Affinage

SBDS

Ribosome maturation protein SBDS · UniProt Q9Y3A5

Length
250 aa
Mass
28.8 kDa
Annotated
2026-06-10
71 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SBDS is a cytoplasmic ribosome maturation factor that licenses the final step of 60S large subunit assembly, cooperating with the GTPase EFL1 to evict the anti-association factor eIF6 and enable 80S monosome formation (PMID:22997148, PMID:28331068). Structurally it is a conserved three-domain protein—an N-terminal FYSH (domain I) RNA-binding fold, a central three-helical bundle (domain II) that confers species specificity, and a C-terminal ferredoxin-like domain (domain III)—with the FYSH domain concentrating most Shwachman-Diamond syndrome (SDS) mutations (PMID:15701631, PMID:16529906, PMID:20053358). On the mature 60S subunit it binds at the P-site, contacting H69, H38, uL16 and uL5 through domains I and II, positioning it to relay a conformational signal through uL16 and EFL1 that controls eIF6 departure; it engages EFL1 directly via the GTPase's disordered insertion domain and SBDS domains II–III (PMID:24406167, PMID:26850260, PMID:28331068). SBDS localizes to the nucleolus in an active-rRNA-transcription-dependent, cell-cycle-regulated manner and co-migrates with 60S subunits, and its loss causes nuclear retention of pre-60S subunits, impaired eIF6 recycling, and reduced 80S/global translation (PMID:15860664, PMID:17475909, PMID:22997148, PMID:28056084). Loss of SBDS function drives p53 activation through the RPL5/RPL11–MDM2 ribosomal stress pathway, producing cell-type-specific outcomes—apoptosis in hematopoietic, embryonic and neuronal cells versus senescence in pancreatic acinar cells—which underlies the tissue pathology of Shwachman-Diamond syndrome, in which SBDS is mutated (PMID:12496757, PMID:26185170, PMID:26057580, PMID:32198344, PMID:32759502). Beyond ribosome biogenesis, SBDS binds microtubules and the MTOC and is subject to M-phase RNF2-mediated ubiquitination and degradation that accelerates mitotic progression (PMID:19759903, PMID:35158210, PMID:37806249), supports translation re-initiation at C/EBPα/β uORFs to control myeloid proliferation (PMID:26762974), and facilitates telomerase recruitment to telomeres via direct binding to TPP1 (PMID:29444436).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 2002 Low

    Established the first functional hypothesis by placing SBDS in a conserved protein family whose archaeal members sit in RNA-processing operons, framing it as an RNA-metabolism factor.

    Evidence Genomic/sequence analysis and disease-gene sequencing

    PMID:12496757

    Open questions at the time
    • Computational inference only, no biochemical activity demonstrated
    • No specific RNA substrate or ribosomal role tested
  2. 2005 High

    Resolved the protein architecture and which regions matter, showing the FYSH domain and central helical bundle are essential while the common K62X truncation is non-functional, linking structure to disease mutations.

    Evidence 1.9 Å crystal structure of the A. fulgidus ortholog plus yeast complementation and mutagenesis

    PMID:15701631

    Open questions at the time
    • Archaeal ortholog structure, not human
    • No bound ligand or ribosome to define functional surfaces
  3. 2005 Medium

    Defined the subcellular setting by showing cell-cycle-dependent nucleolar localization, pointing to a role coupled to ribosome biogenesis.

    Evidence Immunofluorescence with cell-cycle staging in patient fibroblasts and controls

    PMID:15860664

    Open questions at the time
    • Localization alone does not establish molecular function
    • Trafficking determinants not identified
  4. 2006 High

    Demonstrated SBDS is essential for early mammalian development, consistent with the absence of homozygous null patients.

    Evidence Constitutive Sbds knockout mouse with embryonic-lethal phenotype

    PMID:16914746

    Open questions at the time
    • Does not pinpoint the lethal molecular defect
    • Cell-autonomous mechanism in epiblast not resolved
  5. 2006 Medium

    Mapped functional domain conservation, showing the FYSH domain is interchangeable across eukaryotes while domain II confers species specificity and domain III is largely dispensable in yeast.

    Evidence Yeast complementation with interspecies chimeras and truncations

    PMID:16529906

    Open questions at the time
    • Mechanistic basis of species specificity unexplained
    • Domain III function not defined despite dispensability in yeast
  6. 2007 High

    Connected SBDS physically to the large ribosomal subunit, showing co-migration with 60S, 28S rRNA association, nucleophosmin complex formation, and transcription-dependent nucleolar enrichment.

    Evidence Sucrose-gradient sedimentation, RNA co-precipitation, co-IP, actinomycin D sensitivity with complementation

    PMID:17475909

    Open questions at the time
    • Did not define SBDS's catalytic or maturation step on the 60S
    • eIF6/EFL1 axis not yet implicated
  7. 2007 High

    Linked SBDS loss to the hematopoietic phenotypes of SDS, showing defective granulocytic differentiation, impaired progenitor output, and reduced bone-marrow homing.

    Evidence Lentiviral shRNA knockdown with in vitro differentiation and in vivo transplantation/homing assays

    PMID:17638857

    Open questions at the time
    • Molecular link between ribosome defect and differentiation block unresolved
    • Homing mechanism not defined
  8. 2008 Medium

    Identified the extrinsic Fas/caspase-8 pathway as the route to apoptosis in SBDS-deficient cells, placing SBDS upstream of Fas-mediated death.

    Evidence shRNA knockdown with Fas stimulation, caspase-8/9 inhibitor rescue, apoptosis-protein blotting in HeLa

    PMID:18268284

    Open questions at the time
    • Connection to ribosome/p53 stress not established here
    • Single cell line
  9. 2009 Medium

    Provided a mechanism for Fas hypersensitivity, showing surface Fas accumulation via increased Fas transcript 1 without altered total Fas or internalization, and stimulus specificity for Fas.

    Evidence shRNA knockdown, surface-Fas flow cytometry, RT-PCR, apoptosis assays with multiple stimuli

    PMID:19009351

    Open questions at the time
    • How SBDS loss alters Fas transcript splicing/selection unknown
    • Relationship to ribosomal stress not tested
  10. 2009 Medium

    Revealed a non-ribosomal activity by showing direct microtubule and MTOC association in myeloid progenitors.

    Evidence Immunofluorescence co-localization and in vitro microtubule-binding assay

    PMID:19759903

    Open questions at the time
    • Functional consequence of microtubule binding not established here
    • Binding interface on SBDS not mapped
  11. 2010 Medium

    Implicated oxidative stress as a driver, showing elevated ROS underlies spontaneous and Fas-mediated apoptosis and that antioxidants rescue growth.

    Evidence shRNA knockdown in HeLa/TF-1, ROS and apoptosis assays with antioxidant rescue

    PMID:20979173

    Open questions at the time
    • Source of ROS in SBDS deficiency unidentified
    • Causal order between ROS, Fas, and ribosomal stress unclear
  12. 2010 High

    Extended SBDS function to skeletal biology, showing it is required for osteoclast migration and fusion via a Rac2-dependent pathway and RANK/DC-STAMP signaling.

    Evidence Conditional Sbds knockout monocytes, osteoclastogenesis assays, Rho-GTPase blotting, Rac2 rescue

    PMID:21084708

    Open questions at the time
    • How ribosome maturation defect selectively lowers Rac2 not resolved
    • Rac2 rescued migration but not osteoclastogenesis, implying additional defects
  13. 2010 High

    Delivered the human full-length structure and localized RNA binding to the FYSH domain, showing interdomain conformational exchange relevant to function.

    Evidence Solution NMR structure, dynamics, and RNA titration of human SBDS

    PMID:20053358

    Open questions at the time
    • RNA target on the ribosome not defined
    • Functional role of interdomain motion not directly tested
  14. 2012 Medium

    Identified the maturation step SBDS controls, showing knockdown causes nuclear retention of 60S subunits, reduced free 60S/80S, and increased eIF6 association—impaired eIF6 recycling.

    Evidence RNAi, RPL29-GFP localization, polysome profiling, eIF6 co-fractionation in TF-1/A549

    PMID:22997148

    Open questions at the time
    • Did not establish direct SBDS-EFL1 cooperation
    • Modest (~20%) eIF6 change leaves quantitative role open
  15. 2012 High

    Tied the ribosome defect to organ pathology, showing pancreas-specific Sbds loss recapitulates SDS exocrine disease with defective 80S formation.

    Evidence Pancreas-specific conditional knockout, ribosomal complex analysis, enzyme assays

    PMID:22510201

    Open questions at the time
    • Downstream signaling to acinar loss not resolved here
    • Why pancreas is selectively vulnerable unexplained
  16. 2014 High

    Reconstituted the direct SBDS-EFL1 interaction in vitro, mapping it to EFL1's disordered insertion domain and SBDS domains II-III, with insertion-domain folding upon binding.

    Evidence SEC, gel shift, ITC, CD, and domain-truncation mutagenesis

    PMID:24406167

    Open questions at the time
    • Interaction stoichiometry on the ribosome not shown
    • Functional GTPase consequence tested separately
  17. 2016 High

    Defined the structural basis of surveillance, showing the ortholog binds the 60S P-site near uL16/uL5 contacting H69/H38, supporting a uL16-Sdo1p-Efl1p relay that triggers eIF6 release.

    Evidence Cryo-EM of 60S-Sdo1p complexes with biochemical interaction assays

    PMID:26850260

    Open questions at the time
    • Conformational relay inferred from static structure
    • 2:2 60S dimer's physiological relevance unclear
  18. 2016 High

    Revealed a specialized translational role, showing SBDS is required for uORF re-initiation in C/EBPα/β mRNAs, controlling myeloid isoform output, MYC, and proliferation.

    Evidence Knockdown/mutation in myeloid cells, isoform Western blots, uORF luciferase reporters, proliferation assays

    PMID:26762974

    Open questions at the time
    • Mechanistic link between 60S maturation and re-initiation specificity not fully resolved
    • Breadth of uORF targets beyond C/EBP not defined
  19. 2017 High

    Molecularly cemented the SBDS-EFL1-eIF6 axis, showing SDS-like EFL1 mutants retain GTPase activity and SBDS activation but fail to evict eIF6, demonstrating cooperative function.

    Evidence GTPase assay, yeast complementation, Tif6-GFP localization, CD, SAXS

    PMID:28331068

    Open questions at the time
    • Exact conformational coupling between GTP hydrolysis and eIF6 release not visualized
    • Human in vivo confirmation indirect
  20. 2017 High

    Provided a system-level view of SBDS deficiency, showing immature 60S accumulation, reduced translation, metabolic rewiring toward catabolism, and DNA-damage susceptibility, all rescued by wild-type Sbds.

    Evidence Knockin MEF immortalization with reconstitution, polysome/RNA-seq/translational/metabolic/DNA-damage profiling

    PMID:28056084

    Open questions at the time
    • Causal chain from translation deficit to metabolic shift not dissected
    • DNA-damage link mechanism unresolved
  21. 2015 High

    Defined the cell-type-specific stress response, showing Sbds loss triggers p53-dependent apoptosis in hematopoietic/embryonic/neuronal tissue but TGFβ-driven senescence in pancreatic acinar cells, with p53 ablation differentially rescuing.

    Evidence Tissue-specific and constitutive Sbds knockouts, p53 epistasis, IHC, expression analysis (and Cebpa-targeted myeloid model)

    PMID:26057580 PMID:26185170

    Open questions at the time
    • What dictates apoptosis-versus-senescence choice per tissue not fully defined
    • Upstream sensor coupling ribosome defect to p53 in each tissue varies
  22. 2018 Medium

    Uncovered a telomere-maintenance role, showing SBDS binds TPP1 during S phase to facilitate telomerase recruitment without altering TERT catalytic activity.

    Evidence Co-IP (SBDS-TPP1), telomerase ChIP, telomere-length and TERT activity assays, cell-cycle staging

    PMID:29444436

    Open questions at the time
    • Direct SBDS-TPP1 binding interface not mapped
    • Relationship to ribosomal function of SBDS unclear
  23. 2020 Medium

    Defined dual p53-regulatory mechanisms, showing SBDS knockdown activates p53 via RPL5/RPL11-MDM2 stress and nucleoplasmic SBDS can directly bind p53 to block MDM2-mediated ubiquitination.

    Evidence Knockdown/overexpression, co-IP (SBDS-p53, MDM2-p53), ubiquitination/reporter assays, tumor assays

    PMID:32198344

    Open questions at the time
    • Physiological relevance of direct SBDS-p53 binding versus ribosomal stress unclear
    • Single lab, ectopic overexpression context
  24. 2020 High

    Showed p53-independent essential functions, with zebrafish sbds loss causing reduced 80S, neutropenia, and multi-organ atrophy that Tp53 deletion does not rescue from lethality.

    Evidence CRISPR sbds knockout zebrafish, polysome and transcriptome analysis, tp53 epistasis

    PMID:32759502

    Open questions at the time
    • Identity of the p53-independent lethal pathway unknown
    • Translation deficit-to-organ phenotype link not mechanistic
  25. 2022 Medium

    Identified RNF2 as an E3 ligase for SBDS, demonstrating direct interaction and RNF2-driven ubiquitination and proteasomal degradation.

    Evidence Yeast two-hybrid, GST pulldown with recombinant proteins, co-IP, ubiquitination assay

    PMID:35158210

    Open questions at the time
    • Cellular trigger and timing of degradation not addressed here
    • Ubiquitination sites on SBDS not mapped
  26. 2023 Medium

    Placed RNF2-mediated SBDS turnover in mitosis, showing M-phase co-localization on centrosomal microtubules where RNF2 degrades microtubule-bound SBDS to accelerate mitotic progression.

    Evidence Immunofluorescence co-localization, microtubule-binding assay, co-IP, ubiquitination assay, mitotic-progression analysis

    PMID:37806249

    Open questions at the time
    • How SBDS levels regulate mitotic timing mechanistically unclear
    • Link between mitotic and ribosomal pools of SBDS unresolved
  27. 2023 Low

    Suggested an additional binding partner, with FCN3 binding SBDS to modulate eIF6 nuclear translocation and trigger ribosomal-stress p53 activation in hepatocellular carcinoma.

    Evidence Co-IP (FCN3-SBDS), eIF6 localization, p53 reporter, proliferation assays

    PMID:36632465

    Open questions at the time
    • Single Co-IP without reciprocal/structural validation
    • Direct versus indirect FCN3-SBDS interaction unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ribosome-maturation factor coordinates its parallel roles in microtubule/mitotic regulation, telomere maintenance, uORF re-initiation, and tissue-specific p53 outcomes remains unresolved.
  • No unified model linking ribosomal and non-ribosomal SBDS pools
  • Mechanism dictating apoptosis-versus-senescence per tissue undefined
  • Structural basis of TPP1 and microtubule binding not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 2 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2 GO:0045182 translation regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005840 ribosome 3 GO:0005730 nucleolus 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1640170 Cell Cycle 1
Partners
EFL1EIF6FCN3NPM1RNF2TP53TPP1
Complex memberships
60S pre-ribosomal subunit

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SBDS is a member of a highly conserved protein family with putative orthologs in archaea and eukaryotes; archaeal orthologs reside within conserved operons that include homologs of RNA-processing genes, suggesting a role in RNA metabolism. Genomic/sequence analysis, identification of disease-associated mutations by gene sequencing Nature genetics Low 12496757
2005 The crystal structure of the Archaeoglobus fulgidus SBDS ortholog was solved at 1.9 Å resolution, revealing a three-domain architecture: an N-terminal FYSH domain (novel mixed α/β-fold), a central three-helical bundle, and a C-terminal ferredoxin-like fold. Genetic complementation in S. cerevisiae showed the FYSH domain and central three-helical bundle are essential, the common K62X truncation is non-functional, and missense mutations affecting buried hydrophobic core residues of the FYSH domain impair or abolish function. X-ray crystallography (1.9 Å), genetic complementation of yeast SBDS ortholog YLR022C, site-directed mutagenesis The Journal of biological chemistry High 15701631
2005 SBDS protein localizes to the nucleolus in a cell-cycle-dependent manner: nucleolar during G1 and G2 phases, and diffuse nuclear during S phase. Immunofluorescence/immunohistochemistry in patient fibroblasts and controls; cell-cycle staging Blood Medium 15860664
2006 Complementation studies across species showed that the FYSH (N-terminal) domain is widely interchangeable among eukaryotes while domain 2 (central three-helical bundle) imparts species specificity to SBDS function; domain 3 (C-terminal) is largely dispensable for function in the yeast complementation assay. Yeast (S. cerevisiae) complementation assay with interspecies chimeras and domain-truncated constructs Genomics Medium 16529906
2006 Homozygous deletion of murine Sbds causes embryonic lethality prior to E6.5 with failure of epiblast formation, demonstrating that Sbds is an essential gene for early mammalian development; heterozygous mice are phenotypically normal. Targeted gene disruption (knockout mouse), embryonic lethal phenotype analysis Molecular and cellular biology High 16914746
2007 Human SBDS is enriched in the nucleolus in an active rRNA transcription-dependent manner; SBDS co-migrates with the 60S large ribosomal subunit on sucrose gradients and co-precipitates with 28S rRNA; SBDS forms a protein complex with nucleophosmin; SDS patient cells and Diamond-Blackfan anemia cells are hypersensitive to actinomycin D, and wild-type SBDS expression complements this hypersensitivity. Sucrose gradient sedimentation, RNA co-precipitation, co-immunoprecipitation with nucleophosmin, actinomycin D sensitivity assay with complementation Blood High 17475909
2007 Lentiviral RNAi-mediated knockdown of Sbds in murine hematopoietic progenitors causes a defect in granulocytic differentiation in vitro, impairs myeloid progenitor generation in vivo, reduces homing of hematopoietic progenitors to bone marrow, and decreases circulating B lymphocytes. Lentiviral shRNA knockdown, in vitro differentiation assays, in vivo bone marrow transplantation and homing assay Blood High 17638857
2008 SBDS knockdown in HeLa cells leads to accelerated apoptosis via hypersensitivity to Fas stimulation; inhibition of Fas and caspase-8 (but not caspase-9) significantly improved defective cell growth, indicating SBDS acts upstream of the extrinsic (Fas/caspase-8) apoptosis pathway. BAX/BCL2/BCL-XL ratios were not elevated in knockdown cells. shRNA knockdown, Fas stimulation assay, caspase inhibitor rescue experiments, Western blotting of apoptosis pathway proteins, oligonucleotide microarray Haematologica Medium 18268284
2009 SBDS-deficient cells accumulate Fas at the plasma membrane (via increased Fas transcript 1 expression) without changes in total Fas protein/mRNA levels or Fas internalization, providing a mechanism for the specific Fas hypersensitivity; hypersensitivity was not observed with TNF-α, DNA-damaging agents, transcription inhibition, or protein synthesis inhibition. shRNA knockdown, flow cytometry for cell-surface Fas, Western blotting, RT-PCR for Fas transcripts, apoptosis assays with multiple stimuli Apoptosis Medium 19009351
2009 SBDS co-localizes with the mitotic spindle and microtubule organizing center (MTOC) in human myeloid progenitors, and in vitro binding studies reveal a direct interaction of SBDS with microtubules. Immunofluorescence microscopy, in vitro microtubule binding assay PloS one Medium 19759903
2010 SBDS deficiency results in increased intracellular reactive oxygen species (ROS), which drives both spontaneous and Fas-mediated apoptosis and reduced cell growth; antioxidant treatment rescues SBDS-deficient cells from apoptosis and restores cell growth. shRNA knockdown in HeLa and TF-1 cells, ROS assay (DCFH-DA), annexin V/PI apoptosis assay, MTT cell growth assay with antioxidant rescue Pediatric blood & cancer Medium 20979173
2010 Sbds is required for osteoclastogenesis: Sbds-null murine monocytes form fewer and smaller osteoclasts due to impaired migration and fusion. Sbds deficiency causes a 5-fold decrease in Rac2 (but not Rac1, Cdc42, or RhoA), and Rac2 supplementation rescues migration but not osteoclastogenesis. Impaired signaling downstream of RANK and reduced expression of DC-STAMP also contribute to defective osteoclast differentiation. Sbds conditional knockout mouse, in vitro osteoclastogenesis assay, Western blotting of Rho GTPases, Rac2 supplementation rescue, DC-STAMP expression analysis Blood High 21084708
2010 Solution NMR structure of full-length human SBDS was determined, revealing three well-folded domains with significant conformational exchange between the N-terminal and central domains. RNA-binding activity was mapped to the N-terminal FYSH domain, which concentrates most SDS-associated mutations. NMR spectroscopy (solution structure and backbone dynamics), NMR RNA titration and chemical shift mapping Journal of molecular biology High 20053358
2011 Patient-related truncated SBDS protein isoforms localize predominantly to the nucleus (loss of cytoplasmic localization), and their nucleo-cytoplasmic trafficking is disturbed. A sumoylation motif in the C-terminal domain plays a pivotal role in intracellular mobility; this motif is absent in truncated patient SBDS proteins. Live cell imaging, FRAP, mutant SBDS transfection series, identification of sumoylation motif by mutagenesis PloS one Medium 21695142
2012 Disruption of Sbds specifically in the murine pancreas recapitulates SDS pancreatic phenotypes including decreased pancreatic mass, fat infiltration, hypoplastic exocrine compartment, loss of zymogen granules, defects in 80S ribosomal complex formation, reduced serum digestive enzymes, and overall growth impairment. Pancreas-specific conditional knockout (Cre-lox), ribosomal complex analysis, enzyme assays Gastroenterology High 22510201
2012 Knockdown of SBDS in human cells (TF-1 and A549) leads to nuclear retention of 60S ribosomal subunits (assessed by RPL29-GFP), decreased free 60S and 80S subunits in polysome profiles, and approximately 20% increased eIF6 association with the 60S subunit, indicating impaired eIF6 recycling and nuclear export of pre-60S subunits. RNAi knockdown, RPL29-GFP localization assay, polysome gradient analysis, eIF6 co-fractionation Pediatric blood & cancer Medium 22997148
2014 EFL1 interacts directly with SBDS, with the interaction mediated by the intrinsically disordered insertion domain of EFL1 and domains II–III of SBDS, as determined by size exclusion chromatography, gel shift assay, and isothermal titration calorimetry. The insertion domain of EFL1 acquires a fixed conformation upon complex formation with SBDS. Size exclusion chromatography, gel shift assay, isothermal titration calorimetry (ITC), circular dichroism spectroscopy, domain-truncation mutagenesis Biochemical and biophysical research communications High 24406167
2015 Sbds deficiency in the myeloid lineage (targeted to Cebpa-expressing hematopoietic stem and progenitor cells) causes neutropenia by selectively impairing myelocyte differentiation and inducing p53 pathway activation and apoptosis specifically in myelocytes and downstream progeny, while rapidly cycling progenitors are unaffected. Conditional Cebpa-Cre Sbds knockdown mouse model, flow cytometry, massive parallel sequencing, apoptosis assays Haematologica High 26185170
2015 Targeted disruption of Sbds in murine pancreatic acinar cells causes early p53 stabilization and senescence (via Tgfβ, p15Ink4b, and senescence-associated secretory program) rather than apoptosis; genetic ablation of p53 resolves acinar hypoplasia and enzyme synthesis defects but leads to dedifferentiation and extensive apoptosis. In embryonic tissues and neurons, Sbds ablation causes p53-dependent apoptosis. Tgfβ signature is pancreas-specific and not detected in fetal bone marrow, liver, or brain. Pancreas-specific and constitutive Sbds knockout mice, p53 double-knockout epistasis, immunohistochemistry, gene expression analysis PLoS genetics High 26057580
2016 SBDS protein is specifically required for translation re-initiation at upstream open reading frames (uORFs) in the 5'UTRs of C/EBPα and C/EBPβ mRNAs, leading to reduced production of the C/EBPα-p30 and C/EBPβ-LIP isoforms upon SBDS mutation or knockdown. This results in decreased MYC expression and reduced proliferation of myeloid progenitors. SBDS knockdown/mutation in myeloid cells, isoform-specific Western blotting, luciferase reporter assays for uORF-dependent translation re-initiation, proliferation assays Nucleic acids research High 26762974
2016 Yeast Sdo1p (SBDS ortholog) interacts tightly with the mature 60S ribosomal subunit through domains I and II, binds at the ribosomal P-site in proximity to uL16 and uL5 with direct contact to H69 and H38, and is capable of bridging two 60S subunits to form a stable 2:2 dimer. This strategic binding position supports a surveillance role in monitoring conformational maturation of the P-site and a conformational signal-relay cascade involving uL16, Sdo1p, and Efl1p controlling eIF6 departure. Cryo-EM structural analysis of 60S–Sdo1p complexes, in vitro biochemical interaction assays Protein & cell High 26850260
2017 Mutant EFL1 proteins (R1095Q, M882K) associated with an SDS-like syndrome do not affect GTPase activity or its activation by SBDS or the 60S subunit, but fail to promote release of cytoplasmic Tif6 (eIF6) from the 60S subunit, likely preventing mature 80S ribosome formation. This establishes that SBDS functions cooperatively with EFL1 to evict eIF6 from the 60S subunit. GTPase activity assay (malachite green), yeast complementation, Tif6-GFP localization by fluorescence microscopy, circular dichroism, SAXS Journal of medical genetics High 28331068
2017 SbdsR126T/R126T mouse embryonic fibroblasts show increased immature 60S subunits, reduced global protein synthesis, reduced clonogenic capacity, oncogene-induced transformation resistance, rewired gene expression with reduced ribosomal and increased lysosomal/catabolic activity, reduced ATP and lactate, and increased susceptibility to DNA damage. Reconstitution with wild-type Sbds rescues these phenotypes. Mouse embryonic fibroblast immortalization from knockin mice, reconstitution with WT Sbds, polysome profiling, RNA-seq, translational profiling, metabolic assays, DNA damage assays PLoS genetics High 28056084
2018 SBDS is required for telomere maintenance by facilitating telomerase recruitment to telomeres; SBDS directly binds TPP1 during S phase, stabilizing the TPP1–telomerase interaction. Overexpression of disease-associated SBDS mutants or SBDS knockdown impairs telomerase recruitment to telomeres without affecting overall telomerase reverse transcriptase activity. Co-immunoprecipitation (SBDS-TPP1), ChIP for telomerase at telomeres, telomere length assay, TERT activity assay, cell-cycle staging Cell reports Medium 29444436
2020 SBDS knockdown leads to p53 stabilization and activation via the ribosomal stress RPL5/RPL11–MDM2 pathway, repressing cancer cell proliferation. Additionally, ectopically expressed SBDS in the nucleoplasm binds to the transactivation domain of p53, perturbs MDM2–p53 interaction, and impairs p53 ubiquitination and proteasomal degradation, activating p53 by a second mechanism. SBDS knockdown and overexpression, co-immunoprecipitation (SBDS–p53, MDM2–p53), ubiquitination assay, p53 reporter and Western blotting, in vitro and in vivo tumor assays Cell death & disease Medium 32198344
2020 Loss of Sbds in zebrafish leads to decreased 80S ribosomes (polysome analysis), neutropenia by 5 dpf, and atrophy of pancreas, liver, and intestine. Tp53 pathway is activated (cdkn1a, ccng1, puma, mdm2 upregulation), but elimination of Tp53 function does not prevent lethality. CRISPR/Cas9 sbds knockout zebrafish, polysome analysis, transcriptome analysis, tp53 genetic epistasis JCI insight High 32759502
2022 SBDS interacts with Ring finger protein 2 (RNF2) as identified by yeast two-hybrid screening and confirmed by GST pulldown with recombinant proteins and co-immunoprecipitation in HEK293T cells. RNF2 ubiquitinates SBDS and promotes its proteasomal degradation. Yeast two-hybrid, GST pulldown with recombinant proteins, co-immunoprecipitation, ubiquitination assay Biochemical and biophysical research communications Medium 35158210
2023 SBDS co-localizes with RNF2 specifically on centrosomal microtubules during M phase (while in interphase SBDS is in the nucleolus and RNF2 in the nucleoplasm). SBDS interacts directly with microtubules (microtubule-binding assay), RNF2 interacts with SBDS bound to microtubules, and RNF2 ubiquitinates and degrades SBDS during M phase, thereby accelerating mitotic progression. Immunofluorescence co-localization, microtubule binding assay, co-immunoprecipitation, ubiquitination assay, RNF2 overexpression with mitotic progression analysis Biochemical and biophysical research communications Medium 37806249
2023 FCN3 binds SBDS and modulates nuclear translocation of eIF6, inducing ribosomal stress and p53 pathway activation, leading to apoptosis and inhibition of HCC cell proliferation. Co-immunoprecipitation (FCN3–SBDS), eIF6 localization assay, p53 pathway reporter, overexpression/knockdown proliferation assays International journal of biological sciences Low 36632465

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nature genetics 578 12496757
2009 Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. British journal of haematology 131 19775295
2007 The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood 115 17475909
2004 Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome. Blood 103 15284109
2017 Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in aShwachman-Diamond like syndrome. Journal of medical genetics 99 28331068
2005 The Shwachman-Diamond SBDS protein localizes to the nucleolus. Blood 99 15860664
2004 Skeletal phenotype in patients with Shwachman-Diamond syndrome and mutations in SBDS. Clinical genetics 98 14984468
2005 Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome. The Journal of biological chemistry 92 15701631
2012 Impaired expression of DICER, DROSHA, SBDS and some microRNAs in mesenchymal stromal cells from myelodysplastic syndrome patients. Haematologica 91 22371183
2006 Loss of the mouse ortholog of the shwachman-diamond syndrome gene (Sbds) results in early embryonic lethality. Molecular and cellular biology 87 16914746
2004 Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome. Human genetics 57 14749921
2009 The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome. Leukemia 51 19148133
2007 Mutations in the SBDS gene in acquired aplastic anemia. Blood 49 17478638
2015 Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes. Haematologica 47 26185170
2010 SBDS-deficiency results in deregulation of reactive oxygen species leading to increased cell death and decreased cell growth. Pediatric blood & cancer 46 20979173
2008 SBDS-deficient cells undergo accelerated apoptosis through the Fas-pathway. Haematologica 46 18268284
2007 Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Blood 42 17638857
2015 In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency. PLoS genetics 40 26057580
2012 Deficiency of Sbds in the mouse pancreas leads to features of Shwachman-Diamond syndrome, with loss of zymogen granules. Gastroenterology 40 22510201
2009 SBDS expression and localization at the mitotic spindle in human myeloid progenitors. PloS one 36 19759903
2010 Sbds is required for Rac2-mediated monocyte migration and signaling downstream of RANK during osteoclastogenesis. Blood 35 21084708
2016 Shwachman-Bodian-Diamond syndrome (SBDS) protein deficiency impairs translation re-initiation from C/EBPα and C/EBPβ mRNAs. Nucleic acids research 34 26762974
2017 SBDS-Deficient Cells Have an Altered Homeostatic Equilibrium due to Translational Inefficiency Which Explains their Reduced Fitness and Provides a Logical Framework for Intervention. PLoS genetics 33 28056084
2011 The ribosome-related protein, SBDS, is critical for normal erythropoiesis. Blood 30 21963601
2020 Dual regulation of p53 by the ribosome maturation factor SBDS. Cell death & disease 28 32198344
2006 Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. Genomics 28 16529906
2004 Congenital aplastic anemia caused by mutations in the SBDS gene: a rare presentation of Shwachman-Diamond syndrome. Pediatrics 28 15342903
2005 Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations. The Tohoku journal of experimental medicine 25 15942154
2023 FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway. International journal of biological sciences 23 36632465
2009 SBDS-deficiency results in specific hypersensitivity to Fas stimulation and accumulation of Fas at the plasma membrane. Apoptosis : an international journal on programmed cell death 23 19009351
2006 Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene. Experimental hematology 22 17046571
2010 Structure, dynamics, and RNA interaction analysis of the human SBDS protein. Journal of molecular biology 21 20053358
2008 Magnetic resonance imaging findings of the pancreas in patients with Shwachman-Diamond syndrome and mutations in the SBDS gene. The Journal of pediatrics 20 18280855
2005 Mutation analysis of SBDS in pediatric acute myeloblastic leukemia. Pediatric blood & cancer 20 16007594
2008 Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A. Blood cells, molecules & diseases 18 19014892
2020 Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy. JCI insight 17 32759502
2018 Shwachman-Diamond Syndrome Protein SBDS Maintains Human Telomeres by Regulating Telomerase Recruitment. Cell reports 17 29444436
2014 Direct interaction between EFL1 and SBDS is mediated by an intrinsically disordered insertion domain. Biochemical and biophysical research communications 17 24406167
2008 Some cases of common variable immunodeficiency may be due to a mutation in the SBDS gene of Shwachman-Diamond syndrome. Clinical and experimental immunology 17 18190602
2006 Compound heterozygous mutations of the SBDS gene in a patient with Shwachman-Diamond syndrome, type 1 diabetes mellitus and osteoporosis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 14 17106217
2012 Impaired growth, hematopoietic colony formation, and ribosome maturation in human cells depleted of Shwachman-Diamond syndrome protein SBDS. Pediatric blood & cancer 13 22997148
2004 SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome: no predisposition to malignant transformation? Cancer genetics and cytogenetics 13 15474150
2007 Identification of a novel AluSx-mediated deletion of exon 3 in the SBDS gene in a patient with Shwachman-Diamond syndrome. Blood cells, molecules & diseases 12 17376717
2016 Structural dynamics of the yeast Shwachman-Diamond syndrome protein (Sdo1) on the ribosome and its implication in the 60S subunit maturation. Protein & cell 10 26850260
2023 Counteracting the Common Shwachman-Diamond Syndrome-Causing SBDS c.258+2T>C Mutation by RNA Therapeutics and Base/Prime Editing. International journal of molecular sciences 9 36835434
2019 Cooperative energetic effects elicited by the yeast Shwachman-Diamond syndrome protein (Sdo1) and guanine nucleotides modulate the complex conformational landscape of the elongation factor-like 1 (Efl1) GTPase. Biophysical chemistry 8 30780079
2022 Inducible Sbds deletion impairs bone marrow niche capacity to engraft donor bone marrow after transplantation. Blood advances 7 34625796
2014 Structural variation and missense mutation in SBDS associated with Shwachman-Diamond syndrome. BMC medical genetics 7 24898207
2013 Improving the glycosyltransferase activity of Agrobacterium tumefaciens glycogen synthase by fusion of N-terminal starch binding domains (SBDs). Biochimie 7 23796574
2024 Tuning SBDs as Endoplasmic Reticulum Self-Targeting Fluorophores and Its Application for Zn2+ Tracking in ER Stress. Chemical & biomedical imaging 6 40443554
2022 A Comparative Molecular Dynamics Study of Selected Point Mutations in the Shwachman-Bodian-Diamond Syndrome Protein SBDS. International journal of molecular sciences 5 35887285
2019 The Acanthamoeba SBDS, a cytoskeleton-associated gene, is highly expressed during phagocytosis and encystation. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 5 31882330
2011 Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome. PloS one 5 21695142
2024 SBDS Gene Mutation Increases ROS Production and Causes DNA Damage as Well as Oxidation of Mitochondrial Membranes in the Murine Myeloid Cell Line 32Dcl3. Biological & pharmaceutical bulletin 4 39085077
2022 SBDS interacts with RNF2 and is degraded through RNF2-dependent ubiquitination. Biochemical and biophysical research communications 4 35158210
2008 Expression of the Shwachman-Bodian-Diamond syndrome (SBDS) protein in human pancreatic cancer and chronic pancreatitis. Histology and histopathology 4 18437680
2022 Improved detection of SBDS gene mutation by a new method of next-generation sequencing analysis based on the Chinese mutation spectrum. PloS one 3 36512530
2022 Two mutations in the SBDS gene reveal a diagnosis of Shwachman-Diamond syndrome in a patient with atypical symptoms. Cold Spring Harbor molecular case studies 3 36577524
2008 Characterization of the Trypanosoma cruzi ortholog of the SBDS protein reveals an intrinsically disordered extended C-terminal region showing RNA-interacting activity. Biochimie 3 19121363
2023 SBDSR126T rescues survival of sbds zebrafish in a dose-dependent manner independently of Tp53. Life science alliance 2 37816584
2007 Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children. Haematologica 2 18024409
2025 Prenatal Diagnosis of Shwachman-Diamond Syndrome: Fetal Compound Heterozygous Variants in the SBDS Gene Associated With Mildly Straight Ribs. Prenatal diagnosis 1 40011201
2024 Knockdown of the Shwachman-Diamond syndrome gene, SBDS, induces galectin-1 expression and impairs cell growth. International journal of hematology 1 38240987
2023 Site-specific labeling of SBDS to monitor interactions with the 60S ribosomal subunit. Methods (San Diego, Calif.) 1 36781034
2023 M phase-specific interaction between SBDS and RNF2 at the mitotic spindles regulates mitotic progression. Biochemical and biophysical research communications 1 37806249
2022 Case Report: Heterozygous Germline Variant in EIF6 Additional to Biallelic SBDS Pathogenic Variants in a Patient With Ribosomopathy Shwachman-Diamond Syndrome. Frontiers in genetics 1 36035165
2021 Evolutionary and functional relationships in the ribosome biogenesis SBDS and EFL1 protein families. Molecular genetics and genomics : MGG 1 34453201
2025 Clinical and genetic spectrum of SBDS and DNAJC21 gene variants in bone marrow failure cases: Atypical and cryptic presentations. Blood cells, molecules & diseases 0 40209608
2025 Structural Implications of Missense Point Mutations in Shwachman-Bodian-Diamond Syndrome Protein (SBDS): A Combined SAXS/MD Investigation. ACS omega 0 40821528
2025 Students with disabilities (SWDs) use of assistive technology in higher education institutions in Tanzania. Disability and rehabilitation. Assistive technology 0 41388820
2024 [Genetic and clinical analysis of a child with Shwachman-Diamond syndrome due to compound heterozygous variants of SBDS gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 38311561

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