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Gene Review

PENK  -  proenkephalin

Homo sapiens

Synonyms: Proenkephalin-A
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Disease relevance of PENK


Psychiatry related information on PENK


High impact information on PENK


Chemical compound and disease context of PENK


Biological context of PENK


Anatomical context of PENK


Associations of PENK with chemical compounds

  • Nerves displaying immunoreactivity (ir) for the proenkephalin (PRO-ENK) derivatives met-enkephalin (ME), leuenkephalin (LE), octapeptide, and heptapeptide (ordered in decreasing frequency) were present in the dorsolateral stroma of human prostate [21].
  • Selective abolition of these patterns with salt, nuclease, or methanol is associated with liberation of immunoprecipitable proenkephalin into the extraction supernatant [1].
  • Since levels of both vasopressin and beta-endorphin were very high, these deficits in proenkephalin B-peptides were selective and do not represent a generalized property of the human pituitary [22].
  • Intrastriatal injection of this compound reduced the striatal PENK expression induced by haloperidol [23].
  • In contrast, a group II mGluR agonist (2R,4R-APDC) administered intrastriatally reduced neither PENK expression nor the above-mentioned parkinsonian-like symptoms [23].

Enzymatic interactions of PENK

  • Finally, furin cleaved proenkephalin to generate peptide B, an unidentified peak between the 18- and 5.3-kDa fragments, and a small amount of the 5.3-kDa fragment [24].

Regulatory relationships of PENK


Other interactions of PENK


Analytical, diagnostic and therapeutic context of PENK

  • Using in situ hybridization histochemistry, we studied the distribution of neurons that express preproopiomelanocortin (pre-POMC), preprodynorphin (pre-PDYN), and preproenkephalin (pre-PENK) gene transcripts within the human hypothalamus and surrounding structures [19].
  • We conclude that endogenous opioids apparently exclusively derived from PRO-ENK may fulfill important comessenger functions in the fine regulation of prostatic stromal tonus and of local vascular perfusion [21].
  • Nuclear proenkephalin, detected by immunofluorescence with a panel of antiproenkephalin monoclonal antibodies, is distributed predominantly in three patterns [1].
  • PENK cDNA was amplified from newt brain in a RACE PCR targeting the 3' end of the newt delta opioid receptor (DOR) [31].
  • Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis [4].


  1. Proenkephalin is a nuclear protein responsive to growth arrest and differentiation signals. Böttger, A., Spruce, B.A. J. Cell Biol. (1995) [Pubmed]
  2. Expression of PC2 and PC1/PC3 in human pheochromocytomas. Konoshita, T., Gasc, J.M., Villard, E., Takeda, R., Seidah, N.G., Corvol, P., Pinet, F. Mol. Cell. Endocrinol. (1994) [Pubmed]
  3. Influence of acute and chronic 1,2,3,4-tetrahydroisoquinoline administration on the expression of proenkephalin mRNA in the rat striatum. Wardas, J., Zapała, M., Lorenc-Koci, E. Polish journal of pharmacology. (2003) [Pubmed]
  4. Stromal mesenchyme cell genes of the human prostate and bladder. Goo, Y.A., Goodlett, D.R., Pascal, L.E., Worthington, K.D., Vessella, R.L., True, L.D., Liu, A.Y. BMC urology [electronic resource]. (2005) [Pubmed]
  5. Identification and characterization of opioid-binding sites present in the Ishikawa human endometrial adenocarcinoma cell line. Hatzoglou, A., Gravanis, A., Margioris, A.N., Zoumakis, E., Castanas, E. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  6. Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study. Alda, M., Turecki, G., Grof, P., Cavazzoni, P., Duffy, A., Grof, E., Ahrens, B., Berghöfer, A., Müller-Oerlinghausen, B., Dvoráková, M., Libigerová, E., Vojtĕchovský, M., Zvolský, P., Joober, R., Nilsson, A., Prochazka, H., Licht, R.W., Rasmussen, N.A., Schou, M., Vestergaard, P., Holzinger, A., Schumann, C., Thau, K., Rouleau, G.A. Am. J. Med. Genet. (2000) [Pubmed]
  7. The proenkephalin gene (PENK) and opioid dependence. Comings, D.E., Blake, H., Dietz, G., Gade-Andavolu, R., Legro, R.S., Saucier, G., Johnson, P., Verde, R., MacMurray, J.P. Neuroreport (1999) [Pubmed]
  8. Opioid peptides in Huntington's disease: alterations in prodynorphin and proenkephalin system. Seizinger, B.R., Liebisch, D.C., Kish, S.J., Arendt, R.M., Hornykiewicz, O., Herz, A. Brain Res. (1986) [Pubmed]
  9. Opioid peptide biosynthesis: enzymatic selectivity and regulatory mechanisms. Costa, E., Mocchetti, I., Supattapone, S., Snyder, S.H. FASEB J. (1987) [Pubmed]
  10. A cross-validation of the Keane and Penk MMPI scales as measures of post-traumatic stress disorder. Watson, C.G., Kucala, T., Manifold, V. Journal of clinical psychology. (1986) [Pubmed]
  11. A cyclic AMP- and phorbol ester-inducible DNA element. Comb, M., Birnberg, N.C., Seasholtz, A., Herbert, E., Goodman, H.M. Nature (1986) [Pubmed]
  12. Polymorphism and absence of Leu-enkephalin sequences in proenkephalin genes in Xenopus laevis. Martens, G.J., Herbert, E. Nature (1984) [Pubmed]
  13. Variations in respiratory distress characterize the acute agonal period during heroin overdose death: relevance to postmortem mRNA studies. Horvath, M.C., Hurd, Y.L., Rajs, J., Keller, E. Brain Res. Bull. (2006) [Pubmed]
  14. Novel interactions between human T-cell leukemia virus type I Tax and activating transcription factor 3 at a cyclic AMP-responsive element. Low, K.G., Chu, H.M., Schwartz, P.M., Daniels, G.M., Melner, M.H., Comb, M.J. Mol. Cell. Biol. (1994) [Pubmed]
  15. Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1. Yin, J., Lee, J.A., Howells, R.D. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  16. Contingency does not contribute to the effects of cocaine self-administration on prodynorphin and proenkephalin gene expression in the rat forebrain. Ziółkowska, B., Stefański, R., Mierzejewski, P., Zapart, G., Kostowski, W., Przewłocki, R. Brain Res. (2006) [Pubmed]
  17. Chromosomal localization of the human proenkephalin and prodynorphin genes. Litt, M., Buroker, N.E., Kondoleon, S., Douglass, J., Liston, D., Sheehy, R., Magenis, R.E. Am. J. Hum. Genet. (1988) [Pubmed]
  18. Primary structure of the human proenkephalin gene. Comb, M., Rosen, H., Seeburg, P., Adelman, J., Herbert, E. DNA (1983) [Pubmed]
  19. Opioid precursor gene expression in the human hypothalamus. Sukhov, R.R., Walker, L.C., Rance, N.E., Price, D.L., Young, W.S. J. Comp. Neurol. (1995) [Pubmed]
  20. Antibodies against the amino-terminal portion of pro-enkephalin inhibit DNA synthesis in human peripheral mononuclear cells. Padrós, M.R., Saravia, F., Vindrola, O. J. Neuroimmunol. (1995) [Pubmed]
  21. Regional distribution of opioidergic nerves in human and canine prostates. Aumüller, G., Jungblut, T., Malek, B., Konrad, S., Weihe, E. Prostate (1989) [Pubmed]
  22. Characterization of proenkephalin B-derived opioid peptides in the human hypothalamo-neurohypophyseal axis. Arendt, R.M., Seizinger, B.R., Pasi, A., Mehraein, P., Herz, A. Brain Res. (1985) [Pubmed]
  23. An influence of ligands of metabotropic glutamate receptor subtypes on parkinsonian-like symptoms and the striatopallidal pathway in rats. Ossowska, K., Konieczny, J., Wardas, J., Pietraszek, M., Kuter, K., Wolfarth, S., Pilc, A. Amino Acids (2007) [Pubmed]
  24. Differential processing of proenkephalin by prohormone convertases 1(3) and 2 and furin. Breslin, M.B., Lindberg, I., Benjannet, S., Mathis, J.P., Lazure, C., Seidah, N.G. J. Biol. Chem. (1993) [Pubmed]
  25. Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression. Chu, H.M., Tan, Y., Kobierski, L.A., Balsam, L.B., Comb, M.J. Mol. Endocrinol. (1994) [Pubmed]
  26. Regulation of proenkephalin synthesis in adrenal medullary chromaffin cells. Wilson, S.P. J. Neurochem. (1991) [Pubmed]
  27. Comparative distribution of three opioid systems in the lower brainstem of the monkey (Macaca fuscata). Ibuki, T., Okamura, H., Miyazaki, M., Yanaihara, N., Zimmerman, E.A., Ibata, Y. J. Comp. Neurol. (1989) [Pubmed]
  28. T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. Kamphuis, S., Kavelaars, A., Brooimans, R., Kuis, W., Zegers, B.J., Heijnen, C.J. J. Neuroimmunol. (1997) [Pubmed]
  29. A common trans-acting factor is involved in transcriptional regulation of neurotransmitter genes by cyclic AMP. Hyman, S.E., Comb, M., Lin, Y.S., Pearlberg, J., Green, M.R., Goodman, H.M. Mol. Cell. Biol. (1988) [Pubmed]
  30. Identification of a novel prohormone sorting signal-binding site on carboxypeptidase E, a regulated secretory pathway-sorting receptor. Zhang, C.F., Snell, C.R., Loh, Y.P. Mol. Endocrinol. (1999) [Pubmed]
  31. Cloning proenkephalin from the brain of a urodele amphibian (Taricha granulosa) using a DOR-specific primer in a 3'RACE reaction. Walthers, E.A., Moore, F.L. Gen. Comp. Endocrinol. (2005) [Pubmed]
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