FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2134745259> ?p ?o ?g. }

• W2134745259 endingPage "69" @default.
• W2134745259 startingPage "69" @default.
• W2134745259 abstract "The human genome contains a large number of gene clusters with multiple-variable-first exons, including the drug-metabolizing UDP glucuronosyltransferase (UGT1) and I-branching β-1,6-N-acetylglucosaminyltransferase (GCNT2, also known as IGNT) clusters, organized in a tandem array, similar to that of the protocadherin (PCDH), immunoglobulin (IG), and T-cell receptor (TCR) clusters. To gain insight into the evolutionary processes that may have shaped their diversity, we performed comprehensive comparative analyses for vertebrate multiple-variable-first-exon clusters. We found that there are species-specific variable-exon duplications and mutations in the vertebrate Ugt1, Gcnt2, and Ugt2a clusters and that their variable and constant genomic organizations are conserved and vertebrate-specific. In addition, analyzing the complete repertoires of closely-related Ugt2 clusters in humans, mice, and rats revealed extensive lineage-specific duplications. In contrast to the Pcdh gene clusters, gene conversion does not play a predominant role in the evolution of the vertebrate Ugt1, Gcnt2 and Ugt2 gene clusters. Thus, their tremendous diversity is achieved through birth-and-death evolution. Comparative analyses and homologous modeling demonstrated that vertebrate UGT proteins have similar three-dimensional structures each with N-terminal and C-terminal Rossmann-fold domains binding acceptor and donor substrates, respectively. Molecular docking experiments identified key residues in donor and acceptor recognition and provided insight into the catalytic mechanism of UGT glucuronidation, suggesting the human UGT1A1 residue histidine 39 (H39) as a general base and the residue aspartic acid 151 (D151) as an important electron-transfer helper. In addition, we identified four hypervariable regions in the N-terminal Rossmann domain that form an acceptor-binding pocket. Finally, analyzing patterns of nonsynonymous and synonymous nucleotide substitutions identified codon sites that are subject to positive Darwinian selection at the molecular level. These diversified residues likely play an important role in recognition of myriad xenobiotics and endobiotics. Our results suggest that enormous diversity of vertebrate multiple variable first exons is achieved through birth-and-death evolution and that adaptive evolution of specific codon sites enhances vertebrate UGT diversity for defense against environmental agents. Our results also have interesting implications regarding the staggering molecular diversity required for chemical detoxification and drug clearance." @default.
• W2134745259 created "2016-06-24" @default.
• W2134745259 creator A5011065863 @default.
• W2134745259 creator A5068836221 @default.
• W2134745259 date "2007-01-01" @default.
• W2134745259 modified "2023-09-23" @default.
• W2134745259 title "Adaptive evolution of multiple-variable exons and structural diversity of drug-metabolizing enzymes" @default.
• W2134745259 cites W1497837463 @default.
• W2134745259 cites W1509216111 @default.
• W2134745259 cites W1572023751 @default.
• W2134745259 cites W1584051659 @default.
• W2134745259 cites W1585595042 @default.
• W2134745259 cites W186326386 @default.
• W2134745259 cites W1970809419 @default.
• W2134745259 cites W1977950017 @default.
• W2134745259 cites W1984316285 @default.
• W2134745259 cites W1989228404 @default.
• W2134745259 cites W1989245196 @default.
• W2134745259 cites W1991344372 @default.
• W2134745259 cites W1998300401 @default.
• W2134745259 cites W2000170549 @default.
• W2134745259 cites W2000777444 @default.
• W2134745259 cites W2002127364 @default.
• W2134745259 cites W2004441139 @default.
• W2134745259 cites W2009376203 @default.
• W2134745259 cites W2013920609 @default.
• W2134745259 cites W2015566312 @default.
• W2134745259 cites W2015642465 @default.
• W2134745259 cites W2020869819 @default.
• W2134745259 cites W2022190511 @default.
• W2134745259 cites W2025056076 @default.
• W2134745259 cites W2029377282 @default.
• W2134745259 cites W2029993034 @default.
• W2134745259 cites W2035066314 @default.
• W2134745259 cites W2048912867 @default.
• W2134745259 cites W2049089966 @default.
• W2134745259 cites W2050456292 @default.
• W2134745259 cites W2052481299 @default.
• W2134745259 cites W2056384440 @default.
• W2134745259 cites W2056927502 @default.
• W2134745259 cites W2057457240 @default.
• W2134745259 cites W2059890422 @default.
• W2134745259 cites W2061587734 @default.
• W2134745259 cites W2063990241 @default.
• W2134745259 cites W2068126682 @default.
• W2134745259 cites W2070692993 @default.
• W2134745259 cites W2074222872 @default.
• W2134745259 cites W2074961888 @default.
• W2134745259 cites W2079565853 @default.
• W2134745259 cites W2080956086 @default.
• W2134745259 cites W2081831722 @default.
• W2134745259 cites W2082287966 @default.
• W2134745259 cites W2083624847 @default.
• W2134745259 cites W2084805548 @default.
• W2134745259 cites W2093915500 @default.
• W2134745259 cites W2094962946 @default.
• W2134745259 cites W2095708925 @default.
• W2134745259 cites W2096275360 @default.
• W2134745259 cites W2102122585 @default.
• W2134745259 cites W2109258478 @default.
• W2134745259 cites W2111441225 @default.
• W2134745259 cites W2111897112 @default.
• W2134745259 cites W2114520383 @default.
• W2134745259 cites W2118025286 @default.
• W2134745259 cites W2119632499 @default.
• W2134745259 cites W2128296317 @default.
• W2134745259 cites W2130988208 @default.
• W2134745259 cites W2132804094 @default.
• W2134745259 cites W2133027506 @default.
• W2134745259 cites W2135716823 @default.
• W2134745259 cites W2138995036 @default.
• W2134745259 cites W2143022766 @default.
• W2134745259 cites W2143330845 @default.
• W2134745259 cites W2145327188 @default.
• W2134745259 cites W2149352606 @default.
• W2134745259 cites W2151031764 @default.
• W2134745259 cites W2153187042 @default.
• W2134745259 cites W2154179549 @default.
• W2134745259 cites W2155305442 @default.
• W2134745259 cites W2158266834 @default.
• W2134745259 cites W2159146649 @default.
• W2134745259 cites W2159558922 @default.
• W2134745259 cites W2161069288 @default.
• W2134745259 cites W2170288714 @default.
• W2134745259 cites W2171022989 @default.
• W2134745259 cites W2172276670 @default.
• W2134745259 cites W2333157220 @default.
• W2134745259 doi "https://doi.org/10.1186/1471-2148-7-69" @default.
• W2134745259 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1885805" @default.
• W2134745259 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17475008" @default.
• W2134745259 hasPublicationYear "2007" @default.
• W2134745259 type Work @default.
• W2134745259 sameAs 2134745259 @default.
• W2134745259 citedByCount "40" @default.
• W2134745259 countsByYear W21347452592012 @default.
• W2134745259 countsByYear W21347452592013 @default.
• W2134745259 countsByYear W21347452592014 @default.
• W2134745259 countsByYear W21347452592015 @default.

• next