Summary: SBDS protein C-terminal domain
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SBDS Edit Wikipedia article
Ribosome maturation protein SBDS is a protein that in humans is encoded by the SBDS gene.[2] 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.[3] This gene encodes a member of a highly conserved protein family that exists from archaea to vertebrates and plants.
Contents
Function
The encoded protein may function in RNA metabolism.[3] The precise function of the SBDS protein is not known but it appears to play an important role in ribosome function or assembly.[4] 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.[5]
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.[2][6]
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.[2]
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.[4]
SBDS N-terminal domain
| SBDS protein N-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| 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.[6]
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.[6]
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.[6]
Structure
This domain contains a very common structure, the winged helix-turn-helix.[6]
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.[7]
Function
Members of this family are thought to play a role in RNA metabolism.[6] However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.[6]
Structure
The structure of the C-terminal domain contains a ferredoxin-like fold[8] This structure has a four-stranded beta-sheet with two helices on one side.[6]
Clinical significance
Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome .[3] 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).[4]
References
- ^ PDB 2L9NFinch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, González Fernández A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanné-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ (May 2011). "Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome". Genes Dev. 25 (9): 917–29. doi:10.1101/gad.623011. PMC 3084026. PMID 21536732.
- ^ a b c 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.
- ^ a b c "Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome".
- ^ a b c 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.
- ^ a b c d e f g h 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
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
SBDS protein C-terminal domain Provide feedback
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 [2] [3].
Literature references
-
Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM; , Nat Genet 2003;33:97-101.: Mutations in SBDS are associated with Shwachman-Diamond syndrome. PUBMED:12496757 EPMC:12496757
-
Savchenko A, Krogan N, Cort JR, Evdokimova E, Lew JM, Yee AA, Sanchez-Pulido L, Andrade MA, Bochkarev A, Watson JD, Kennedy MA, Greenblatt J, Hughes T, Arrowsmith CH, Rommens JM, Edwards AM; , J Biol Chem 2005; [Epub ahead of print]: The SHWACHMAN-Bodian-diamond syndromeprotein family is involved in RNA metabolism. PUBMED:15701634 EPMC:15701634
-
Shammas C, Menne TF, Hilcenko C, Michell SR, Goyenechea B, Boocock GR, Durie PR, Rommens JM, Warren AJ; , J Biol Chem 2005; [Epub ahead of print]: Structural and mutational analysis of the SBDS protein family: insight into the leukemia-associated shwachman-diamond syndrome. PUBMED:15701631 EPMC:15701631
External database links
| PANDIT: | PF09377 |
| Pseudofam: | PF09377 |
| SCOP: | 1nyn |
| SYSTERS: | SBDS_C |
This tab holds annotation information from the InterPro database.
InterPro entry IPR018978
This entry represents the C-terminal domain of proteins that are highly conserved in species ranging from archaea to vertebrates and plants [PUBMED:12496757]. The family contains several Shwachman-Bodian-Diamond syndrome (SBDS, OMIM 260400) 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. It is characterised by bone marrow failure and leukemia predisposition. Members of this family play a role in RNA metabolism [PUBMED:15701631, PUBMED:15701634]. In yeast Sdo1 is involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with the EF-2-like GTPase RIA1 (EfI1), it triggers the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating TIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. This data links defective late 60S subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition [PUBMED:17353896].
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.
- Methanocaldococcus jannaschii (Methanococcus jannaschii) hypothetical protein MJ0592.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Biological process | ribosome biogenesis (GO:0042254) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan EF-G_C (CL0437), which has the following description:
This superfamily is characterised by being an alpha-beta 2-Layer Sandwich. It is found in EF2 proteins from both prokaryotes and eukaryotes, as well as in some tetracycline resistance proteins, peptide chain release factors ], and in the C-terminal region of the bacterial hypothetical protein, YigZ.
The clan contains the following 4 members:
DUF1949 EFG_C EFG_II SBDS_CAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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| Seed (27) |
Full (515) |
Representative proteomes | NCBI (502) |
Meta (98) |
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|---|---|---|---|---|---|---|---|---|
| RP15 (114) |
RP35 (198) |
RP55 (282) |
RP75 (343) |
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| Jalview | ||||||||
| HTML | ||||||||
| PP/heatmap | 1 | |||||||
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| Seed (27) |
Full (515) |
Representative proteomes | NCBI (502) |
Meta (98) |
||||
|---|---|---|---|---|---|---|---|---|
| RP15 (114) |
RP35 (198) |
RP55 (282) |
RP75 (343) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Bateman A |
| Previous IDs: | none |
| Type: | Domain |
| Author: | Bateman A |
| Number in seed: | 27 |
| Number in full: | 515 |
| Average length of the domain: | 134.40 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 49.03 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 125 | ||||||||||||
| Family (HMM) version: | 5 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Unclassified sequence
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Interactions
There is 1 interaction for this family. More...
SBDSStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SBDS_C domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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