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{{Infobox_gene}}
{{PBB_Controls
'''Ribosome maturation protein SBDS''' is a [[protein]] that in humans is encoded by the ''SBDS'' [[gene]].<ref name="Boocock_2003">{{cite journal | vauthors = Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM | title = Mutations in SBDS are associated with Shwachman-Diamond syndrome | journal = Nat Genet | volume = 33 | issue = 1 | pages = 97–101 |date=Jan 2003 | pmid = 12496757 | pmc =  | doi = 10.1038/ng1062 }}</ref> 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.<ref name="entrez">{{cite web | title = Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51119| accessdate = }}</ref> This gene encodes a member of a highly conserved protein family that exists from archaea to vertebrates and plants.
| update_page = yes
 
| require_manual_inspection = no
== Function ==
| update_protein_box = yes
 
| update_summary = yes
The encoded protein may function in RNA metabolism.<ref name="entrez" /> The precise function of the SBDS protein is not known but it appears to play an important role in [[ribosome]] function or assembly.<ref name="Orelio_2011">{{cite journal | vauthors = Orelio C, van der Sluis RM, Verkuijlen P, Nethe M, Hordijk PL, van den Berg TK, Kuijpers TW | title = Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome | journal = PLoS ONE | volume = 6 | issue = 6 | pages = e20727 | year = 2011 | pmid = 21695142 | pmc = 3113850 | doi = 10.1371/journal.pone.0020727 }}</ref> [[Gene knockdown|Knockdown]] of SBDS expression results in increased [[apoptosis]] in [[erythroid]] cells undergoing [[cellular differentiation|differentiation]] due to elevated [[reactive oxygen species|ROS]] levels. Hence SBDS is critical for normal [[erythropoiesis]].<ref name="pmid21963601">{{cite journal | vauthors = Sen S, Wang H, Nghiem CL, Zhou K, Yau J, Tailor CS, Irwin MS, Dror Y | title = The ribosome-related protein, SBDS, is critical for normal erythropoiesis | journal = Blood | volume = 118 | issue = 24 | pages = 6407–17 |date=December 2011 | pmid = 21963601 | doi = 10.1182/blood-2011-02-335190  }}</ref>
| update_citations = yes
 
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.<ref name="Boocock_2003"/><ref name="pmid15701634">{{cite journal | vauthors = 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 | title = The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism | journal = J. Biol. Chem. | volume = 280 | issue = 19 | pages = 19213–20 |date=May 2005 | pmid = 15701634 | doi = 10.1074/jbc.M414421200 }}</ref>
 
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 [[Conservation (genetics)|highly conserved]] in [[species]] ranging from [[archaea]] to [[vertebrates]] and [[plants]].<ref name="Boocock_2003"/>
 
== 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.<ref name="Orelio_2011"/>
 
== SBDS N-terminal domain ==
{{Infobox protein family|align=left
| Symbol = SBDS
| Name = SBDS protein N-terminal domain
| image =
| width =
| caption =
| Pfam = PF01172
| Pfam_clan =
| InterPro = IPR019783
| SMART =
| PROSITE = PDOC00974
| MEROPS =
| SCOP = 1nyn
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
===Function===
{{GNF_Protein_box
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.<ref name="pmid15701634" />
| image =
 
| image_source =
===Structure===
| PDB =  
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.<ref name="pmid15701634" />
| Name = Shwachman-Bodian-Diamond syndrome
 
| HGNCid = 19440
{{clear left}}
| Symbol = SBDS
 
| AltSymbols =; SDS; CGI-97; FLJ10917; SWDS
==SBDS central domain==
| OMIM = 607444
 
| ECnumber =
===Function===
| Homologene = 6438
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]].<ref name="pmid15701634" />
| MGIid = 1913961
 
| Function =  
===Structure===
| Component =  
This domain contains a very common structure, the winged [[helix-turn-helix]].<ref name="pmid15701634" />
| Process =  
 
| Orthologs = {{GNF_Ortholog_box
== SBDS C-terminal domain ==
    | Hs_EntrezGene = 51119
{{Pfam_box|align=none
    | Hs_Ensembl = ENSG00000126524
| Symbol = SBDS_C
    | Hs_RefseqProtein = NP_057122
| Name = SBDS protein C-terminal domain
    | Hs_RefseqmRNA = NM_016038
| image =
    | Hs_GenLoc_db =
| width =
    | Hs_GenLoc_chr = 7
| caption =
    | Hs_GenLoc_start = 66090125
| Pfam = PF09377
    | Hs_GenLoc_end = 66098023
| InterPro = IPR018978
    | Hs_Uniprot = Q9Y3A5
| SMART=
    | Mm_EntrezGene = 66711
| Prosite =
    | Mm_Ensembl = ENSMUSG00000025337
| SCOP = 1nyn
    | Mm_RefseqmRNA = NM_023248
| TCDB =
    | Mm_RefseqProtein = NP_075737
| OPM family=
    | Mm_GenLoc_db =
| OPM protein=
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 130530438
    | Mm_GenLoc_end = 130540169
    | Mm_Uniprot = P70122
  }}
}}
}}
'''Shwachman-Bodian-Diamond syndrome''', also known as '''SBDS''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51119| accessdate = }}</ref>
In [[molecular biology]], the '''SBDS [[C-terminal]]''' [[protein domain]] is [[Conservation (genetics)|highly conserved]] in [[species]] ranging from [[archaea]] to [[vertebrates]] and [[plants]].<ref name="pmid12496757">{{cite journal | vauthors = Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM | title = Mutations in SBDS are associated with Shwachman-Diamond syndrome | journal = Nat. Genet. | volume = 33 | issue = 1 | pages = 97–101 |date=January 2003 | pmid = 12496757 | doi = 10.1038/ng1062 | url = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
===Function===
{{PBB_Summary
Members of this family are thought to play a role in RNA [[metabolism#Regulation and control|metabolism]].<ref name="pmid15701634" /> However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.<ref name="pmid15701634" />
| section_title =  
 
| summary_text = This gene encodes a member of a highly conserved protein family that exists from archaea to vertebrates and plants. The encoded protein may function in RNA metabolism. Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome. 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.<ref name="entrez">{{cite web | title = Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51119| accessdate = }}</ref>
===Structure===
}}
The structure of the C-terminal domain contains a ferredoxin-like fold<ref name="pmid15701631">{{cite journal |vauthors=Shammas C, Menne TF, Hilcenko C, Michell SR, Goyenechea B, Boocock GR, etal | title=Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome. | journal=J Biol Chem | year= 2005 | volume= 280 | issue= 19 | pages= 19221–9 | pmid=15701631 | doi=10.1074/jbc.M414656200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15701631  }}</ref> This structure has a four-stranded [[beta-sheet]] with two [[alpha helix|helices]] on one side.<ref name="pmid15701634" />
 
== Clinical significance ==
 
Mutations within this gene are associated with {{SWL|type=mutations_associated_to|target=Shwachman-Bodian-Diamond syndrome|label=Shwachman-Bodian-Diamond syndrome}}.<ref name="entrez" /> 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).<ref name="Orelio_2011"/>
 
== References ==
{{reflist|35em}}


==References==
== Further reading ==
{{reflist|2}}
{{refbegin|35em}}
==Further reading==
*{{cite journal   |vauthors=Lai CH, Chou CY, Ch'ang LY, etal |title=Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. |journal=Genome Res. |volume=10 |issue= 5 |pages= 703–13 |year= 2000 |pmid= 10810093 |doi= 10.1101/gr.10.5.703| pmc=310876 }}
{{refbegin | 2}}
*{{cite journal   |vauthors=Popovic M, Goobie S, Morrison J, etal |title=Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene. |journal=Eur. J. Hum. Genet. |volume=10 |issue= 4 |pages= 250–8 |year= 2002 |pmid= 12032733 |doi= 10.1038/sj.ejhg.5200798 }}
{{PBB_Further_reading
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
| citations =
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Lai CH, Chou CY, Ch'ang LY, ''et al.'' |title=Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. |journal=Genome Res. |volume=10 |issue= 5 |pages= 703-13 |year= 2000 |pmid= 10810093 |doi=  }}
*{{cite journal   |vauthors=Nakashima E, Mabuchi A, Makita Y, etal |title=Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome. |journal=Hum. Genet. |volume=114 |issue= 4 |pages= 345–8 |year= 2004 |pmid= 14749921 |doi= 10.1007/s00439-004-1081-2 }}
*{{cite journal | author=Popovic M, Goobie S, Morrison J, ''et al.'' |title=Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene. |journal=Eur. J. Hum. Genet. |volume=10 |issue= 4 |pages= 250-8 |year= 2002 |pmid= 12032733 |doi= 10.1038/sj.ejhg.5200798 }}
*{{cite journal   |vauthors=Woloszynek JR, Rothbaum RJ, Rawls AS, etal |title=Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome. |journal=Blood |volume=104 |issue= 12 |pages= 3588–90 |year= 2004 |pmid= 15284109 |doi= 10.1182/blood-2004-04-1516 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal | author=Boocock GR, Morrison JA, Popovic M, ''et al.'' |title=Mutations in SBDS are associated with Shwachman-Diamond syndrome. |journal=Nat. Genet. |volume=33 |issue= 1 |pages= 97-101 |year= 2003 |pmid= 12496757 |doi= 10.1038/ng1062 }}
*{{cite journal   |vauthors=Andersen JS, Lam YW, Leung AK, etal |title=Nucleolar proteome dynamics. |journal=Nature |volume=433 |issue= 7021 |pages= 77–83 |year= 2005 |pmid= 15635413 |doi= 10.1038/nature03207 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal   |vauthors=Kuijpers TW, Alders M, Tool AT, etal |title=Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship. |journal=Blood |volume=106 |issue= 1 |pages= 356–61 |year= 2005 |pmid= 15769891 |doi= 10.1182/blood-2004-11-4371 }}
*{{cite journal | author=Nakashima E, Mabuchi A, Makita Y, ''et al.'' |title=Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome. |journal=Hum. Genet. |volume=114 |issue= 4 |pages= 345-8 |year= 2004 |pmid= 14749921 |doi= 10.1007/s00439-004-1081-2 }}
*{{cite journal  | vauthors=Austin KM, Leary RJ, Shimamura A |title=The Shwachman-Diamond SBDS protein localizes to the nucleolus. |journal=Blood |volume=106 |issue= 4 |pages= 1253–8 |year= 2005 |pmid= 15860664 |doi= 10.1182/blood-2005-02-0807 | pmc=1895203 }}
*{{cite journal | author=Woloszynek JR, Rothbaum RJ, Rawls AS, ''et al.'' |title=Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome. |journal=Blood |volume=104 |issue= 12 |pages= 3588-90 |year= 2004 |pmid= 15284109 |doi= 10.1182/blood-2004-04-1516 }}
*{{cite journal   |vauthors=Kawakami T, Mitsui T, Kanai M, etal |title=Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations. |journal=Tohoku J. Exp. Med. |volume=206 |issue= 3 |pages= 253–9 |year= 2005 |pmid= 15942154 |doi=10.1620/tjem.206.253 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | vauthors=Boocock GR, Marit MR, Rommens JM |title=Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. |journal=Genomics |volume=87 |issue= 6 |pages= 758–71 |year= 2006 |pmid= 16529906 |doi= 10.1016/j.ygeno.2006.01.010 }}
*{{cite journal | author=Andersen JS, Lam YW, Leung AK, ''et al.'' |title=Nucleolar proteome dynamics. |journal=Nature |volume=433 |issue= 7021 |pages= 77-83 |year= 2005 |pmid= 15635413 |doi= 10.1038/nature03207 }}
*{{cite journal   |vauthors=Erdos M, Alapi K, Balogh I, etal |title=Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene. |journal=Exp. Hematol. |volume=34 |issue= 11 |pages= 1517–21 |year= 2007 |pmid= 17046571 |doi= 10.1016/j.exphem.2006.06.009 }}
*{{cite journal | author=Kuijpers TW, Alders M, Tool AT, ''et al.'' |title=Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship. |journal=Blood |volume=106 |issue= 1 |pages= 356-61 |year= 2005 |pmid= 15769891 |doi= 10.1182/blood-2004-11-4371 }}
*{{cite journal   |vauthors=Nishimura G, Nakashima E, Hirose Y, etal |title=The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type. |journal=J. Med. Genet. |volume=44 |issue= 4 |pages= e73 |year= 2007 |pmid= 17400792 |doi= 10.1136/jmg.2006.043869 | pmc=2598034 }}
*{{cite journal  | author=Austin KM, Leary RJ, Shimamura A |title=The Shwachman-Diamond SBDS protein localizes to the nucleolus. |journal=Blood |volume=106 |issue= 4 |pages= 1253-8 |year= 2005 |pmid= 15860664 |doi= 10.1182/blood-2005-02-0807 }}
*{{cite journal   |vauthors=Calado RT, Graf SA, Wilkerson KL, etal |title=Mutations in the SBDS gene in acquired aplastic anemia. |journal=Blood |volume=110 |issue= 4 |pages= 1141–6 |year= 2007 |pmid= 17478638 |doi= 10.1182/blood-2007-03-080044 | pmc=1939897 }}
*{{cite journal | author=Kawakami T, Mitsui T, Kanai M, ''et al.'' |title=Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations. |journal=Tohoku J. Exp. Med. |volume=206 |issue= 3 |pages= 253-9 |year= 2005 |pmid= 15942154 |doi=  }}
*{{cite journal   |vauthors=Wang Y, Yagasaki H, Hama A, etal |title=Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children. |journal=Haematologica |volume=92 |issue= 11 |pages= 1573 |year= 2007 |pmid= 18024409 |doi= 10.3324/haematol.11568 }}
*{{cite journal  | author=Boocock GR, Marit MR, Rommens JM |title=Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. |journal=Genomics |volume=87 |issue= 6 |pages= 758-71 |year= 2006 |pmid= 16529906 |doi= 10.1016/j.ygeno.2006.01.010 }}
*{{cite journal | author=Erdos M, Alapi K, Balogh I, ''et al.'' |title=Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene. |journal=Exp. Hematol. |volume=34 |issue= 11 |pages= 1517-21 |year= 2007 |pmid= 17046571 |doi= 10.1016/j.exphem.2006.06.009 }}
*{{cite journal | author=Nishimura G, Nakashima E, Hirose Y, ''et al.'' |title=The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type. |journal=J. Med. Genet. |volume=44 |issue= 4 |pages= e73 |year= 2007 |pmid= 17400792 |doi= 10.1136/jmg.2006.043869 }}
*{{cite journal | author=Calado RT, Graf SA, Wilkerson KL, ''et al.'' |title=Mutations in the SBDS gene in acquired aplastic anemia. |journal=Blood |volume=110 |issue= 4 |pages= 1141-6 |year= 2007 |pmid= 17478638 |doi= 10.1182/blood-2007-03-080044 }}
*{{cite journal | author=Wang Y, Yagasaki H, Hama A, ''et al.'' |title=Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children. |journal=Haematologica |volume=92 |issue= 11 |pages= 1573 |year= 2007 |pmid= 18024409 |doi= 10.3324/haematol.11568 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
==External links==
{{WikiDoc Sources}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sds GeneReviews/NIH/NCBI/UW entry on Shwachman-Diamond Syndrome]
 
{{InterPro content|IPR002140}}

Latest revision as of 05:56, 11 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Ribosome maturation protein SBDS is a protein that in humans is encoded by the SBDS gene.[1] 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.[2] 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.[2] The precise function of the SBDS protein is not known but it appears to play an important role in ribosome function or assembly.[3] 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.[4]

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.[1][5]

A number of uncharacterised hydrophilic proteins of about 30 kDa share regions of similarity. These include,

This particular protein sequence is highly conserved in species ranging from archaea to vertebrates and plants.[1]

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.[3]

SBDS N-terminal domain

SBDS protein N-terminal domain
Identifiers
SymbolSBDS
PfamPF01172
InterProIPR019783
PROSITEPDOC00974
SCOP1nyn
SUPERFAMILY1nyn

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.[5]

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.[5]

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.[5]

Structure

This domain contains a very common structure, the winged helix-turn-helix.[5]

SBDS C-terminal domain

SBDS protein C-terminal domain
Identifiers
SymbolSBDS_C
PfamPF09377
InterProIPR018978
SCOP1nyn
SUPERFAMILY1nyn

In molecular biology, the SBDS C-terminal protein domain is highly conserved in species ranging from archaea to vertebrates and plants.[6]

Function

Members of this family are thought to play a role in RNA metabolism.[5] However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.[5]

Structure

The structure of the C-terminal domain contains a ferredoxin-like fold[7] This structure has a four-stranded beta-sheet with two helices on one side.[5]

Clinical significance

Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome .[2] 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).[3]

References

  1. ↑ 1.0 1.1 1.2 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.
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome".
  3. ↑ 3.0 3.1 3.2 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.
  4. ↑ 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.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 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.
  6. ↑ 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.
  7. ↑ 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

External links

This article incorporates text from the public domain Pfam and InterPro: IPR002140
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