Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphorylation of glucose, a crucial step in cellular metabolism, is catalysed by hexokinases (HK), of which there are four (HKI-IV) in mammalian tissues. The brain HK, (HK1), like HKII and HKIII, has a molecular weight of approximately 100 kDa. HKII is insulin-sensitive and found in adipose and muscle cells. HKIV, also known as glucokinase, has a molecular weight of 50 kDa and is specific to liver and pancreas. Most brain HK is bound to mitochondria via porins, enabling coordination between glucose consumption and oxidation. Tumour cells are known to be highly glycolytic, and correspondingly increased expression of glycolytic enzymes, including HK, have been detected in resected tumours from patients with lung, gastrointestinal and breast cancer. In the latter group, further increases in HK activity were associated with metastatic disease. Some studies have demonstrated increased HK activity in renal tumours, and also have reported changes in the isoenzymic expression of HK. Experimental studies of the initiation and progression of liver tumours have demonstrated a shift in expression from that of HKIV to HKI and HKII, with increased HK binding to mitochondria and a > 100-fold increase in HK activity. However, studies using xenografts derived from gliomas found decreased HK activity corresponding with loss of chromosome 10, the carrier of the HKI gene. Compared with normal tissues, a number of mechanisms are associated with changes in HK activity seen in tumours of the liver and other sites, and these include HK gene dosage, increased transcription, modulation of HK promoter activity by a broader range of effectors, and increased mitochondrial binding of HK. Increased HK activity, together with increased glucose transport by tumour cells, has been exploited in cancer imaging using the positron-labelled glucose analogue (18F)fluoro-2-deoxy-D-glucose (FDG), which is transported into cells and then phosphorylated, but undergoes little further metabolism. Accumulated FDG then can be detected using positron emission tomography (PET).
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PMID:Mammalian hexokinases and their abnormal expression in cancer. 1091 95

One of the hallmarks of cancer is the change of energy metabolism, mainly activation of glycolysis that occurs even at early stages of tumorigenesis. The glycolysis activation can be caused by overexpression of hexokinases, primarily HK1 and HK2. Colorectal cancer, which takes the third place in the cancer morbidity and mortality rates worldwide, is believed to be accompanied with overexpression of HK2, which is .considered a marker of poor prognosis. With the use of the developed CrossHub tool, we performed the analysis of the Cancer Genome Atlas RNA-Sequencing data, which, on the contrary, revealed the prevalence of the down-regulation of HK2 gene and only slight expression alterations in HK1 gene. The Cancer Genome Atlas is the largest resource in the field of molecular oncology that accumulated genomic, transcriptomic and methylomic data for thousands of sample of more than 20 cancers. The transcriptome analysis data for colorectal cancer (283 tumor samples and 41 matched normal samples) were in accord with the results of further qPCR expression level evaluation. Up-regulation of HK1 and HK2 genes was observed only in a part of samples: 12% for HK1 and 30% for HK2. At the same time, the HK2 mRNA level decrease was shown in 50% of cases. Correlation analysis revealed the consistency in HK1 and HK2 expression alterations (Spearman's rank correlation coefficient r(s) = 0.43, p < 0.01), that could be explained by common deregulation mechanisms of these genes in colorectal tumors. The HK3 expression level was significantly increased in 60% of samples. Most likely, just hexokinase 3 contributes significantly to the activation of glycolysis in colorectal cancer.
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PMID:[Evaluation of Gene Expression of Hexokinases in Colorectal Cancer with the Use of Bioinformatics Methods]. 2685 92

Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIII-containing genomes also contain pilT, a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design.IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.
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PMID:Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility. 2848 44