SBDS
| SBDS | |||||||||||||||||
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| Identifiers | |||||||||||||||||
| Aliases | SBDS, SDS, SWDS, CGI-97, SBDS ribosome assembly guanine nucleotide exchange factor | ||||||||||||||||
| External IDs | MGI: 1913961 HomoloGene: 6438 GeneCards: SBDS | ||||||||||||||||
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| Species | Human | Mouse | |||||||||||||||
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| RefSeq (mRNA) | |||||||||||||||||
| RefSeq (protein) | |||||||||||||||||
| Location (UCSC) | Chr 7: 66.99 – 67 Mb | Chr 5: 130.25 – 130.26 Mb | |||||||||||||||
| PubMed search | [1] | [2] | |||||||||||||||
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| View/Edit Human | View/Edit Mouse |
Ribosome maturation protein SBDS is a protein that in humans is encoded by the SBDS gene.[3] An alternative transcript has been described, but its biological nature has not been determined. This gene has a closely linked pseudogene that is distally located.[4] This gene encodes a member of a highly conserved protein family that exists from archaea to vertebrates and plants.
Function
The encoded protein may function in RNA metabolism.[4] The precise function of the SBDS protein is not known but it appears to play an important role in ribosome function or assembly.[5] Knockdown of SBDS expression results in increased apoptosis in erythroid cells undergoing differentiation due to elevated ROS levels. Hence SBDS is critical for normal erythropoiesis.[6]
This family is highly conserved in species ranging from archaea to vertebrates and plants. The family contains several Shwachman-Bodian-Diamond syndrome (SBDS) proteins from both mouse and humans. Shwachman-Diamond syndrome is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. Members of this family play a role in RNA metabolism.[3][7]
A number of uncharacterised hydrophilic proteins of about 30 kDa share regions of similarity. These include,
- Mouse protein 22A3.
- Saccharomyces cerevisiae chromosome XII hypothetical protein YLR022c.
- Caenorhabditis elegans hypothetical protein W06E11.4.
- Methanococcus jannaschii hypothetical protein MJ0592.
This particular protein sequence is highly conserved in species ranging from archaea to vertebrates and plants.[3]
Structure
The SBDS protein contains three domains, an N-terminal conserved FYSH domain, central helical domain and C-terminal domain containing an RNA-binding motif.[5]
SBDS N-terminal domain
| SBDS protein N-terminal domain | |||||||||
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| Identifiers | |||||||||
| Symbol | SBDS | ||||||||
| Pfam | PF01172 | ||||||||
| InterPro | IPR019783 | ||||||||
| PROSITE | PDOC00974 | ||||||||
| SCOP | 1nyn | ||||||||
| SUPERFAMILY | 1nyn | ||||||||
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Function
This protein domain appears to be very important, since mutations in this domain are usually the cause of Shwachman-Bodian-Diamond syndrome. It shares distant structural and sequence homology to a protein named YHR087W found in the yeast Saccharomyces cerevisiae. The protein YHR087W is involved in RNA metabolism, so it is probable that the SBDS N-terminal domain has the same function.[7]
Structure
The N-terminal domains contains a novel mixed alphabeta fold, four beta-strands, and four alpha-helices arranged as a three beta stranded anti-parallel-sheet.[7]
SBDS central domain
Function
The function of this protein domain has been difficult to elucidate. It is possible that it has a role in binding to DNA or RNA. Protein binding to form a protein complex is also another possibility. It has been difficult to infer the function from the structure since this particular domain structure is found in archea.[7]
Structure
This domain contains a very common structure, the winged helix-turn-helix.[7]
SBDS C-terminal domain
| SBDS protein C-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | SBDS_C | ||||||||
| Pfam | PF09377 | ||||||||
| InterPro | IPR018978 | ||||||||
| SCOP | 1nyn | ||||||||
| SUPERFAMILY | 1nyn | ||||||||
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In molecular biology, the SBDS C-terminal protein domain is highly conserved in species ranging from archaea to vertebrates and plants.[8]
Function
Members of this family are thought to play a role in RNA metabolism.[7] However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.[7]
Structure
The structure of the C-terminal domain contains a ferredoxin-like fold[9] This structure has a four-stranded beta-sheet with two helices on one side.[7]
Clinical significance
Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome .[4] The two most common mutations associated with this syndrome are at positions 183–184 (TA→CT) resulting in a premature stop-codon (K62X) and a frameshift mutation at position 258 (2T→C) resulting in a stopcodon (C84fsX3).[5]
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- 1 2 3 Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM (Jan 2003). "Mutations in SBDS are associated with Shwachman-Diamond syndrome". Nat Genet. 33 (1): 97–101. doi:10.1038/ng1062. PMID 12496757.
- 1 2 3 "Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome".
- 1 2 3 Orelio C, van der Sluis RM, Verkuijlen P, Nethe M, Hordijk PL, van den Berg TK, Kuijpers TW (2011). "Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome". PLoS ONE. 6 (6): e20727. doi:10.1371/journal.pone.0020727. PMC 3113850
. PMID 21695142. - ↑ Sen S, Wang H, Nghiem CL, Zhou K, Yau J, Tailor CS, Irwin MS, Dror Y (December 2011). "The ribosome-related protein, SBDS, is critical for normal erythropoiesis". Blood. 118 (24): 6407–17. doi:10.1182/blood-2011-02-335190. PMID 21963601.
- 1 2 3 4 5 6 7 8 Savchenko A, Krogan N, Cort JR, Evdokimova E, Lew JM, Yee AA, Sánchez-Pulido L, Andrade MA, Bochkarev A, Watson JD, Kennedy MA, Greenblatt J, Hughes T, Arrowsmith CH, Rommens JM, Edwards AM (May 2005). "The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism". J. Biol. Chem. 280 (19): 19213–20. doi:10.1074/jbc.M414421200. PMID 15701634.
- ↑ Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM (January 2003). "Mutations in SBDS are associated with Shwachman-Diamond syndrome". Nat. Genet. 33 (1): 97–101. doi:10.1038/ng1062. PMID 12496757.
- ↑ Shammas C, Menne TF, Hilcenko C, Michell SR, Goyenechea B, Boocock GR, et al. (2005). "Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome.". J Biol Chem. 280 (19): 19221–9. doi:10.1074/jbc.M414656200. PMID 15701631.
Further reading
- Lai CH, Chou CY, Ch'ang LY, et al. (2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.". Genome Res. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC 310876. PMID 10810093.
- Popovic M, Goobie S, Morrison J, et al. (2002). "Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene.". Eur. J. Hum. Genet. 10 (4): 250–8. doi:10.1038/sj.ejhg.5200798. PMID 12032733.
- 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.
- 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.
- Nakashima E, Mabuchi A, Makita Y, et al. (2004). "Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.". Hum. Genet. 114 (4): 345–8. doi:10.1007/s00439-004-1081-2. PMID 14749921.
- Woloszynek JR, Rothbaum RJ, Rawls AS, et al. (2004). "Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome.". Blood. 104 (12): 3588–90. doi:10.1182/blood-2004-04-1516. PMID 15284109.
- 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.
- Andersen JS, Lam YW, Leung AK, et al. (2005). "Nucleolar proteome dynamics.". Nature. 433 (7021): 77–83. doi:10.1038/nature03207. PMID 15635413.
- Kuijpers TW, Alders M, Tool AT, et al. (2005). "Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship.". Blood. 106 (1): 356–61. doi:10.1182/blood-2004-11-4371. PMID 15769891.
- Austin KM, Leary RJ, Shimamura A (2005). "The Shwachman-Diamond SBDS protein localizes to the nucleolus.". Blood. 106 (4): 1253–8. doi:10.1182/blood-2005-02-0807. PMC 1895203. PMID 15860664.
- Kawakami T, Mitsui T, Kanai M, et al. (2005). "Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations.". Tohoku J. Exp. Med. 206 (3): 253–9. doi:10.1620/tjem.206.253. PMID 15942154.
- Boocock GR, Marit MR, Rommens JM (2006). "Phylogeny, sequence conservation, and functional complementation of the SBDS protein family.". Genomics. 87 (6): 758–71. doi:10.1016/j.ygeno.2006.01.010. PMID 16529906.
- Erdos M, Alapi K, Balogh I, et al. (2007). "Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene.". Exp. Hematol. 34 (11): 1517–21. doi:10.1016/j.exphem.2006.06.009. PMID 17046571.
- Nishimura G, Nakashima E, Hirose Y, et al. (2007). "The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type.". J. Med. Genet. 44 (4): e73. doi:10.1136/jmg.2006.043869. PMC 2598034. PMID 17400792.
- Calado RT, Graf SA, Wilkerson KL, et al. (2007). "Mutations in the SBDS gene in acquired aplastic anemia.". Blood. 110 (4): 1141–6. doi:10.1182/blood-2007-03-080044. PMC 1939897. PMID 17478638.
- Wang Y, Yagasaki H, Hama A, et al. (2007). "Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children.". Haematologica. 92 (11): 1573. doi:10.3324/haematol.11568. PMID 18024409.
External links
This article incorporates text from the public domain Pfam and InterPro IPR002140