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7  structures 473  species 1  interaction 652  sequences 6  architectures

Family: SBDS (PF01172)

Summary: Shwachman-Bodian-Diamond syndrome (SBDS) protein

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SBDS Edit Wikipedia article

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
Identifiers
Symbols SBDS; SDS; SWDS
External IDs OMIM607444 MGI1913961 HomoloGene6438 GeneCards: SBDS Gene
Orthologs
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.

Function[edit]

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]

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.[4]

SBDS N-terminal domain[edit]

SBDS protein N-terminal domain
Identifiers
Symbol SBDS
Pfam PF01172
InterPro IPR019783
PROSITE PDOC00974
SCOP 1nyn
SUPERFAMILY 1nyn

Function[edit]

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[edit]

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]

Function[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]

Structure[edit]

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

SBDS C-terminal domain[edit]

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

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

Function[edit]

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[edit]

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]

References[edit]

  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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Shwachman-Bodian-Diamond syndrome (SBDS) protein 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. It is characterised by bone marrow failure and leukemia predisposition. Members of this family play a role in RNA metabolism [2] [3]. In yeast these proteins have been shown to be critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes [4]. This data links defective late 60S subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition [4].

Literature references

  1. 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

  2. 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

  3. 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

  4. Menne TF, Goyenechea B, Sanchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, Brost RL, Costanzo M, Boone C, Warren AJ; , Nat Genet. 2007;39:486-495.: The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. PUBMED:17353896 EPMC:17353896


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019783

This entry represents the N-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,

Domain organisation

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Alignments

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(103)
Full
(652)
Representative proteomes NCBI
(614)
Meta
(94)
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(143)
RP35
(255)
RP55
(370)
RP75
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  Seed
(103)
Full
(652)
Representative proteomes NCBI
(614)
Meta
(94)
RP15
(143)
RP35
(255)
RP55
(370)
RP75
(444)
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  Seed
(103)
Full
(652)
Representative proteomes NCBI
(614)
Meta
(94)
RP15
(143)
RP35
(255)
RP55
(370)
RP75
(444)
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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.

Pfam alignments:

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Curation and family details

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Curation View help on the curation process

Seed source: Prosite
Previous IDs: UPF0023;
Type: Family
Author: Finn RD, Bateman A, Moxon SJ, Mistry J, Wood V
Number in seed: 103
Number in full: 652
Average length of the domain: 91.60 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 38.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.4 24.4
Trusted cut-off 25.5 27.0
Noise cut-off 20.0 24.3
Model length: 91
Family (HMM) version: 13
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Species distribution

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Interactions

There is 1 interaction for this family. More...

SBDS_C

Structures

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 domain has been found. There are 7 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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