A novel human gene encoding an F-box/WD40 containing protein maps in the SHFM3 critical region on 10q24.
We report the cloning and characterization of a new human gene, Dactylin, encoding a novel member of the F-box/WD40 protein family. The Dactylin gene comprises nine exons distributed in more than 85 kb of genomic DNA and encoding a protein with four WD40 repeats and an F-box motif. Northern blot analysis demonstrates a single 2.8 kb transcript in brain, kidney, lung and liver. FISH hybridization localized Dactylin to 10q24.3. Using an Msc I SNP identified in the first exon of the gene, we were able to assign Dactylin within the critical region for Split Hand Split Foot malformation (SHFM3) that has been mapped to 10q24. The SHFM3 phenotype includes absence or hypoplasia of the central digital rays, a deep median cleft and syndactyly of the remaining digits. Recent studies have demonstrated the importance of F-box/WD40 proteins in the regulation of developmental processes, by a mechanism of specific ubiquitinization and subsequent proteolysis of target proteins belonging to the Wnt, Hh and NF-kappaB signaling pathways. The chromosomal location of Dactylin and its putative function as an F-box/WD40 repeat protein, likely to be involved in key signaling pathways crucial for normal limb development, make it a promising candidate gene for SHFM3.
Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut, 06030, USA.
P
P
Ianakiev
M W
MW
Kilpatrick
C
C
Dealy
R
R
Kosher
J R
JR
Korenberg
X N
XN
Chen
P
P
Tsipouras
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000378:metabolism; D005091:Exons / Q000235:genetics; D020224:Expressed Sequence Tags; D044783:F-Box Proteins; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D020449:Repetitive Sequences, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics
D044783:F-Box Proteins; C120449:FBXW4 protein, human; D005819:Genetic Markers; D011506:Proteins; D012333:RNA, Messenger