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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

AG-J-49390     ethyl 1-(3H-benzoimidazol-5...

Synonyms: CTK6F6830, DNC000626, AC1LA3ZP
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Disease relevance of PAS

  • This protein shares 48% sequence identity with hypoxia inducible factor (HIF-1alpha) and lesser similarity with other members of the basic helix-loop-helix/PAS domain family of transcription factors [1].
  • The Ah receptor (AhR), a bHLH/PAS transcription factor, mediates dioxin toxicity in the immune system, skin, testis and liver [2].
  • These findings indicate a role for the PAS in heart and brain invasion by relapsing fever Borrelia, resulting in organ injury [3].
  • Subcutaneous inoculation of 10(4) spirochetes resulted in a peak spirochetemia five days after infection with 20-23 x 10(6) organisms per milliliter of whole blood in all mice, indicating that the PAS had no effect on the development of this phase of the infection [3].
  • The gene cyaB1 from the cyanobacterium Anabaena sp. PCC 7120 codes for a protein consisting of two N-terminal GAF domains (GAF-A and GAF-B), a PAS domain and a class III adenylyl cyclase catalytic domain [4].

Psychiatry related information on PAS

  • Application of the PAS protocols after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting [5].
  • Thirty-nine female out-patients with bulimia nervosa were assessed for personality disorders using the PAS [6].
  • The instillation of LPS increased AB/PAS and MUC5AC staining in time- and dose-dependent manners, and treatment with MMPI significantly prevented GC metaplasia [7].
  • CONCLUSION: The community pharmacy-based PAS smoking cessation service can be an effective method of helping people stop smoking when delivered by pharmacists willing to adopt this approach [8].
  • The PAS system, subscribed to by many hospitals, is readily adaptable to drug usage review [9].

High impact information on PAS

  • Genetic, biochemical, and physiological data provide evidence that both of these enzymes are inhibited by PAS kinase-dependent phosphorylation, thereby downregulating carbohydrate storage [10].
  • PAS kinase was also found to phosphorylate UDP-glucose pyrophosphorylase and glycogen synthase, the enzymes catalyzing the two final steps in the glycogen biosynthetic pathway [10].
  • Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness [11].
  • ZEITLUPE encodes a novel clock-associated PAS protein from Arabidopsis [12].
  • The PAS region is highly similar to the PAS domain of the Arabidopsis blue-light receptor NPH1, and the Neurospora circadian-associated protein WHITE COLLAR-1 (WC-1) [12].

Chemical compound and disease context of PAS


Biological context of PAS


Anatomical context of PAS

  • In addition, similarities between the PAS-domain regions of molecules involved in light perception and circadian rhythmicity in several organisms suggest an evolutionary link between ancient photoreceptor proteins and more modern proteins required for circadian oscillation [23].
  • Patients whose cells reacted with LS antiserum often had bad prognostic features: mediastinal or abdominal mass, expression of T-cell markers, and PAS negativity [24].
  • Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content [25].
  • Histochemical studies showed (a) 90% of the epithelial cells contained PAS positive granules, (b) 5% of the cells gave a strong reaction for succinic dehydrogenase activity (presumably parietal cells), and (c) immunohistochemical localization of pepsinogen was negative [26].
  • Aer is homologous to E. coli chemoreceptors but unique in having a PAS domain and a flavin-adenine dinucleotide cofactor that is postulated to interact with a component of the electron transport system [27].

Associations of PAS with other chemical compounds

  • Two basic helix-loop-helix (bHLH) PAS (PER-ARNT-SIM) transcription factors, CLOCK and BMAL1, form the positive elements of the system and drive transcription of three Period and two Cryptochrome genes [28].
  • Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex [29].
  • The heme cofactor in its PAS domain can act as a sensor of the cellular redox state that regulates the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase activity [30].
  • The amino acid sequence of PASK specifies two PAS domains followed by a canonical serine/threonine kinase domain, indicating that it might represent the first mammalian PAS-regulated protein kinase [31].
  • The Mak1p histidine kinase, which also contains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially required for Pap1p- and Prr1p-dependent transcription [32].

Gene context of PAS

  • Using a yeast two-hybrid screen, we have identified a phytochrome-interacting factor, PIF3, a basic helix-loop-helix protein containing a PAS domain [33].
  • A heterodimer of the dioxin receptor (AhR) and Arnt, which are basic helix-loop-helix/PAS-family transcription factors, mediates most of the toxic effects of dioxins [34].
  • Clock, a mammalian clock gene encoding a PAS-containing polypeptide, has now been cloned: it is likely that the Per homologues dimerize with other molecule(s) such as Clock through PAS-PAS interaction in the circadian clock system [35].
  • We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS domain of the Per2 protein, show alterations in the glutamatergic system [36].
  • Here we describe the cloning and characterization of a PAS domain transcription factor termed endothelial PAS-1 (EPAS1) [1].

Analytical, diagnostic and therapeutic context of PAS


  1. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Tian, H., McKnight, S.L., Russell, D.W. Genes Dev. (1997) [Pubmed]
  2. p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Kolluri, S.K., Weiss, C., Koff, A., Göttlicher, M. Genes Dev. (1999) [Pubmed]
  3. The plasminogen activation system enhances brain and heart invasion in murine relapsing fever borreliosis. Gebbia, J.A., Monco, J.C., Degen, J.L., Bugge, T.H., Benach, J.L. J. Clin. Invest. (1999) [Pubmed]
  4. A GAF-domain-regulated adenylyl cyclase from Anabaena is a self-activating cAMP switch. Kanacher, T., Schultz, A., Linder, J.U., Schultz, J.E. EMBO J. (2002) [Pubmed]
  5. Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training. Stefan, K., Wycislo, M., Gentner, R., Schramm, A., Naumann, M., Reiners, K., Classen, J. Cereb. Cortex (2006) [Pubmed]
  6. Personality disorder and treatment response in bulimia nervosa. Fahy, T.A., Eisler, I., Russell, G.F. The British journal of psychiatry : the journal of mental science. (1993) [Pubmed]
  7. Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia. Kim, J.H., Lee, S.Y., Bak, S.M., Suh, I.B., Lee, S.Y., Shin, C., Shim, J.J., In, K.H., Kang, K.H., Yoo, S.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  8. A randomized controlled trial of a smoking cessation intervention based in community pharmacies. Maguire, T.A., McElnay, J.C., Drummond, A. Addiction (2001) [Pubmed]
  9. Using the PAS system for hospital drug utilization review. Hoffmann, R.P. Hospital progress. (1979) [Pubmed]
  10. Coordinate regulation of sugar flux and translation by PAS kinase. Rutter, J., Probst, B.L., McKnight, S.L. Cell (2002) [Pubmed]
  11. Mop3 is an essential component of the master circadian pacemaker in mammals. Bunger, M.K., Wilsbacher, L.D., Moran, S.M., Clendenin, C., Radcliffe, L.A., Hogenesch, J.B., Simon, M.C., Takahashi, J.S., Bradfield, C.A. Cell (2000) [Pubmed]
  12. ZEITLUPE encodes a novel clock-associated PAS protein from Arabidopsis. Somers, D.E., Schultz, T.F., Milnamow, M., Kay, S.A. Cell (2000) [Pubmed]
  13. Binding of oxygen and carbon monoxide to a heme-regulated phosphodiesterase from Escherichia coli. Kinetics and infrared spectra of the full-length wild-type enzyme, isolated PAS domain, and Met-95 mutants. Taguchi, S., Matsui, T., Igarashi, J., Sasakura, Y., Araki, Y., Ito, O., Sugiyama, S., Sagami, I., Shimizu, T. J. Biol. Chem. (2004) [Pubmed]
  14. Fix L, a haemoglobin that acts as an oxygen sensor: signalling mechanism and structural basis of its homology with PAS domains. Perutz, M.F., Paoli, M., Lesk, A.M. Chem. Biol. (1999) [Pubmed]
  15. Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice. Shim, J.J., Dabbagh, K., Takeyama, K., Burgel, P.R., Dao-Pick, T.P., Ueki, I.F., Nadel, J.A. J. Allergy Clin. Immunol. (2000) [Pubmed]
  16. Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation. Wakefield, T.W., Ucros, I., Kresowik, T.F., Hinshaw, D.B., Stanley, J.C. J. Vasc. Surg. (1989) [Pubmed]
  17. Effects of oestradiol-17 beta and testosterone on the histology of pituitary, liver, ovary and skin of previtellogenic Epinephelus akaara (Teleostei, Serranidae). Tam, P.P., Ng, T.B., Woo, N.Y. Cell Tissue Res. (1983) [Pubmed]
  18. PAS1, a yeast gene required for peroxisome biogenesis, encodes a member of a novel family of putative ATPases. Erdmann, R., Wiebel, F.F., Flessau, A., Rytka, J., Beyer, A., Fröhlich, K.U., Kunau, W.H. Cell (1991) [Pubmed]
  19. PAS is a dimerization domain common to Drosophila period and several transcription factors. Huang, Z.J., Edery, I., Rosbash, M. Nature (1993) [Pubmed]
  20. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Makino, Y., Cao, R., Svensson, K., Bertilsson, G., Asman, M., Tanaka, H., Cao, Y., Berkenstam, A., Poellinger, L. Nature (2001) [Pubmed]
  21. Structure at 0.85 A resolution of an early protein photocycle intermediate. Genick, U.K., Soltis, S.M., Kuhn, P., Canestrelli, I.L., Getzoff, E.D. Nature (1998) [Pubmed]
  22. The PAS superfamily: sensors of environmental and developmental signals. Gu, Y.Z., Hogenesch, J.B., Bradfield, C.A. Annu. Rev. Pharmacol. Toxicol. (2000) [Pubmed]
  23. Neurospora wc-1 and wc-2: transcription, photoresponses, and the origins of circadian rhythmicity. Crosthwaite, S.K., Dunlap, J.C., Loros, J.J. Science (1997) [Pubmed]
  24. Childhood lymphoblastic cancer: subgroups defined by nonhuman primate antisera to human lymphatic leukemia cell antigens. Raney, R.B., Mohanakumar, T., Metzgar, R.S., Hann, H.W., Donaldson, M.H. J. Natl. Cancer Inst. (1977) [Pubmed]
  25. Macrophagic myofasciitis: an emerging entity. Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l'Association Française contre les Myopathies (AFM). Gherardi, R.K., Coquet, M., Chérin, P., Authier, F.J., Laforêt, P., Bélec, L., Figarella-Branger, D., Mussini, J.M., Pellissier, J.F., Fardeau, M. Lancet (1998) [Pubmed]
  26. Cell culture of rat gastric fundic mucosa. Terano, A., Ivey, K.J., Stachura, J., Sekhon, S., Hosojima, H., McKenzie, W.N., Krause, W.J., Wyche, J.H. Gastroenterology (1982) [Pubmed]
  27. Aerotaxis and other energy-sensing behavior in bacteria. Taylor, B.L., Zhulin, I.B., Johnson, M.S. Annu. Rev. Microbiol. (1999) [Pubmed]
  28. Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation. Lowrey, P.L., Takahashi, J.S. Annu. Rev. Genet. (2000) [Pubmed]
  29. Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex. Lindebro, M.C., Poellinger, L., Whitelaw, M.L. EMBO J. (1995) [Pubmed]
  30. Structure-function relationships of EcDOS, a heme-regulated phosphodiesterase from Escherichia coli. Sasakura, Y., Yoshimura-Suzuki, T., Kurokawa, H., Shimizu, T. Acc. Chem. Res. (2006) [Pubmed]
  31. PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase. Rutter, J., Michnoff, C.H., Harper, S.M., Gardner, K.H., McKnight, S.L. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  32. Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway. Buck, V., Quinn, J., Soto Pino, T., Martin, H., Saldanha, J., Makino, K., Morgan, B.A., Millar, J.B. Mol. Biol. Cell (2001) [Pubmed]
  33. PIF3, a phytochrome-interacting factor necessary for normal photoinduced signal transduction, is a novel basic helix-loop-helix protein. Ni, M., Tepperman, J.M., Quail, P.H. Cell (1998) [Pubmed]
  34. Modulation of oestrogen receptor signalling by association with the activated dioxin receptor. Ohtake, F., Takeyama, K., Matsumoto, T., Kitagawa, H., Yamamoto, Y., Nohara, K., Tohyama, C., Krust, A., Mimura, J., Chambon, P., Yanagisawa, J., Fujii-Kuriyama, Y., Kato, S. Nature (2003) [Pubmed]
  35. Circadian oscillation of a mammalian homologue of the Drosophila period gene. Tei, H., Okamura, H., Shigeyoshi, Y., Fukuhara, C., Ozawa, R., Hirose, M., Sakaki, Y. Nature (1997) [Pubmed]
  36. The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Spanagel, R., Pendyala, G., Abarca, C., Zghoul, T., Sanchis-Segura, C., Magnone, M.C., Lascorz, J., Depner, M., Holzberg, D., Soyka, M., Schreiber, S., Matsuda, F., Lathrop, M., Schumann, G., Albrecht, U. Nat. Med. (2005) [Pubmed]
  37. Nutrient-regulated protein kinases in budding yeast. Wilson, W.A., Roach, P.J. Cell (2002) [Pubmed]
  38. Vasoactive intestinal polypeptidergic nerves and Brunner's gland secretion in the rat. Kirkegaard, P., Lundberg, J.M., Poulsen, S.S., Olsen, P.S., Fahrenkrug, J., Hökfelt, T., Christiansen, J. Gastroenterology (1981) [Pubmed]
  39. Comparison of conventional and immunofluorescent techniques for the detection of Entamoeba histolytica in rectal biopsies. Gilman, R., Islam, M., Paschi, S., Goleburn, J., Ahmad, F. Gastroenterology (1980) [Pubmed]
  40. White collar 2, a partner in blue-light signal transduction, controlling expression of light-regulated genes in Neurospora crassa. Linden, H., Macino, G. EMBO J. (1997) [Pubmed]
  41. Photoactive yellow protein: a structural prototype for the three-dimensional fold of the PAS domain superfamily. Pellequer, J.L., Wager-Smith, K.A., Kay, S.A., Getzoff, E.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
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