Novel proteins interacting with the leucine-rich repeat domain of human flightless-I identified by the yeast two-hybrid system.
The flightless-I gene encodes a member of the gelsolin-like family of actin-binding proteins linked to a leucine-rich repeat (LRR) domain. It is required for cellularization during early embryogenesis and normal development of the indirect flight muscles in Drosophila melanogaster. Although the association between actin and the gelsolin-like domain of the human Flightless-I homologue (FLI) has been established, its biological role is unknown. The human FLI gene is mapped within the Smith-Magenis microdeletion region of chromosome 17. We report the identification of two related genes, LRRFIP1 and LRRFIP2, encoding proteins that interact with the LRR domain of human FLI using the yeast two-hybrid system. LRRFIP1 exhibits sequence identity with the TRIP RNA-binding protein and GCF-2 transcriptional repressor, which are also related to the murine FLAP-1 gene. LRRFIP2 is a novel gene that shares sequence homology with LRRFIP1 and FLAP-1. LRRFIP1 and LRRFIP2 both express alternative splice variants in heart and skeletal muscle tissue. A coiled-coil domain, conserved within each encoded protein, serves as a potential interaction motif for FLI LRR. The occurrence of multiple proteins able to interact with FLI within the same tissue suggests that they may compete for the same binding site. Sequencing and PCR-directed genomic analysis indicate that LRRFIP1 and LRRFIP2 are related genes that arose from gene duplication.
Fong
K S
KS
Department of Zoology, University of Hawaii at Manoa, Honolulu, Hawaii, 96822, USA.
de Couet
H G
HG
D048868:Adaptor Proteins, Signal Transducing; D017503:Adenovirus E3 Proteins; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D003198:Computer Simulation; D029721:Drosophila Proteins; D018260:Gelsolin; D015723:Gene Library; D006801:Humans; D019476:Insect Proteins / Q000235:genetics*; D007930:Leucine / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D035582:Transcription Factor TFIIIA
D048868:Adaptor Proteins, Signal Transducing; D017503:Adenovirus E3 Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018260:Gelsolin; D019476:Insect Proteins; C114370:LRRFIP1 protein, human; C120550:LRRFIP2 protein, human; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D035582:Transcription Factor TFIIIA; C098178:fliI protein, Drosophila; D007930:Leucine