Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly.
The mammalian translation initiation factor 3 (eIF3), is a multiprotein complex of approximately 600 kDa that binds to the 40 S ribosome and promotes the binding of methionyl-tRNAi and mRNA. cDNAs encoding 5 of the 10 subunits, namely eIF3-p170, -p116, -p110, -p48, and -p36, have been isolated previously. Here we report the cloning and characterization of human cDNAs encoding the major RNA binding subunit, eIF3-p66, and two additional subunits, eIF3-p47 and eIF3-p40. Each of these proteins is present in immunoprecipitates formed with affinity-purified anti-eIF3-p170 antibodies. Human eIF3-p66 shares 64% sequence identity with a hypothetical Caenorhabditis elegans protein, presumably the p66 homolog. Deletion analyses of recombinant derivatives of eIF3-p66 show that the RNA-binding domain lies within an N-terminal 71-amino acid region rich in lysine and arginine. The N-terminal regions of human eIF3-p40 and eIF3-p47 are related to each other and to 17 other eukaryotic proteins, including murine Mov-34, a subunit of the 26 S proteasome. Phylogenetic analyses of the 19 related protein sequences, called the Mov-34 family, distinguish five major subgroups, where eIF3-p40, eIF3-p47, and Mov-34 are each found in a different subgroup. The subunit composition of eIF3 appears to be highly conserved in Drosophila melanogaster, C. elegans, and Arabidopsis thaliana, whereas only 5 homologs of the 10 subunits of mammalian eIF3 are encoded in S. cerevisiae.
Asano
K
K
Department of Biological Chemistry, School of Medicine, University of California, Davis, California 95616, USA.
Vornlocher
H P
HP
Richter-Cook
N J
NJ
Merrick
W C
WC
Hinnebusch
A G
AG
Hershey
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D039621:Eukaryotic Initiation Factor-3; D019143:Evolution, Molecular; D005260:Female; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D046912:Multiprotein Complexes; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry; D010448:Peptide Initiation Factors / Q000096:biosynthesis* / Q000737:chemistry*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D039621:Eukaryotic Initiation Factor-3; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D010448:Peptide Initiation Factors; D012333:RNA, Messenger