title: Comprehensive classification of nucleotidyltransferase fold proteins: identification of novel families and their representatives in human.
abstract: This article presents a comprehensive review of large and highly diverse superfamily of nucleotidyltransferase fold proteins by providing a global picture about their evolutionary history, sequence-structure diversity and fulfilled functional roles. Using top-of-the-line homology detection method combined with transitive searches and fold recognition, we revised the realm of these superfamily in numerous databases of catalogued protein families and structures, and identified 10 new families of nucleotidyltransferase fold. These families include hundreds of previously uncharacterized and various poorly annotated proteins such as Fukutin/LICD, NFAT, FAM46, Mab-21 and NRAP. Some of these proteins seem to play novel important roles, not observed before for this superfamily, such as regulation of gene expression or choline incorporation into cell membrane. Importantly, within newly detected families we identified 25 novel superfamily members in human genome. Among these newly assigned members are proteins known to be involved in congenital muscular dystrophy, neurological diseases and retinal pigmentosa what sheds some new light on the molecular background of these genetic disorders. Twelve of new human nucleotidyltransferase fold proteins belong to Mab-21 family known to be involved in organogenesis and development. The determination of specific biological functions of these newly detected proteins remains a challenging task.
authors.affiliation: Laboratory of Bioinformatics and Bioengineering, Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kuchta
authors.forename: Lukasz
authors.initials: L
authors.lastname: Knizewski
authors.forename: Lucjan S
authors.initials: LS
authors.lastname: Wyrwicz
authors.forename: Leszek
authors.initials: L
authors.lastname: Rychlewski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Ginalski
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics; D009713:Nucleotidyltransferases / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012174:Retinitis Pigmentosa / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D009713:Nucleotidyltransferases