Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of a series of Ah receptor (AhR) deletion mutants in an in vitro translation system has been previously used to map several functional domains of the murine AhR (Dolwick et al. (1993) Proc. Natl. Acad. Sci. USA 90, 8566-8570). In this report, quantitative immunoprecipitation of 90-kDa heat shock protein (hsp90) from reticulocyte lysate allowed us to measure the level of the AhR and AhR deletion mutants complexed with hsp90. After translation of a series of deletion mutants it was determined that there are two distinct domains important in forming a stable AhR/hsp90 complex, corresponding to amino acid sequences 1-166 and 289-347 of the AhR. Neither ARNT, nor Per were able to stably interact with hsp90. Thus, the AhR appears to be a unique member of the PAS domain family of proteins that binds a known ligand and stably interacts with hsp90.
Biochem Mol Biol Int 1996 Jun
PMID:Mapping the 90 kDa heat shock protein binding region of the Ah receptor. 882 11

A 44-year-old women was treated for hyperparathyroidism resulting from parathyroid hyperplasia. Several months later, following a flu-like episode, she developed fever, confusion, abdominal pain, and diffuse petechiae, with severe thrombocytopenia and hemolytic anemia. She died on the 11th day of hospitalization. At autopsy she had multiple endocrine neoplasia type I, with two islet cell tumors, adrenal adenoma, pituitary adenoma, and bronchial carcinoid with liver metastasis. Florid visceral microthrombi involved arterioles and capillaries of the heart, including the conduction system. Brain, kidney, pancreas, adrenal, and portal areas of the liver were also heavily involved, but thrombi were rare in the liver sinusoids and the lungs. PAS-positive subendothelial deposits were demonstrated. In spite of the disseminated malignancy, the morphologic and laboratory findings were inconsistent with disseminated intravascular coagulation (DIC), and supported the clinical diagnosis of TTP. To the best of our knowledge this is the first report association of TTP with MEN and raises the question of a genetic linkage and/or hormonal interaction.
Hematopathol Mol Hematol 1996
PMID:Fatal thrombotic thrombocytopenic purpura (TTP) presenting concurrently with metastatic multiple endocrine neoplasia (MEN) type I. 887 34

The major protein in occytes of the barnacle Balanus amphitrite has been identified as vitellin (Vt) and its biochemical properties partially characterized. SDS-PAGE of protein extracts from different developmental stages of occytes and embryos of B. amphitrite revealed that a 170 kDa polypeptide was abundantly present in fully matured oocytes. Its amount increased with occyte maturation and decreased with embryonic development after fertilization. Antiserum, prepared against 170 kDa polypeptide, was found to recognize only 170 kDa among proteins in ovary extract (OE) by immunoblot analysis. Immunohistochemical study indicated localization of 170 kDa polypeptide in yolk granules of oocytes, oviducts and embryos. Combination of native electrophoresis with agarose gel and SDS-PAGE displayed that the main protein in OE was lipophilic, contained 85 kDa polypeptide in addition of 170 kDa, and was positive in PAS reaction. The main peak eluted from OE contained 170 kDa and 85 kDa polypeptides, and corresponded to 200 kDa when filtrated through superose 6 gel. Conclusively, vitellin of B. amphitrite is a lipophilic glycoprotein consisting of two subunits, a heavy chain with 170 kDa and a light chain with 85 kDa. Two other barnacles, Megabalanus rosa and Tetraclita squamosa japonica, also contained proteins similar to B. amphitrite Vt.
Comp Biochem Physiol B Biochem Mol Biol 1996 Sep
PMID:Identification and partial characterization of vitellin from the barnacle Balanus amphitrite. 889 36

From a cDNA library of mouse skeletal muscle, we have isolated mouse Sim1 (mSim1) cDNA encoding a polypeptide of 765 amino acids with striking amino acid identify in basic helix-loop-helix (89% identify) and PAS (89 % identify) domains to previously identified mSim2, although the carboxy-terminal third of the molecule did not show any similarity to mSim2 or Drosophila Sim (dSim). Yeast two-hybrid analysis and coimmunoprecipitation experiments demonstrated that both of the mSim gene products interacted with Arnt even more efficiently than AhR, a natural partner of Arnt, suggesting a functional cooperativity with Arnt. In sharp contrast with dSim having transcriptional-enhancing activity in the carboxy-terminal region, the two mSims possessed a repressive activity toward Arnt in the heterodimer complex. This is the first example of bHLH-PAS proteins with transrepressor activity, although some genetic data suggest that dSim plays a repressive role in gene expression (Z. Chang, D. Price, S. Bockheim, M. J. Boedigheimer, R. Smith, and A. Laughon, Dev. Biol. 160:315-322, 1993; D. M. Mellerick and M. Nirenberg, Dev. Biol. 171:306-316, 1995). Whole-mount in situ hybridization showed restricted and characteristic expression patterns of the two mSim mRNAs in various tissues and organs during embryogenesis, such as those for the somite, the nephrogenic cord, and the mesencephalon (for mSim1) and those for the diencephalon, branchial arches, and limbs (for mSim2). From sequence similarity and chromosomal localization, it is concluded that mSim2 is an ortholog of hSim2, which is proposed to be a candidate gene responsible for Down's syndrome. The sites of mSim2 expression showed an overlap with the affected regions of the syndrome, further strengthening involvement of mSim2 in Down's syndrome.
Mol Cell Biol 1996 Oct
PMID:Two new members of the murine Sim gene family are transcriptional repressors and show different expression patterns during mouse embryogenesis. 892 54

The period (per) locus has received much attention in molecular evolution studies because it is one of the best studied "behavioral genes" and because it offers insight into the evolution of repetitive sequences. We studied most of the coding region of per in Drosophila willistoni and confirmed previously observed patterns of conservation and divergence among distantly related species. Five regions are so highly diverged that they cannot be aligned, whereas a region encompassing the PAS domain is very conserved. Structural and nucleotide polymorphism patterns in the willistoni group are not the same as those observed in previously studied species. We sequenced the region homologous to the highly polymorphic threonine-glycine repeat of D. melanogaster in multiple strains of D. willistoni, as well as in other members of willistoni group, and found an unusual amount of conservation in this region. However, the next nonconserved region downstream in the sequence is quite variable and polymorphic for the number of repeated glycines. The glycine codon usage is significantly different in this glycine repeat as compared to other parts of the gene. We were able to plot the directionality of change in the glycine repeat region onto a phylogeny and find that the addition of glycines is the general trend with the diversification of the willistoni group.
Mol Biol Evol 1997 Jul
PMID:Interspecific and intraspecific comparisons of the period locus in the Drosophila willistoni sibling species. 921 47

The Drosophila single-minded (Dsim) gene encodes a master regulatory protein involved in cell fate determination during midline development. This protein is a member of a rapidly expanding family of gene products possessing basic helix-loop-helix (bHLH) and hydrophobic PAS (designated a conserved region among PER, ARNT [aryl hydrocarbon receptor nuclear translocator] and SIM) protein association domains. Members of this family function as central transcriptional regulators in cellular differentiation and in the response to environmental stimuli such as xenobiotics and hypoxia. We have previously identified a murine member of this family, called mSim-2, showing sequence homology to the bHLH and PAS domains of Dsim. Immunoprecipitation experiments with recombinant proteins indicate that mSIM-2 associates with the arnt gene product. In the present work, by using fine-structure mapping we found that the HLH and PAS motifs of both proteins are required for optimal association. Forced expression of GAL4/mSIM-2 fusion constructs in mammalian cells demonstrated the presence of two separable repression domains within the carboxy terminus of mSIM-2. We found that mSIM-2 is capable of repressing ARNT-mediated transcriptional activation in a mammalian two-hybrid system. This effect (i) is dependent on the ability of mSIM-2 and ARNT to heterodimerize, (ii) is dependent on the presence of the mSIM-2 carboxy-terminal repression domain, and (iii) is not specific to the ARNT activation domain. These results suggest that mSIM-2 repression activity can dominantly override the activation potential of adjacent transcription factors. We also demonstrated that mSIM-2 can functionally interfere with hypoxia-inducible factor 1alpha (HIF-1alpha)/ARNT transcription complexes, providing a second mechanism by which mSIM-2 may inhibit transcription.
Mol Cell Biol 1997 Sep
PMID:The murine Sim-2 gene product inhibits transcription by active repression and functional interference. 927 72

Azotobacter vinelandii NIFL is a nitrogen fixation-specific regulatory flavoprotein that modulates the activity of the transcriptional activator NIFA in response to oxygen and fixed nitrogen in vivo. NIFL is also responsive to ADP in vitro. Limited proteolysis of NIFL indicates that it comprises a relatively stable N-terminal domain and a C-terminal domain that is protected from trypsin digestion in the presence of adenosine nucleotides. ATP protects the protein from cleavage in the vicinity of potential nucleotide-binding sites in the C-terminus, whereas ADP protects the entire C-terminal domain. NIFL has an apparent Kd of 130 microM for ATP and 16 microM for ADP. The purified N-terminal domain has an identical UV/visible absorption spectrum to the wild-type protein and is reduced by sodium dithionite, demonstrating that it is a flavin-binding domain. The isolated N-terminal domain does not inhibit NIFA activity. A subdomain fragment containing 160 residues of the C-terminal region, including the nucleotide-binding sites, is also not competent to inhibit NIFA. Removal of the first 146 residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in a large family of sensory proteins from eubacteria, archea and eukarya eliminates the redox response. However, this truncated protein remains competent to inhibit NIFA activity in response to ADP in vitro and to the level of fixed nitrogen in vivo. The redox and nitrogen-sensing functions of A. vinelandii NIFL are therefore separable and are discrete functions of the protein.
Mol Microbiol 1998 Apr
PMID:The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains. 959 6

The genes coding for white collar-1 and white collar-2 (wc-1 and wc-2) have been isolated previously, and their products characterized as Zn-finger transcription factors involved in the control of blue light-induced genes. Here, we show that the PAS dimerization domains present in both proteins enable the WC-1 and WC-2 proteins to dimerize in vitro. Homodimers and heterodimers are formed between the white collar (WC) proteins. A computer analysis of WC-1 reveals a second domain, called LOV, also identified in NPH1, a putative blue light photoreceptor in plants and conserved in redox-sensitive proteins and in the phytochromes. The WC-1 LOV domain does not dimerize with canonical PAS domains, but it is able to self-dimerize. The isolation of three blind wc-1 strains, each with a single amino acid substitution only in the LOV domain, reveals that this region is essential for blue light responses in Neurospora. The demonstration that the WC-1 proteins in these LOV mutants are still able to self-dimerize suggests that this domain plays an additional role, essential in blue light signal transduction.
Mol Microbiol 1998 Aug
PMID:Roles in dimerization and blue light photoresponse of the PAS and LOV domains of Neurospora crassa white collar proteins. 972 12

Two cysteine proteinase inhibitors, designated Tromsin I and II, were purified from the skin of Atlantic salmon, using three steps of chromatography, including affinity, anion exchange and gelfiltration. The two cysteine proteinase inhibitors were both of the high molecular weight type, with apparent MW 49 and 76 kDa. The isoelectric points (pI) of Tromsin I and II were estimated to be 4.5 and 5.2, respectively. The inhibitors were both stained by the PAS reaction for carbohydrates, and showed a remarkable heat stability. Western blotting revealed that the inhibitors also could be found in significant amounts in serum. Tromsin I and II share many common features with members of the family 3 cystatins, i.e. mammalian kininogen, such as molecular weight, papain inhibition and tissue distribution. Based on N-terminal sequence from Tromsin II however, no homology with known cysteine proteinase inhibitors can be found. This does not exclude that the inhibitors belong to the family 3 cystatins, because the N-terminal amino acid sequences of known cysteine proteinase inhibitors show very low homology.
Comp Biochem Physiol B Biochem Mol Biol 1998 Nov
PMID:Purification and characterization of two cysteine proteinase inhibitors from the skin of Atlantic salmon (Salmo salar L.). 997 99

PAS domains are newly recognized signaling domains that are widely distributed in proteins from members of the Archaea and Bacteria and from fungi, plants, insects, and vertebrates. They function as input modules in proteins that sense oxygen, redox potential, light, and some other stimuli. Specificity in sensing arises, in part, from different cofactors that may be associated with the PAS fold. Transduction of redox signals may be a common mechanistic theme in many different PAS domains. PAS proteins are always located intracellularly but may monitor the external as well as the internal environment. One way in which prokaryotic PAS proteins sense the environment is by detecting changes in the electron transport system. This serves as an early warning system for any reduction in cellular energy levels. Human PAS proteins include hypoxia-inducible factors and voltage-sensitive ion channels; other PAS proteins are integral components of circadian clocks. Although PAS domains were only recently identified, the signaling functions with which they are associated have long been recognized as fundamental properties of living cells.
Microbiol Mol Biol Rev 1999 Jun
PMID:PAS domains: internal sensors of oxygen, redox potential, and light. 1035 59


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