Genomic structure, evolution, and expression of human FLII, a gelsolin and leucine-rich-repeat family member: overlap with LLGL.
The Drosophila melanogaster flightless-I gene is involved in cellularization processes in early embryogenesis and in the structural organization of indirect flight muscle. The encoded protein contains a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat protein-protein interaction domain. The homologous human FLII gene encodes a 1269-residue protein with 58% amino acid sequence identity and is deleted in Smith-Magenis syndrome. We have cloned the FLII gene and determined its nucleotide sequence (14.1 kb). FLII has 29 introns, compared with 13 in Caenorhabditis elegans and 3 in D. melanogaster. The positions of several introns are conserved in FLII-related genes and in the domains and subdomains of the gelsolin-like regions giving indications of gelsolin gene family evolution. In keeping with its function in indirect flight muscle in Drosophila, the human FLII gene was most highly expressed in muscle. The FLII gene lies adjacent to LLGL, the human homologue of the D. melanogaster tumor suppressor gene lethal(2) giant larvae. The 3' end of the FLII transcript overlaps the 3' end of the LLGL transcript, and the corresponding mouse genes Fliih and Llglh also overlap. The overlap region contains poly(A) signals for both genes and is strongly conserved between human and mouse.
Campbell
H D
HD
Molecular Evolution and Systematics Group, Research School of Biological Sciences, Australian National University, Canberra, Australia. Hugh.Campbell@anu.edu.au
Fountain
S
S
Young
I G
IG
Claudianos
C
C
Hoheisel
J D
JD
Chen
K S
KS
Lupski
J R
JR
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D018260:Gelsolin / Q000235:genetics*; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D007438:Introns; D007930:Leucine / Q000032:analysis; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; C098179:FLII protein, human; D018260:Gelsolin; D019476:Insect Proteins; C097906:LLGL1 protein, human; D008840:Microfilament Proteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; C098178:fliI protein, Drosophila; D007930:Leucine