FBXW4

F-box and WD repeat domain containing 4
Identifiers
Symbols	FBXW4 ; DAC; FBW4; FBWD4; SHFM3; SHSF3
External IDs	OMIM: 608071 MGI: 1354698 HomoloGene: 32197 GeneCards: FBXW4 Gene
Gene ontology Molecular function • molecular_function Cellular component • ubiquitin ligase complex Biological process • positive regulation of mesenchymal cell proliferation • ubiquitin-dependent protein catabolic process • Wnt signaling pathway • embryonic limb morphogenesis • embryonic digit morphogenesis • cartilage development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6468	30838
Ensembl	ENSG00000107829	ENSMUSG00000040913
UniProt	P57775	Q9JMJ2
RefSeq (mRNA)	NM_022039	NM_013907
RefSeq (protein)	NP_071322	NP_038935
Location (UCSC)	Chr 10: 101.61 – 101.7 Mb	Chr 19: 45.58 – 45.66 Mb
PubMed search

F-box/WD repeat-containing protein 4 is a protein that in humans is encoded by the FBXW4 gene.^[1][2][3]

This gene is a member of the F-box/WD-40 gene family, which recruit specific target proteins through their WD-40 protein-protein binding domains for ubiquitin mediated degradation. In mouse, a highly similar protein is thought to be responsible for maintaining the apical ectodermal ridge of developing limb buds; disruption of the mouse gene results in the absence of central digits, underdeveloped or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar to split hand-split foot malformation in humans, a clinically heterogeneous condition with a variety of modes of transmission. An autosomal recessive form has been mapped to the chromosomal region where this gene is located, and complex rearrangements involving duplications of this gene and others have been associated with the condition. A pseudogene of this locus has been mapped to one of the introns of the BCR gene on chromosome 22.^[3]

References

1. Gurrieri F, Prinos P, Tackels D, Kilpatrick MW, Allanson J, Genuardi M, Vuckov A, Nanni L, Sangiorgi E, Garofalo G, Nunes ME, Neri G, Schwartz C, Tsipouras P (Oct 1996). "A split hand-split foot (SHFM3) gene is located at 10q24-->25". Am J Med Genet 62 (4): 427–36. doi:10.1002/(SICI)1096-8628(19960424)62:4<427::AID-AJMG16>3.0.CO;2-Q. PMID 8723077.
2. Palmer SE, Scherer SW, Kukolich M, Wijsman EM, Tsui LC, Stephens K, Evans JP (Jul 1994). "Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation". Am J Hum Genet 55 (1): 21–6. PMC 1918225. PMID 7912888.
3. "Entrez Gene: FBXW4 F-box and WD repeat domain containing 4".

Further reading

• Ianakiev P, Kilpatrick MW, Dealy C; et al. (1999). "A novel human gene encoding an F-box/WD40 containing protein maps in the SHFM3 critical region on 10q24.". Biochem. Biophys. Res. Commun. 261 (1): 64–70. doi:10.1006/bbrc.1999.0963. PMID 10405324.
• Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (2001). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family.". Genomics 67 (1): 40–7. doi:10.1006/geno.2000.6211. PMID 10945468.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• de Mollerat XJ, Gurrieri F, Morgan CT; et al. (2004). "A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24.". Hum. Mol. Genet. 12 (16): 1959–71. doi:10.1093/hmg/ddg212. PMID 12913067.
• Basel D, DePaepe A, Kilpatrick MW, Tsipouras P (2004). "Split hand foot malformation is associated with a reduced level of Dactylin gene expression.". Clin. Genet. 64 (4): 350–4. doi:10.1034/j.1399-0004.2003.00153.x. PMID 12974740.
• Busino L, Donzelli M, Chiesa M; et al. (2003). "Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage.". Nature 426 (6962): 87–91. doi:10.1038/nature02082. PMID 14603323.
• Roscioli T, Taylor PJ, Bohlken A; et al. (2004). "The 10q24-linked split hand/split foot syndrome (SHFM3): narrowing of the critical region and confirmation of the clinical phenotype.". Am. J. Med. Genet. A 124 (2): 136–41. doi:10.1002/ajmg.a.20348. PMID 14699611.
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Deloukas P, Earthrowl ME, Grafham DV; et al. (2004). "The DNA sequence and comparative analysis of human chromosome 10.". Nature 429 (6990): 375–81. doi:10.1038/nature02462. PMID 15164054.
• Kang YS, Cheong HM, Moon Y; et al. (2004). "Molecular genetic characterization of a Korean split hand/split foot malformation (SHFM).". Mol. Cells 17 (3): 397–403. PMID 15232212.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Kano H, Kurosawa K, Horii E; et al. (2006). "Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation.". Hum. Genet. 118 (3–4): 477–83. doi:10.1007/s00439-005-0074-0. PMID 16235095.
• Everman DB, Morgan CT, Lyle R; et al. (2006). "Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non-syndromic split-hand/foot malformation". Am. J. Med. Genet. A 140 (13): 1375–83. doi:10.1002/ajmg.a.31246. PMID 16761290.