Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Yeast endosomes, like those in animal cells, invaginate their membranes to form internal vesicles. The resulting multivesicular bodies fuse with the vacuole, the lysosome equivalent, delivering the internal vesicles for degradation. We have partially purified internal vesicles and analysed their content. Besides the known component carboxypeptidase S (Cps1p), we identified a polyphosphatase (Phm5p), a presumptive haem oxygenase (Ylr205p/Hmx1p) and a protein of unknown function (Yjl151p/Sna3p). All are membrane proteins, and appear to be cargo molecules rather than part of the vesicle-forming machinery. We show that both Phm5p and Cps1p are ubiquitylated, and that in a doa4 mutant, which has reduced levels of free ubiquitin, Cps1p, Phm5p and Hmx1p are mis-sorted to the vacuolar membrane. Mutation of Lys 6 in the cytoplasmic tail of Phm5p disrupts its sorting, but sorting is restored, even in doa4 cells, by the biosynthetic addition of a single ubiquitin chain. In contrast, Sna3p enters internal vesicles in a ubiquitin-independent manner. Thus, ubiquitin acts as a signal for the partitioning of some, but not all, membrane proteins into invaginating endosomal vesicles.
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PMID:Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting. 1156 81

Leptospirosis is the most widespread zoonosis worldwide and is caused by serovars of pathogenic Leptospira species. The understanding of leptospiral pathogenesis lags far behind that of many other bacterial pathogens. Current research is thus directed at identification of leptospiral virulence factors. Saprophytic Leptospira species are environmental organisms that never cause disease. Comparative genomics of pathogens and saprophytes has allowed the identification of more than 900 genes unique to either Leptospira interrogans or Leptospira borgpetersenii; these genes potentially encode virulence-associated proteins. However, genes of unknown function are over-represented in this subset of pathogen-specific genes, accounting for 80% and 60% of open reading frames, respectively. This finding, together with the absence of virulence factor homologues among the proteins of known function, suggests that Leptospira possesses unique virulence mechanisms. Whole genome microarray studies have identified genes whose expression is differentially regulated under a range of simulated in vivo conditions, such as physiological temperature and osmolarity, low iron levels, and the presence of serum. The subset of genes identified by these studies is likely to include virulence factors. However, most such genes encode proteins of unknown function, consistent with the hypothesis that leptospiral virulence genes do not have homologues in other bacterial species. The recent development of mutagenesis systems for pathogenic Leptospira spp. has allowed the screening of defined mutants for attenuation of virulence in animal infection models and has identified definitively for the first time a range of virulence factors, including lipopolysaccharide, flagella, heme oxygenase, and the OmpA-family protein, Loa22. Interestingly, inactivation of a number of genes hypothesised to encode virulence factors based on in vitro virulence-associated properties did not result in attenuation of virulence, suggesting a degree of functional redundancy in leptospiral pathogenic mechanisms.
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PMID:Pathogenesis of leptospirosis: the influence of genomics. 2144 Mar 84