Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organophosphorus (OP) esters are known to bind covalently to the active site serine of enzymes in the serine hydrolase family. It was a surprise to find that proteins with no active site serine are also covalently modified by OP. The binding site in albumin, transferrin, and tubulin was identified as tyrosine. The goal of the present work was to determine whether binding to tyrosine is a general phenomenon. Fourteen proteins were treated with a biotin-tagged organophosphorus agent called FP-biotin. The proteins were digested with trypsin and the labeled peptides enriched by binding to monomeric avidin. Peptides were purified by HPLC and fragmented by collision induced dissociation in a tandem ion trap mass spectrometer. Eight proteins were labeled and six were not. Tyrosine was labeled in human alpha-2-glycoprotein 1 zinc-binding protein (Tyr 138, Tyr 174 and Tyr 181), human kinesin 3C motor domain (Tyr 145), human keratin 1 (Tyr 230), bovine actin (Tyr 55 and Tyr 200), murine ATP synthase beta (Tyr 431), murine adenine nucleotide translocase 1 (Tyr 81), bovine chymotrypsinogen (Tyr 201) and porcine pepsin (Tyr 310). Only 1-3 tyrosines per protein were modified, suggesting that the reactive tyrosine was activated by nearby residues that facilitated ionization of the hydroxyl group of tyrosine. These results suggest that OP binding to tyrosine is a general phenomenon. It is concluded that organophosphorus-reactive proteins include not only enzymes in the serine hydrolase family, but also proteins that have no active site serine. The recognition of a new OP-binding motif to tyrosine suggests new directions to search for mechanisms of long-term effects of OP exposure. Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered.
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PMID:Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine. 1953 7

Many anthropometric measures, including body mass index (BMI), waist-to-hip ratio (WHR), and subcutaneous fat thickness, are used as indicators of nutritional status, fertility and predictors of future health outcomes. While BMI is currently the best available estimate of body adiposity, WHR and skinfold thickness at various sites (biceps, triceps, suprailiac, and subscapular) are used as indices of body fat distribution. Copy number variation (CNV) is an attractive emerging approach to the study of associations with various diseases. In this study, we investigated the dosage effect of genes in the CNV genome widely associated with fat distribution phenotypes in large cohorts. We used the Affymetrix genome-wide human SNP Array 5.0 data of 8,842 healthy unrelated adults in KARE cohorts and identified CNVs associated with BMI and fat distribution-related traits including WHR and subcutaneous skinfold thickness at suprailiac (SUP) and subscapular (SUB) sites. CNV segmentation of each chromosome was performed using Golden Helix SVS 7.0, and single regression analysis was used to identify CNVs associated with each phenotype. We found one CNV for BMI, 287 for WHR, 2,157 for SUP, and 2,102 for SUB at the 5% significance level after Holm-Bonferroni correction. Genes included in the CNV were used for the analysis of functional annotations using the Database for Annotation, Visualization and Integrated Discovery (DAVID v6.7b) tool. Functional gene classification analysis identified five significant gene clusters (metallothionein, ATP-binding proteins, ribosomal proteins, kinesin family members, and zinc finger proteins) for SUP, three (keratin-associated proteins, zinc finger proteins, keratins) for SUB, and one (protamines) for WHR. BMI was excluded from this analysis because the entire structure of no gene was identified in the CNV. Based on the analysis of genes enriched in the clusters, the fat distribution traits of KARE cohorts were related to the fat redistribution associated with the aging process. In addition to structural variation, dosage effect analysis of genes based on CNV is useful to gain an understanding of the comprehensive biological phenomena underlying particular phenotypes and/or diseases.
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PMID:Genome-wide analysis of copy number variations reveals that aging processes influence body fat distribution in Korea Associated Resource (KARE) cohorts. 2282 14

Keratin intermediate filaments (IFs) are the major cytoskeletal component in epithelial cells. The dynamics of keratin IFs have been described to depend mostly on the actin cytoskeleton, but the rapid transport of fully polymerized keratin filaments has not been reported. In this work, we used a combination of photoconversion experiments and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 genome editing to study the role of microtubules and microtubule motors in keratin filament transport. We found that long keratin filaments, like other types of IFs, are transported along microtubules by kinesin-1. Our data revealed that keratin and vimentin are nonconventional kinesin-1 cargoes because their transport did not require kinesin light chains, which are a typical adapter for kinesin-dependent cargo transport. Furthermore, we found that the same domain of the kinesin heavy chain tail is involved in keratin and vimentin IF transport, strongly suggesting that multiple types of IFs move along microtubules using an identical mechanism.-Robert, A., Tian, P., Adam, S. A., Kittisopikul, M., Jaqaman, K., Goldman, R. D., Gelfand, V. I. Kinesin-dependent transport of keratin filaments: a unified mechanism for intermediate filament transport.
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PMID:Kinesin-dependent transport of keratin filaments: a unified mechanism for intermediate filament transport. 2994 46