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

• 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 [13].
• Fix L, which contains a haemoglobin domain homologous to the PAS family and a histidine kinase domain, forms, with Fix J, a two-component signalling complex that regulates expression of nitrogenase genes in Rhizobium [14].
• Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependent fashion; 50 mg.kg(-1).d(-1) decreased the AB/PAS area to 22.7% +/- 2.7% (P <.05 compared with OVA sensitization alone) [15].
• Protamine sulfate administration resulted in hypotension (delta BP -64 mm Hg), pulmonary hypertension (delta PAS + 13 mm Hg, delta PAD + 11 mm Hg), and bradycardia (delta HR -30) [16].
• Oestradiol-17 beta treatment caused PAS-positive cells in the proximal pars distalis, presumably a mixture of gonadotrops and thyrotrops, to undergo hypertrophy, vacuolation and degranulation of cytoplasmic glycoprotein granules [17].

Biological context of PAS

• PAS genes are required for peroxisome biogenesis in the yeast S. cerevisiae [18].
• PAS is a dimerization domain common to Drosophila period and several transcription factors [19].
• Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression [20].
• These results suggest a model for phototransduction, with implications for bacteriorhodopsin, photoactive proteins, PAS domains, and signalling proteins [21].
• In this review, we summarize this rapidly expanding research area by providing a detailed description of three signal transduction pathways that utilize PAS protein heterodimers to drive their transcriptional output [22].

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

• A recently characterized enzyme, PAS kinase, may be a new member of this group of nutritional transducers [37].
• After infusion of vasoactive intestinal polypeptide the secretory cells, which in the control group were rich in PAS-positive mucin, became almost completely PAS-negative [38].
• The techniques evaluated were direct and indirect fluorescent antibody technique, and four conventional stains: PAS, H & E, Trichrome, and PTAH) [39].
• This molecular genetic dissection of the second of two components of this light signal transduction system has enabled us to devise a model whereby WC1 and WC2 are proposed to interact via homologous PAS domains, bind to promoters of light-regulated genes and activate transcription [40].
• The very early evolutionary development and diverse functions of PAS domains have made sequence analysis and modeling of this protein superfamily challenging [41].

References