Biology:SUFU

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Suppressor of fused homolog is a protein that in humans is encoded by the SUFU gene. In molecular biology, the protein domain suppressor of fused protein (Sufu) has an important role in the cell. The Sufu is important in negatively regulating an important signalling pathway in the cell, the Hedgehog signalling pathway (HH). This particular pathway is crucial in embryonic development. There are several homologues of Sufu, found in a wide variety of organisms.

Function

SUFU encodes a component of the sonic hedgehog (SHH) / patched (PTCH) signaling pathway. Mutations in genes encoding components of this pathway are deleterious for normal development and are associated with cancer-predisposing syndromes (e.g., holoprosencephaly, HPE3, basal cell nevus syndrome, BCNS, and Greig cephalopolysyndactyly syndrome, GCPS).Sufu has also been found to have a crucial role in tumour suppression. To be more specific, it has a tumour-suppressor gene that predisposes, or in other words makes individuals more susceptible to medulloblastoma, because it modulates the SHH signalling pathway. The N-terminal domain, which this entry refers to contains Gli transcription factors.

Interactions

SUFU has been shown to interact with GLI1, GLI3 and PEX26.

Conservation

The human ortholog of Drosophila suppressor of fused, has a conserved sequence, this means that particular amino acids have remained the same throughout evolution. Consequently, they have very similar roles in repressing Hedgehog signalling. It represses the Gli and Ci transcription factors of the Hedgehog pathway, and functions by binding to these proteins and preventing their translocation to the nucleus. Homologues of Sufu have been found in bacteria. However their function remains to be elucidated.

Structure

Sufu is actually protein that contains two domains. In eukaryotic Sufu, an additional domain is found at the C terminus of the protein. This protein domain also binds to the C-terminal domain of the Gli/Ci transcription factors, inhibiting their activity.

Genes

Human gene that encodes SUFU, also named SUFU, is found to be localized on chromosome 10q24–25, and contains 12 exons.

Further reading

• "Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1". Nat. Cell Biol. 1 (5): 312–9. 1999. doi:10.1038/13031. PMID 10559945. 
• "Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli". J. Cell Sci. 112 (23): 4437–48. 2000. doi:10.1242/jcs.112.23.4437. PMID 10564661. 
• "Gli regulation by the opposing activities of fused and suppressor of fused". Nat. Cell Biol. 2 (5): 310–2. 2000. doi:10.1038/35010610. PMID 10806483. 
• "The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals". Dev. Genes Evol. 209 (5): 294–300. 2001. doi:10.1007/s004270050255. PMID 11252182. 
• "Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5442–7. 2002. doi:10.1073/pnas.082096999. PMID 11960000. Bibcode: 2002PNAS...99.5442C. 
• "Mutations in SUFU predispose to medulloblastoma". Nat. Genet. 31 (3): 306–10. 2002. doi:10.1038/ng916. PMID 12068298. 
• "Characterization of the physical interaction of Gli proteins with SUFU proteins". J. Biol. Chem. 278 (7): 5116–22. 2003. doi:10.1074/jbc.M209492200. PMID 12426310. 
• "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. 2003. doi:10.1101/gr.1293003. PMID 12975309. 
• "The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins". Biochem. J. 378 (Pt 2): 353–62. 2004. doi:10.1042/BJ20030786. PMID 14611647. 
• "Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling". Oncogene 23 (26): 4577–83. 2004. doi:10.1038/sj.onc.1207605. PMID 15077159. 
• "The DNA sequence and comparative analysis of human chromosome 10". Nature 429 (6990): 375–81. 2004. doi:10.1038/nature02462. PMID 15164054. Bibcode: 2004Natur.429..375D. 
• "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334. 
• "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 
• "Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region". Am. J. Med. Genet. A 140 (13): 1384–95. 2006. doi:10.1002/ajmg.a.31247. PMID 16691619. 

This article incorporates text from the public domain Pfam and InterPro: IPR020941

External links

• Eukaryotic Linear Motif resource motif class LIG_SUFU_1