title: A novel predicted calcium-regulated kinase family implicated in neurological disorders.
abstract: The catalogues of protein kinases, the essential effectors of cellular signaling, have been charted in Metazoan genomes for a decade now. Yet, surprisingly, using bioinformatics tools, we predicted protein kinase structure for proteins coded by five related human genes and their Metazoan homologues, the FAM69 family. Analysis of three-dimensional structure models and conservation of the classic catalytic motifs of protein kinases present in four out of five human FAM69 proteins suggests they might have retained catalytic phosphotransferase activity. An EF-hand Ca(2+)-binding domain in FAM69A and FAM69B proteins, inserted within the structure of the kinase domain, suggests they may function as Ca(2+)-dependent kinases. The FAM69 genes, FAM69A, FAM69B, FAM69C, C3ORF58 (DIA1) and CXORF36 (DIA1R), are by large uncharacterised molecularly, yet linked to several neurological disorders in genetics studies. The C3ORF58 gene is found deleted in autism, and resides in the Golgi. Unusually high cysteine content and presence of signal peptides in some of the family members suggest that FAM69 proteins may be involved in phosphorylation of proteins in the secretory pathway and/or of extracellular proteins.
authors.affiliation: Warsaw University of Life Sciences, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dudkiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Lenart
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pawłowski
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001321:Autistic Disorder / Q000201:enzymology; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D016000:Cluster Analysis; D019295:Computational Biology; D017124:Conserved Sequence; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000201:enzymology*; D011494:Protein Kinases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; C585730:DIPK1A protein, human; C532314:DIPK2A protein, human; C559913:DIPK2B protein, human; D008565:Membrane Proteins; D011494:Protein Kinases