Jump to content

SBDS

From Wikipedia, the free encyclopedia
(Redirected from SBDS (gene))

SBDS
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSBDS, SDS, SWDS, CGI-97, SBDS ribosome assembly guanine nucleotide exchange factor, ribosome maturation factor, SBDS ribosome maturation factor, SDO1
External IDsOMIM: 607444; MGI: 1913961; HomoloGene: 6438; GeneCards: SBDS; OMA:SBDS - orthologs
Orthologs
SpeciesHumanMouse
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: 66.99 – 67 MbChr 5: 130.27 – 130.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ribosome maturation protein SBDS is a protein that in humans is encoded by the SBDS gene.[5] 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.[6] This gene encodes a member of a highly conserved protein family that exists in all archaea and eukaryotes.

Function

[edit]

The encoded protein plays an essential role in ribosome biogenesis. SBDS interacts with elongation factor-like GTPase 1 (Efl1) to disassociate eukaryotic initiation factor 6 (eIF6) from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S.[6] Dynamic rotation of the SBDS protein in the ribosomal P site is coupled to a conformational switch in EFL1 that promotes eIF6 displacement through competition for an overlapping binding site on the 60S ribosomal subunit.[7] Yeast SBDS ortholog, Sdo1, functions within a pathway containing Efl1 to facilitate the release and recycling of the nucleolar shuttling factor Tif6 (yeast eIF6 ortholog) from late cytoplasmic pre-60S ribosomal subunit.[8] Knockdown of SBDS expression results in increased apoptosis in erythroid cells undergoing differentiation due to elevated ROS levels.[9] Hence SBDS is critical for normal erythropoiesis.[10]

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.[5][11]

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.[5]

Structure

[edit]

The SBDS protein contains three domains, an N-terminal conserved FYSH domain, central helical domain and C-terminal domain containing an RNA-binding motif.[9]

N-terminal domain

[edit]
SBDS protein N-terminal domain
Identifiers
SymbolSBDS
PfamPF01172
InterProIPR019783
PROSITEPDOC00974
SCOP21nyn / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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.[11]

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.[11]

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.[11]

This domain contains a very common structure, the winged helix-turn-helix.[11]

C-terminal domain

[edit]
SBDS protein C-terminal domain
Identifiers
SymbolSBDS_C
PfamPF09377
InterProIPR018978
SCOP21nyn / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

In molecular biology, the SBDS C-terminal protein domain is highly conserved in species ranging from archaea to vertebrates and plants.[5]

Members of this family are thought to play a role in RNA metabolism.[11] However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.[11]

The structure of the C-terminal domain contains a ferredoxin-like fold[12] This structure has a four-stranded beta-sheet with two helices on one side.[11]

Clinical significance

[edit]

Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome.[6] 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).[9]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126524 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025337 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d 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". Nature Genetics. 33 (1): 97–101. doi:10.1038/ng1062. PMID 12496757. S2CID 5091627.
  6. ^ a b c "Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome".
  7. ^ Weis F, Giudice E, Churcher M, Jin L, Hilcenko C, Wong CC, et al. (November 2015). "Mechanism of eIF6 release from the nascent 60S ribosomal subunit". Nature Structural & Molecular Biology. 22 (11): 914–9. doi:10.1038/nsmb.3112. PMC 4871238. PMID 26479198.
  8. ^ Menne TF, Goyenechea B, Sánchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, et al. (April 2007). "The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast". Nature Genetics. 39 (4): 486–95. doi:10.1038/ng1994. PMID 17353896. S2CID 8076230.
  9. ^ 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. Bibcode:2011PLoSO...620727O. doi:10.1371/journal.pone.0020727. PMC 3113850. PMID 21695142.
  10. ^ Sen S, Wang H, Nghiem CL, Zhou K, Yau J, Tailor CS, et al. (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. S2CID 16823156.
  11. ^ a b c d e f g h Savchenko A, Krogan N, Cort JR, Evdokimova E, Lew JM, Yee AA, et al. (May 2005). "The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism". The Journal of Biological Chemistry. 280 (19): 19213–20. doi:10.1074/jbc.M414421200. PMID 15701634.
  12. ^ Shammas C, Menne TF, Hilcenko C, Michell SR, Goyenechea B, Boocock GR, et al. (May 2005). "Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome". The Journal of Biological Chemistry. 280 (19): 19221–9. doi:10.1074/jbc.M414656200. PMID 15701631.

Further reading

[edit]
[edit]
This article incorporates text from the public domain Pfam and InterPro: IPR002140
Retrieved from "https://en.wikipedia.org/w/index.php?title=SBDS&oldid=1213775975"