. Sci. U. S, A. 67:1156-1163) [1].

Psychiatry related information on Proct

  • In D. melanogaster, three allelic per mutations have been isolated which affect the periodicity of the circadian oscillators affecting both eclosion and locomotor activity [Konopka, R. & Benzer S. (1971) Proc. Natl. Acad. Sci. USA 68, 2112-2116] [2].
  • Drosophila carrying the X-linked mutation dunce (dnc) showed poor learning in a negative reinforcement olfactory conditioning paradigm (Dudai, Y., Y.-N. Jan, D. Byers, W.G. Quinn, and S. Benzer (1976) Proc. Natl. Acad. Sci. U.S.A. 73: 1684-1688) [3].

High impact information on Proct

  • We show that the Mhc1 mutation is essentially a null allele which results in the dominant-flightless and recessive-lethal phenotypes associated with this mutant (Mogami, K., P. T. O'Donnell, S. I. Bernstein, T. R. F. Wright, C. P. Emerson, Jr. 1986. Proc. Natl. Acad. Sci. USA. 83:1393-1397) [4].
  • In competition-based studies, the CG6986 receptor binds proctolin with high affinity (IC(50) = 4 nM) [5].
  • Proctolin is a bioactive neuropeptide that modulates interneuronal and neuromuscular synaptic transmission in a wide variety of arthropods [5].
  • This is a 16-bp deletion in the 5' region of a desaturase gene (desat2) that was recently suggested to be responsible for the CH polymorphism on the basis of its expression [Dallerac, R., Labeur, C., Jallon, J.-M., Knipple, D. C., Roelofs, W. L. & Wicker-Thomas, C. (2000) Proc. Natl. Acad. Sci. 97, 9449--9454] [6].
  • Waters and colleagues recently suggested [Waters, L. C., Zelhof, A. C., Shaw, B. J. & Ch'ang, L.-Y. (1992) Proc. Natl. Acad. Sci. USA 89, 4855-4859] that an insertion of a long terminal repeat of transposable element 17.6 into the 3' untranslated region of a P450 gene leads to susceptibility to the insecticide DDT in Drosophila melanogaster [7].

Biological context of Proct

  • In addition, low concentration of the specific DPP III inhibitor tynorphin prevented proctolin degradation (IC50 = 0.62 +/- 0.15 micro m) [8].
  • Northern blots showed that the Drosophila proctolin receptor was only weakly expressed in embryos, larvae, pupae, and in the thoraces and abdomina of adult flies, but strongly in the heads of adult animals [9].
  • To account for the transmission of mitochondrial DNA between conspecific species Drosophila pseudoobscura and D. persimilis in sympatry reported by J.R. Powell [Powell, J.R. (1983) Proc. Natl. Acad. Sci. USA 80, 492-495], a simple model of gene flow and selection in infinite populations is analyzed [10].
  • When expressed in mammalian cells, CG6986 confers second messenger activation after proctolin application, with an EC(50) of 0.3 nM [5].
  • The catalytic activity of topoisomerase II is stimulated approximately 2-3-fold following phosphorylation by casein kinase II (Ackerman, P., Glover, C. V. C., and Osheroff, N. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 3164-3168) [11].

Anatomical context of Proct

  • Two proctolin-binding proteins solubilized from 1600 cockroach hindgut membranes were purified 1000-fold using five chromatography steps [12].
  • Finally, anti-(DPP III) immunoreactivity was observed in the central nervous system of D. melanogaster larva, supporting a functional role for DPP III in proctolin degradation [13].
  • In this report, we have disrupted all somatic copies of the Tetrahymena HHP1 gene, which encodes an HP1-like protein, Hhp1p, in macronuclei (H. Huang, E. A. Wiley, R. C. Lending, and C. D. Allis, Proc. Natl. Acad. Sci. USA 95:13624-13629, 1998) [14].
  • We have previously identified an exceptional mRNA that appears to be depleted from early-embryo polysomes [Fruscoloni, P., Al-Atia, G. R., & Jacobs-Lorena, M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3359-3363] [15].
  • The distribution of proctolin suggests roles as a neuromodulator in motoneurons and interneurons, and as a neurohormone that could be released from brain neurosecretory cells with terminations in the ring gland [16].

Associations of Proct with chemical compounds

  • The purified proteins removed the N-terminal dipeptide from the insect myotropic neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) with a Km value of 3.8 +/- 1.1 microM [12].
  • Substance P and proctolin were found in seven and eight out of ten clones, respectively [17].
  • It has been proposed that uric acid is an important scavenger of deleterious oxygen radicals in biological systems [Ames, B. N., Cathcart, R., Schwiers, E. & Hochstein, P. (1981) Proc. Natl. Acad. Sci. USA 78, 6858-6852] [18].
  • This system was chosen because of the previous investigations [Dion, A.S. & Herbst, E.J. (1967) Proc. Natl. Acad. Sci. U.S.A. 58, 2367-2371; Herbst, E.J. & Dion, A.S. (1970) Fed. Proc. Fed. Am. Soc. Exp. Biol. 29, 1563-1567] relating putrescine and spermidine to growth and development of Drosophila [19].
  • The neurons express several synaptic cotransmitters, including glutamate, proctolin, and octopamine, and are specialized by their synaptic morphology, neurotransmitters, and connectivity [20].

Regulatory relationships of Proct

  • These results constitute the first characterization of an evolutionarily conserved insect DPP III that is expressed as a cytosolic and a membrane peptidase involved in proctolin degradation [8].

Analytical, diagnostic and therapeutic context of Proct


  1. Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process. Harris, W.A., Stark, W.S. J. Gen. Physiol. (1977) [Pubmed]
  2. Circadian rhythm mutations in Drosophila melanogaster affect short-term fluctuations in the male's courtship song. Kyriacou, C.P., Hall, J.C. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  3. Cyclic adenosine 3':5'-monophosphate phosphodiesterase and its role in learning in Drosophila. Shotwell, S.L. J. Neurosci. (1983) [Pubmed]
  4. Molecular and ultrastructural defects in a Drosophila myosin heavy chain mutant: differential effects on muscle function produced by similar thick filament abnormalities. O'Donnell, P.T., Bernstein, S.I. J. Cell Biol. (1988) [Pubmed]
  5. Identification and characterization of a G protein-coupled receptor for the neuropeptide proctolin in Drosophilamelanogaster. Johnson, E.C., Garczynski, S.F., Park, D., Crim, J.W., Nassel, D.R., Taghert, P.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. The nucleotide changes governing cuticular hydrocarbon variation and their evolution in Drosophila melanogaster. Takahashi, A., Tsaur, S.C., Coyne, J.A., Wu, C.I. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. Noninvolvement of the long terminal repeat of transposable element 17.6 in insecticide resistance in Drosophila. Delpuech, J.M., Aquadro, C.F., Roush, R.T. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  8. Characterization of a functionally expressed dipeptidyl aminopeptidase III from Drosophila melanogaster. Mazzocco, C., Fukasawa, K.M., Auguste, P., Puiroux, J. Eur. J. Biochem. (2003) [Pubmed]
  9. Molecular identification of the first insect proctolin receptor. Egerod, K., Reynisson, E., Hauser, F., Williamson, M., Cazzamali, G., Grimmelikhuijzen, C.J. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  10. Mitochondrial gene flow. Takahata, N., Slatkin, M. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  11. Effect of casein kinase II-mediated phosphorylation on the catalytic cycle of topoisomerase II. Regulation of enzyme activity by enhancement of ATP hydrolysis. Corbett, A.H., DeVore, R.F., Osheroff, N. J. Biol. Chem. (1992) [Pubmed]
  12. Purification, partial sequencing and characterization of an insect membrane dipeptidyl aminopeptidase that degrades the insect neuropeptide proctolin. Mazzocco, C., Fukasawa, K.M., Raymond, A.A., Puiroux, J. Eur. J. Biochem. (2001) [Pubmed]
  13. Identification and characterization of two dipeptidyl-peptidase III isoforms in Drosophila melanogaster. Mazzocco, C., Gillibert-Duplantier, J., Neaud, V., Fukasawa, K.M., Claverol, S., Bonneu, M., Puiroux, J. FEBS J. (2006) [Pubmed]
  14. A nonessential HP1-like protein affects starvation-induced assembly of condensed chromatin and gene expression in macronuclei of Tetrahymena thermophila. Huang, H., Smothers, J.F., Wiley, E.A., Allis, C.D. Mol. Cell. Biol. (1999) [Pubmed]
  15. Translational regulation of mRNAs for ribosomal proteins during early Drosophila development. Al-Atia, G.R., Fruscoloni, P., Jacobs-Lorena, M. Biochemistry (1985) [Pubmed]
  16. Identification of a proctolin preprohormone gene (Proct) of Drosophila melanogaster: expression and predicted prohormone processing. Taylor, C.A., Winther, A.M., Siviter, R.J., Shirras, A.D., Isaac, R.E., Nässel, D.R. J. Neurobiol. (2004) [Pubmed]
  17. Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system, II: Neuropeptides and amino acids. Ui-Tei, K., Sakuma, M., Watanabe, Y., Miyake, T., Miyata, Y. Neurosci. Lett. (1995) [Pubmed]
  18. Urate-null rosy mutants of Drosophila melanogaster are hypersensitive to oxygen stress. Hilliker, A.J., Duyf, B., Evans, D., Phillips, J.P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  19. The effect of polyamines on the synthesis of ribonucleic acid by Drosophila melanogaster larvae. Byus, C.V., Herbst, E.J. Biochem. J. (1976) [Pubmed]
  20. Cellular mechanisms governing synaptic development in Drosophila melanogaster. Keshishian, H., Chiba, A., Chang, T.N., Halfon, M.S., Harkins, E.W., Jarecki, J., Wang, L., Anderson, M., Cash, S., Halpern, M.E. J. Neurobiol. (1993) [Pubmed]
  21. Identification of the neuropeptide transmitter proctolin in Drosophila larvae: characterization of muscle fiber-specific neuromuscular endings. Anderson, M.S., Halpern, M.E., Keshishian, H. J. Neurosci. (1988) [Pubmed]
  22. Multiple kinesin-like transcripts in Xenopus oocytes. Vernos, I., Heasman, J., Wylie, C. Dev. Biol. (1993) [Pubmed]
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