From Wikipedia, the free encyclopedia
Jump to: navigation, search
Shwachman-Bodian-Diamond syndrome
Crystallographic structure of the human Shwachman-Bodian-Diamond syndrome (SBDS) protein (rainbow colored, N-terminus = blue, C-terminus = red).[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols SBDS ; SDS; SWDS
External IDs OMIM607444 MGI1913961 HomoloGene6438 GeneCards: SBDS Gene
Species Human Mouse
Entrez 51119 66711
Ensembl ENSG00000126524 ENSMUSG00000025337
UniProt Q9Y3A5 P70122
RefSeq (mRNA) NM_016038 NM_023248
RefSeq (protein) NP_057122 NP_075737
Location (UCSC) Chr 7:
66.45 – 66.46 Mb
Chr 5:
130.25 – 130.26 Mb
PubMed search [1] [2]

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.


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,

This particular protein sequence is highly conserved in species ranging from archaea to vertebrates and plants.[2]


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[edit]

SBDS protein N-terminal domain
Symbol SBDS
Pfam PF01172
InterPro IPR019783
SCOP 1nyn


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]


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[edit]


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]


This domain contains a very common structure, the winged helix-turn-helix.[6]

SBDS C-terminal domain[edit]

SBDS protein C-terminal domain
Symbol SBDS_C
Pfam PF09377
InterPro IPR018978
SCOP 1nyn

In molecular biology, the SBDS C-terminal protein domain is highly conserved in species ranging from archaea to vertebrates and plants.[7]


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]


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[edit]

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]


  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b c "Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome". 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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[edit]

External links[edit]

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