SUFU

SUFU
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1M1L, 4BL8, 4BL9, 4BLA, 4BLB, 4BLD, 4KM8, 4KM9, 4KMD, 4KMH
Identifiers
Aliases	SUFU, PRO1280, SUFUH, SUFUXL, SUFU negative regulator of hedgehog signaling, JBTS32
External IDs	OMIM: 607035; MGI: 1345643; HomoloGene: 9262; GeneCards: SUFU; OMA:SUFU - orthologs
Gene location (Human) Chr. Chromosome 10 (human) Band 10q24.32 Start 102,503,972 bp End 102,633,535 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19 C3|19 38.85 cM Start 46,385,335 bp End 46,477,243 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of arm nipple body of tongue vein stromal cell of endometrium synovial membrane mucosa of pharynx saphenous vein trigeminal ganglion internal globus pallidus Top expressed in otic vesicle seminiferous tubule saccule otic placode secondary oocyte zygote primary oocyte spermatogonium epiblast yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function beta-catenin binding transcription corepressor activity transcription factor binding signal transducer activity protein binding protein kinase binding Cellular component cytosol cilium ciliary base ciliary tip nucleus cytoplasm Biological process skeletal system development regulation of transcription, DNA-templated ventricular septum development smoothened signaling pathway involved in ventral spinal cord interneuron specification negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning spinal cord dorsal/ventral patterning negative regulation of transcription by RNA polymerase II coronary vasculature development negative regulation of DNA-binding transcription factor activity negative regulation of osteoblast differentiation proteolysis heart looping aorta development neural tube closure determination of left/right symmetry smoothened signaling pathway involved in spinal cord motor neuron cell fate specification negative regulation of ubiquitin-dependent protein catabolic process signal transduction skin development multicellular organism development cytoplasmic sequestering of transcription factor negative regulation of protein import into nucleus negative regulation of smoothened signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51684 24069 Ensembl ENSG00000107882 ENSMUSG00000025231 UniProt Q9UMX1 Q9Z0P7 RefSeq (mRNA) NM_001178133 NM_016169 NM_001025391 NM_015752 RefSeq (protein) NP_001171604 NP_057253 NP_001020562 NP_056567 Location (UCSC) Chr 10: 102.5 – 102.63 Mb Chr 19: 46.39 – 46.48 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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

• Kogerman P, Grimm T, Kogerman L, et al. (1999). "Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1". Nat. Cell Biol. 1 (5): 312–9. doi:10.1038/13031. PMID 10559945. S2CID 6907964.
• Stone DM, Murone M, Luoh S, et al. (2000). "Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli". J. Cell Sci. 112 (23): 4437–48. doi:10.1242/jcs.112.23.4437. PMID 10564661.
• Murone M, Luoh SM, Stone D, et al. (2000). "Gli regulation by the opposing activities of fused and suppressor of fused". Nat. Cell Biol. 2 (5): 310–2. doi:10.1038/35010610. PMID 10806483. S2CID 31424234.
• Delattre M, Briand S, Paces-Fessy M, Blanchet-Tournier MF (2001). "The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals". Dev. Genes Evol. 209 (5): 294–300. doi:10.1007/s004270050255. PMID 11252182. S2CID 42211231.
• Cheng SY, Bishop JM (2002). "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. Bibcode:2002PNAS...99.5442C. doi:10.1073/pnas.082096999. PMC 122788. PMID 11960000.
• Taylor MD, Liu L, Raffel C, et al. (2002). "Mutations in SUFU predispose to medulloblastoma". Nat. Genet. 31 (3): 306–10. doi:10.1038/ng916. PMID 12068298. S2CID 6882566.
• Dunaeva M, Michelson P, Kogerman P, Toftgard R (2003). "Characterization of the physical interaction of Gli proteins with SUFU proteins". J. Biol. Chem. 278 (7): 5116–22. doi:10.1074/jbc.M209492200. PMID 12426310.
• 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "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. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Paces-Fessy M, Boucher D, Petit E, et al. (2004). "The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins". Biochem. J. 378 (Pt 2): 353–62. doi:10.1042/BJ20030786. PMC 1223961. PMID 14611647.
• Taylor MD, Zhang X, Liu L, et al. (2004). "Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling". Oncogene. 23 (26): 4577–83. doi:10.1038/sj.onc.1207605. PMID 15077159.
• Deloukas P, Earthrowl ME, Grafham DV, et al. (2004). "The DNA sequence and comparative analysis of human chromosome 10". Nature. 429 (6990): 375–81. Bibcode:2004Natur.429..375D. doi:10.1038/nature02462. PMID 15164054.
• 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.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Lyle R, Radhakrishna U, Blouin JL, et al. (2006). "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. doi:10.1002/ajmg.a.31247. PMID 16691619. S2CID 24199907.

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

External links

• Eukaryotic Linear Motif resource motif class LIG_SUFU_1