Affinage

SRP14

Signal recognition particle 14 kDa protein · UniProt P37108

Round 2 corrected
Length
136 aa
Mass
14.6 kDa
Annotated
2026-04-28
93 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRP14 is a core subunit of the signal recognition particle (SRP) that, as an obligate heterodimer with SRP9, assembles the Alu domain of the SRP ribonucleoprotein to couple signal sequence recognition with translational elongation arrest, thereby maintaining nascent secretory polypeptides in a translocation-competent state during ER targeting (PMID:2153922, PMID:18455985). The SRP9/14 heterodimer binds the 5′ and 3′ terminal sequences of 7SL RNA through a positively charged concave β-sheet surface; the C-terminus of SRP14 and a KRDKK motif, together with SRP9 α2-helix lysines, form electrostatic contacts at the ribosomal subunit interface that are specifically required for elongation arrest (PMID:11089964, PMID:20348448, PMID:9115358). In primate cells, SRP9/14 exists in large cytoplasmic excess over assembled SRP, associates with Alu RNAs and BC200 RNA, localizes to the nucleus where it co-transcriptionally regulates 7SL and BC200 RNA expression, and is downregulated during ER stress via a PERK–eIF2α axis to attenuate protein translocation as a protective arm of the unfolded protein response (PMID:7542942, PMID:37156570, PMID:38943644). SRP14 also serves as a host factor exploited by viruses: it binds HIV-1 tat mRNA to modulate Tat-mediated transactivation and HIV latency, and interacts with PRRSV Nsp2 to promote viral genome synthesis (PMID:34194479, PMID:35293774).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1989 High

    Identification of SRP14 as a distinct SRP protein subunit established the molecular identity of the 14-kDa component and enabled subsequent reconstitution and structure–function studies.

    Evidence PCR-based cDNA cloning from human cells

    PMID:2557625

    Open questions at the time
    • No functional data beyond identification; activity of the isolated protein was unknown
  2. 1990 High

    Demonstrating that SRP9 and SRP14 form a heterodimer required for both SRP RNA binding and elongation arrest activity resolved the question of how the Alu domain is assembled and activated.

    Evidence In vitro reconstitution with purified components, RNA-binding assays, cell-free elongation arrest assays

    PMID:2153922

    Open questions at the time
    • Structural basis of heterodimerization and RNA recognition unknown
    • Mechanism by which the heterodimer contacts the ribosome not determined
  3. 1994 High

    Genetic disruption in S. cerevisiae showed that Srp14p is required in vivo for SRP stability and efficient ER translocation, establishing physiological essentiality beyond cell-free systems, while permuted fusion constructs demonstrated that N/C-terminal sequences are dispensable for core folding and RNA binding.

    Evidence Yeast gene disruption with translocation and growth phenotypes; recombinant SRP9-SRP14 fusion with binding and translocation assays

    PMID:7518078 PMID:7925282

    Open questions at the time
    • Whether yeast Srp14p mediates elongation arrest in vivo was untested
    • Atomic-level structure not yet available
  4. 1995 High

    Discovery that SRP9/14 exists in >20-fold molar excess in primate cells and associates with Alu RNAs revealed functions beyond SRP assembly, while comparative genomics linked an anthropoid-specific alanine-rich C-terminal expansion to increased protein abundance and Alu RNA-binding activity.

    Evidence Quantitative immunoblotting, immunoprecipitation, sucrose gradient fractionation; comparative genomics and binding assays across species

    PMID:7534378 PMID:7542942

    Open questions at the time
    • Functional consequence of Alu RNA binding by free SRP9/14 unknown
    • Whether the alanine tail is causal for increased abundance not formally tested
  5. 1997 High

    The crystal structure of SRP9/14, together with systematic mutagenesis and RNA minimal-domain mapping, defined the αββββα Alu-binding module fold, the saddle-shaped positively charged RNA-binding surface, and the 86-nt minimal Alu RNA folding domain, establishing the structural framework for understanding SRP Alu domain assembly.

    Evidence X-ray crystallography at 2.5 Å; site-directed mutagenesis with binding assays; ribozyme-generated RNA truncations with competition binding

    PMID:9214658 PMID:9233785 PMID:9409618

    Open questions at the time
    • RNA-bound structure not yet solved
    • Structural basis of the C-terminal elongation arrest function unresolved
  6. 1997 High

    Truncation of the SRP14 C-terminus abolished elongation arrest without affecting signal recognition or targeting, pinpointing this region as the specific effector of ribosome pausing and revealing associated conformational changes in SRP RNA.

    Evidence Reconstitution with truncated SRP14 (SRP14-20C), in vitro elongation arrest and translocation assays, chemical probing of RNA structure

    PMID:9115358

    Open questions at the time
    • Precise ribosomal contacts of the C-terminus undefined
    • Whether the RNA conformational change is obligatory for arrest unknown
  7. 2000 High

    Co-crystal structures of SRP9/14 with the 5′ and 5′+3′ RNA domains revealed the U-turn-based recognition of the conserved 5′ core and reversible docking of the 3′ domain, providing a mechanistic model for how the Alu domain might toggle between conformational states during the translational arrest cycle; simultaneously, yeast studies confirmed that Srp14p C-terminal-dependent elongation arrest is conserved and physiologically important.

    Evidence X-ray crystallography of two RNA-bound complexes; yeast SRP purification, in vitro arrest assays, in vivo growth/translocation phenotypes of C-terminal truncations

    PMID:10921896 PMID:11089964

    Open questions at the time
    • Structure of the SRP Alu domain on the ribosome not available
    • How 3′ domain reversibility is regulated during targeting unclear
  8. 2004 High

    Cross-linking showed that SRP14 repositions from a large-subunit contact to the ribosomal subunit interface upon signal sequence recognition, providing the first direct evidence for how the Alu domain physically reaches the elongation-factor binding site to arrest translation.

    Evidence Chemical protein cross-linking in signal-sequence-dependent cell-free translation complexes

    PMID:14705936

    Open questions at the time
    • Identities of specific ribosomal protein contacts not fully resolved
    • Cryo-EM validation at the interface not yet performed
  9. 2008 High

    SRP14 knockdown and complementation in mammalian cells demonstrated that elongation arrest is essential in vivo to buffer limiting SRP receptor concentration, unifying the biochemical arrest function with cellular secretory pathway fidelity.

    Evidence siRNA depletion, complementation with elongation-arrest-deficient SRP14 mutants, SRP receptor overexpression rescue, cell growth assays

    PMID:18455985

    Open questions at the time
    • Whether elongation arrest rates are dynamically regulated in response to secretory load unknown
    • Contribution of excess SRP9/14 pool to this buffering not addressed
  10. 2010 High

    Identification of the KRDKK motif on SRP14 and SRP9 α2 lysines as the essential electrostatic contacts for elongation arrest mapped the ribosome-interaction surface to one face of the heterodimer, completing the molecular picture of how SRP9/14 arrests the ribosome.

    Evidence Systematic site-directed mutagenesis validated in cell-free and mammalian cell-based assays

    PMID:20348448

    Open questions at the time
    • No high-resolution structure of SRP9/14 at the ribosomal subunit interface
    • Whether specific rRNA nucleotides are contacted remains unresolved
  11. 2021 Medium

    Discovery that SRP14 binds HIV-1 tat mRNA at the TIM-TAM element and modulates Tat-mediated transactivation and viral latency revealed an unexpected role as a host RNA-binding factor exploited by retroviruses, extending SRP14 function beyond the canonical SRP pathway.

    Evidence MS2-affinity purification coupled to mass spectrometry, luciferase reporters, RNA footprinting, SRP14 overexpression in primary CD4+ T cells from ART patients

    PMID:34194479

    Open questions at the time
    • Structural basis of SRP14-tat mRNA interaction not determined
    • Whether this function depends on SRP9 co-binding unknown
    • Independent replication in a second lab needed
  12. 2023 Medium

    Demonstration that SRP9/14 localizes to the nucleus and transcriptionally regulates 7SL and BC200 RNA genes established a feedforward loop in which the heterodimer controls the expression of its own RNA substrates.

    Evidence Immunofluorescence, subcellular fractionation, transcriptional run-on assays under SRP9/14 knockdown

    PMID:37156570

    Open questions at the time
    • Mechanism of nuclear import of SRP9/14 unknown
    • Whether transcriptional regulation is direct (DNA/chromatin binding) or indirect not resolved
    • Single-lab observation
  13. 2024 High

    Identification of a PERK–eIF2α–SRP14 axis during ER stress established that SRP14 downregulation mediates translocational attenuation as a protective UPR branch, directly linking SRP function to stress-responsive proteostasis; concurrently, U-turn-dependent recognition was validated as obligatory for Alu RNA–SRP9/14 association and BC200 expression.

    Evidence Multi-omics analysis, SRP14 overexpression/mutant rescue during ER stress, translocation reporters; SAXS and mutagenesis of Alu RNA pseudoknot

    PMID:38943644 PMID:40345827

    Open questions at the time
    • Whether PERK-mediated SRP14 reduction is tissue-specific in vivo not tested
    • Structural details of the non-canonical Alu RNA fold that escapes SRP9/14 binding are incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of the SRP Alu domain at the ribosomal subunit interface, the physiological functions of the large excess cytoplasmic SRP9/14–Alu RNA pool, the mechanism of SRP9/14 nuclear import and its mode of transcriptional regulation, and whether lysosomal targeting of SRP RNA via the Alu domain constitutes a regulated quality-control pathway.
  • No cryo-EM structure of SRP Alu domain engaged at the ribosome elongation-factor site
  • Functional significance of SRP9/14–Alu RNA complexes in the cytoplasm remains speculative
  • Lysosomal targeting observation awaits peer review

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0045182 translation regulator activity 5 GO:0005198 structural molecule activity 3
Localization
GO:0005829 cytosol 3 GO:0005840 ribosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-9609507 Protein localization 4 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
7SL RNABC200 RNASRP54SRP9
Complex memberships
SRP9/14 heterodimerSRP9/14–Alu RNA RNPSignal recognition particle (SRP)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 SRP14 cDNA was isolated encoding the 14-kDa subunit of the signal recognition particle, establishing it as one of six protein components of the SRP ribonucleoprotein complex. PCR-based cDNA cloning with cross-hybridization strategy Proceedings of the National Academy of Sciences of the United States of America High 2557625
1990 SRP9 and SRP14 form a heterodimer that is required for specific binding to SRP RNA; neither protein alone can bind SRP RNA, and heterodimerization occurs independently of RNA. Both proteins are required to reconstitute the elongation arrest function of the Alu domain. In vitro reconstitution, RNA-binding assays, cell-free translation/elongation arrest assay Molecular and cellular biology High 2153922
1994 SRP9 and SRP14 can be expressed as a single fused polypeptide chain (permuted fusion) that folds into a heterodimer-like structure, binds SRP RNA as a monomer, and confers both elongation arrest and translocation activities, demonstrating that the N- and C-termini of both proteins are dispensable for folding and RNA-binding. Recombinant fusion protein expression, RNA-binding assays, in vitro elongation arrest and translocation assays Nucleic acids research High 7518078
1994 In yeast Saccharomyces cerevisiae, Srp14p is an SRP subunit whose disruption causes slow growth and inefficient ER translocation. Srp14p is required for stable expression of the yeast SRP; loss of Srp14p reduces SRP RNA and protein levels, unlike loss of Srp54p or Sec65p. Immunoaffinity purification, gene disruption, translocation assays The EMBO journal High 7925282
1995 In primate cells, SRP9/14 is present in over 20-fold molar excess over assembled SRP. The excess SRP9/14 is predominantly cytoplasmic and not bound to SRP RNA, but a significant fraction associates with small cytoplasmic Alu RNAs in an 8.5S RNP, indicating roles beyond SRP assembly. Immunoprecipitation with SRP9/SRP14 antibodies, sucrose gradient sedimentation, quantitative immunoblotting Molecular biology of the cell High 7542942
1995 In anthropoid primates, the SRP14 gene acquired a GCA trinucleotide repeat in its 3'-coding region producing an extended C-terminal alanine-rich tail. This repeat expansion is associated with increased SRP14 protein abundance and increased Alu RNA-binding activity in anthropoids compared to rodents. Comparative genomics, gene cloning, binding assays Molecular and cellular biology Medium 7534378
1996 Dimeric Alu RNAs induced by adenovirus infection are assembled into SRP9/14-containing RNPs in vivo, while SRP levels remain unchanged, demonstrating that SRP9/14 binds both the stable left-monomer scAlu RNA and nascent dimeric Alu transcripts in living cells. Immunoprecipitation with anti-SRP9 antiserum, Northern blotting Nucleic acids research Medium 8932367
1997 Crystal structure of the mouse SRP9/14 heterodimer determined at 2.5 Å resolution revealed that both subunits share the same α-β-β-β-α fold (designated the Alu binding module), assemble with pseudo-2-fold symmetry into a saddle-shaped structure with a curved six-stranded amphipathic β-sheet, and present a positively charged concave surface for RNA binding. X-ray crystallography at 2.5 Å resolution The EMBO journal High 9233785
1997 A C-terminal truncation of SRP14 (SRP14-20C) forms a stable complex with SRP9 and SRP RNA but completely abolishes elongation arrest activity without affecting signal recognition, targeting, or ribosome binding, demonstrating that the C-terminus of SRP14 specifically mediates ribosome interactions required for elongation arrest and that this truncation causes tertiary structural changes in SRP RNA. In vitro reconstitution, elongation arrest assays, chemical probing of RNA structure Nucleic acids research High 9115358
1997 Human SRP9/14 binds with higher affinity than mouse SRP9/14 to all Alu-like RNAs tested (including BC200 RNA and neuron-specific RNAs), independently of the C-terminal alanine-rich extension, suggesting that the core heterodimer evolved increased affinity in anthropoids. Quantitative equilibrium competition binding assays with recombinant proteins Nucleic acids research Medium 9016560
1997 Mutational analysis identified RNA-binding determinants: acidic residues in the N-terminal α-helix of SRP9 and a flexible internal loop region in SRP14 are critical for RNA binding. The dimerization requirements differ substantially between SRP9 and SRP14; SRP14 tolerates fewer changes without losing dimerization activity. In vitro mutagenesis, dimerization and RNA-binding assays RNA (New York, N.Y.) High 9214658
1997 A minimal 86-nucleotide Alu RNA folding domain (SA86) was identified that competes efficiently with 7SL RNA for SRP9/14 binding and contains two stem-loops connected by a conserved bulge plus a central adaptor stem; this domain functions as an autonomous RNA folding unit, suggesting Alu RNA identity is determined by a characteristic tertiary structure. Ribozyme-generated RNA variants, quantitative equilibrium competition binding assay RNA (New York, N.Y.) High 9409618
1998 SRP9 protein (and by implication SRP9/14 heterodimer) associates with BC200 RNA in primate brain neurons in vivo, as demonstrated by immunoprecipitation with anti-SRP9 antibody, indicating that the neuronal BC200 RNP is a candidate for regulating local dendritic protein synthesis via a translation arrest-like mechanism. Immunoprecipitation with anti-SRP9 antibody from brain tissue Neuroscience letters Medium 9605471
1999 In S. cerevisiae, Srp14p binds as a homodimer (not a heterodimer) to the 5' sequences of scR1 RNA; its minimal binding site is 99 nt comprising a short hairpin and extended stem. The conserved UGUAAU motif and basic amino acid residues are essential for RNA binding, confirming common ancestry with mammalian SRP14 despite substantial changes in RNA-protein recognition. RNA footprinting, site-directed mutagenesis, RNA-binding assays RNA (New York, N.Y.) High 10573124
2000 Crystal structures of the SRP9/14 heterodimer bound to the 5' domain alone or to a construct containing both 5' and 3' domains of SRP RNA revealed that SRP9/14 binds strongly to the conserved core 5' domain forming a U-turn, and the 3' domain docks more weakly and reversibly; this reversibility may be mechanistically important for translational regulation. X-ray crystallography; two crystal structures solved Nature High 11089964
2000 Yeast SRP has elongation arrest activity dependent on the C-terminus of Srp14p. A C-terminal truncation (ΔC29) abolishes elongation arrest and substantially reduces translocation efficiency in vitro, and confers temperature-sensitive growth in vivo, demonstrating that elongation arrest is a physiologically important and conserved function of eukaryotic SRP. Yeast SRP purification, in vitro elongation arrest assay, in vivo growth and translocation assays The EMBO journal High 10921896
2001 Biochemical and biophysical analysis demonstrated a hierarchical assembly of the SRP Alu domain: SRP9 and SRP14 first heterodimerize, then bind the Alu RNA 5' domain, which creates a binding site for the 3' domain; the 3' domain then folds back 180° onto the 5' domain complex to form the compact Alu RNP. This final step is likely reversible. Biochemical assembly assays, small-angle neutron scattering (SANS), analytical ultracentrifugation RNA (New York, N.Y.) High 11350037
2004 Protein cross-linking experiments showed that SRP14 (Alu domain) is in close physical proximity to ribosomal proteins in functional SRP-ribosome complexes. Without a signal sequence, SRP14 cross-links to a large-subunit protein; upon signal sequence recognition, the Alu domain repositions to the ribosomal subunit interface, cross-linking to proteins of both large and small subunits. Chemical protein cross-linking in cell-free translation complexes, SDS-PAGE analysis Biochemistry High 14705936
2008 SRP14 depletion in mammalian cells prevents efficient protein translocation into the ER due to rate-limiting SRP receptor concentrations. Complementation with elongation-arrest-deficient SRP14 mutants caused defective secretion, depletion of endogenous membrane proteins, and reduced cell growth; these defects were reversed by slowing global translation or increasing SRP receptor expression, demonstrating that the elongation arrest function of SRP14 is essential to keep nascent chains translocation-competent during targeting. siRNA depletion, complementation with SRP14 mutants, ER translocation assays, cell growth assays, SRP receptor overexpression rescue Cell High 18455985
2008 APOBEC3G associates with 7SL RNA via its Alu domain structure. RNAi knockdown of SRP14 prevented 7SL RNA from accessing HIV virions but did not block APOBEC3F or APOBEC3G recruitment into virions, demonstrating that 7SL RNA is not an essential mediator of APOBEC3 virion packaging. RNA interference, HIV virion incorporation assays, immunoprecipitation Retrovirology Medium 18597676
2009 Crystal structure of S. pombe SRP14 (SpSRP14) showed it crystallizes as a homodimer, and comparison with human SRP9/14-Alu RNA complex suggests many protein-RNA contacts centered on the conserved U-turn motif are conserved in fission yeast despite the absence of SRP9. X-ray crystallography using RIP (radiation-damage-induced phasing) and SAD phasing Acta crystallographica. Section D, Biological crystallography High 19390147
2010 Mutational analysis of human SRP9/14 identified two patches of basic residues essential for elongation arrest: one patch includes the KRDKK pentapeptide (replaceable by four lysines), and a second includes three lysines in the α2 helix of SRP9. All essential residues cluster on one face of the heterodimer and likely interact electrostatically with ribosomal RNA phosphate backbone. Site-directed mutagenesis, in vitro elongation arrest assays, mammalian cell-based translocation assays RNA (New York, N.Y.) High 20348448
2013 Overexpression of human SRP14 (along with other secretory pathway components) in CHO cells rescued translational arrest and improper processing of a difficult-to-express immunoglobulin light chain, restoring its proper translocation and assembly, demonstrating that SRP14 can be limiting for secretory protein expression. CHO cell engineering, overexpression of SRP14, protein secretion and assembly assays Metabolic engineering Medium 23380542
2017 miR-10a-5p directly targets the 3'UTR of SRP14 mRNA and suppresses SRP14 protein expression via translational repression (not mRNA degradation); knockdown of SRP14 by siRNA inhibits PRRSV replication, identifying SRP14 as a host factor required for PRRSV replication. miRNA mimics, luciferase 3'UTR reporter assays, siRNA knockdown, viral replication assays The Journal of general virology Medium 28086075
2021 SRP14 binds to tat mRNA at the TIM-TAM conserved RNA sequence-structure element (a Tat IRES modulator). Knockdown of SRP14 negatively affected tat mRNA processing and translation, reduced Tat-mediated transactivation, and increased HIV-1 latency. Overexpression of SRP14 in resting CD4+ T cells from patients on ART was sufficient to reverse HIV-1 latency and induce virus production. Affinity purification coupled with MS (MS2-tagged tat mRNA), luciferase reporter assays, RNA footprinting, overexpression in primary T cells, dual-color HIV reporter virus infections Frontiers in genetics Medium 34194479
2022 Transcription factor IRF8 negatively regulates miR-10a expression; PRRSV infection decreases IRF8, upregulating miR-10a which suppresses SRP14. SRP14 promotes PRRSV genome synthesis by directly interacting with the viral non-structural protein Nsp2, establishing an IRF8-miR-10a-SRP14 regulatory pathway in antiviral innate immunity. siRNA knockdown, overexpression, co-immunoprecipitation of SRP14-Nsp2, viral replication assays, luciferase reporter assays Journal of virology Medium 35293774
2023 SRP9/14 heterodimer localizes to the nucleus (demonstrated by immunofluorescence and subcellular fractionation) and transcriptionally regulates 7SL and BC200 RNA expression. SRP9/14 knockdown altered steady-state levels and transcriptional activity at 7SL and BC200 genes, suggesting a co-transcriptional regulatory role. Immunofluorescent imaging, subcellular fractionation, RNA steady-state and decay measurements, transcriptional run-on assays under SRP9/14 knockdown RNA (New York, N.Y.) Medium 37156570
2024 During ER stress, SRP14 protein levels are markedly reduced via PERK-mediated eIF2α phosphorylation (but independently of ATF4/ATF3). This reduction correlates with decreased protein translocation into the ER (translocational attenuation). Enforced expression of elongation-arrest-competent SRP14 prevents reduced translocation of cathepsin D, while an elongation-arrest-deficient mutant does not; SRP14 overexpression augments UPR and aggravates ER-stress-induced cell death, identifying a PERK-SRP14 axis as a protective UPR mechanism. Multi-omics analysis, Western blotting, translocation reporter assays, SRP14 overexpression/mutant rescue, ER stress induction Cell reports High 38943644
2024 The SRP9/SRP14 interaction with the Alu RNA pseudoknot is dependent on a U-turn motif; mutation of a critical guanosine in BC200's pseudoknot significantly reduces BC200 expression. A short Alu RNA (EB120) lacking the canonical U-turn triad adopts a non-canonical fold (confirmed by SAXS and computational structure prediction) and fails to associate with SRP9/14 in cellular context. Site-directed mutagenesis, cell-line expression profiling, immunoprecipitation, small-angle X-ray scattering (SAXS), computational structure prediction RNA (New York, N.Y.) High 40345827
2025 The Alu domain of SRP RNAs (dependent on SRP9 and SRP14 protein interactions) is sufficient to target SRP RNAs to lysosomes for degradation via autophagy, identifying SRP9/14-mediated Alu domain recognition as a selectivity signal for lysosomal RNA targeting. Lysosomal RNA profiling, RNase identification, autophagy inhibition, Alu domain mutant constructs bioRxivpreprint Medium 40964324

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2005 Nucleolar proteome dynamics. Nature 934 15635413
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2014 A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 325 25036637
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2022 EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Molecular cancer 257 35031058
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2017 Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nature communications 221 28524877
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2023 The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nature genetics 182 36914876
2000 Structure and assembly of the Alu domain of the mammalian signal recognition particle. Nature 152 11089964
2013 CHO cell engineering to prevent polypeptide aggregation and improve therapeutic protein secretion. Metabolic engineering 115 23380542
2008 SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites. Cell 112 18455985
1994 Subunits of the Saccharomyces cerevisiae signal recognition particle required for its functional expression. The EMBO journal 104 7925282
2000 Elongation arrest is a physiologically important function of signal recognition particle. The EMBO journal 98 10921896
2003 SRPDB: Signal Recognition Particle Database. Nucleic acids research 94 12520023
2006 The tmRDB and SRPDB resources. Nucleic acids research 88 16381838
1990 Assembly of the Alu domain of the signal recognition particle (SRP): dimerization of the two protein components is required for efficient binding to SRP RNA. Molecular and cellular biology 74 2153922
2008 Characterization of APOBEC3G binding to 7SL RNA. Retrovirology 65 18597676
2015 Genetic ablation of ataxin-2 increases several global translation factors in their transcript abundance but decreases translation rate. Neurogenetics 58 25721894
1995 The SRP9/14 subunit of the signal recognition particle (SRP) is present in more than 20-fold excess over SRP in primate cells and exists primarily free but also in complex with small cytoplasmic Alu RNAs. Molecular biology of the cell 53 7542942
2014 Plasmodium falciparum signal recognition particle components and anti-parasitic effect of ivermectin in blocking nucleo-cytoplasmic shuttling of SRP. Cell death & disease 49 24434517
2008 Genomic selection of reference genes for real-time PCR in human myocardium. BMC medical genomics 49 19114010
1996 Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells. Nucleic acids research 49 8932367
2001 SRPDB (Signal Recognition Particle Database). Nucleic acids research 47 11125080
1997 The crystal structure of the signal recognition particle Alu RNA binding heterodimer, SRP9/14. The EMBO journal 46 9233785
1997 The SRP9/14 subunit of the human signal recognition particle binds to a variety of Alu-like RNAs and with higher affinity than its mouse homolog. Nucleic acids research 45 9016560
2004 Identification and comparative analysis of components from the signal recognition particle in protozoa and fungi. BMC genomics 41 14720308
1997 A truncation in the 14 kDa protein of the signal recognition particle leads to tertiary structure changes in the RNA and abolishes the elongation arrest activity of the particle. Nucleic acids research 40 9115358
2010 Residues in SRP9/14 essential for elongation arrest activity of the signal recognition particle define a positively charged functional domain on one side of the protein. RNA (New York, N.Y.) 38 20348448
1998 Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain. Neuroscience letters 37 9605471
2001 Hierarchical assembly of the Alu domain of the mammalian signal recognition particle. RNA (New York, N.Y.) 35 11350037
1998 The Signal Recognition Particle Database (SRPDB). Nucleic acids research 35 9399828
2019 Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci. Cancers 34 31561579
1997 Identification of a minimal Alu RNA folding domain that specifically binds SRP9/14. RNA (New York, N.Y.) 29 9409618
2004 Signal recognition particle Alu domain occupies a defined site at the ribosomal subunit interface upon signal sequence recognition. Biochemistry 26 14705936
1989 Isolation of a cDNA clone of the 14-kDa subunit of the signal recognition particle by cross-hybridization of differently primed polymerase chain reactions. Proceedings of the National Academy of Sciences of the United States of America 26 2557625
2017 Cellular microRNA miR-10a-5p inhibits replication of porcine reproductive and respiratory syndrome virus by targeting the host factor signal recognition particle 14. The Journal of general virology 25 28086075
1995 A trinucleotide repeat-associated increase in the level of Alu RNA-binding protein occurred during the same period as the major Alu amplification that accompanied anthropoid evolution. Molecular and cellular biology 25 7534378
1999 The Alu domain homolog of the yeast signal recognition particle consists of an Srp14p homodimer and a yeast-specific RNA structure. RNA (New York, N.Y.) 24 10573124
2007 Unraveling the components of protein translocation pathway in human malaria parasite Plasmodium falciparum. Archives of biochemistry and biophysics 23 17919451
1994 The heterodimeric subunit SRP9/14 of the signal recognition particle functions as permuted single polypeptide chain. Nucleic acids research 23 7518078
2022 Host Cells Actively Resist Porcine Reproductive and Respiratory Syndrome Virus Infection via the IRF8-MicroRNA-10a-SRP14 Regulatory Pathway. Journal of virology 21 35293774
2021 Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components. Frontiers in molecular biosciences 20 34113652
1996 The Signal Recognition Particle Database (SRPDB). Nucleic acids research 17 8594607
2007 A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Molecular pharmacology 16 18089836
2021 A reciprocal feedback loop between HIF-1α and HPIP controls phenotypic plasticity in breast cancer cells. Cancer letters 15 34767928
2011 Establishing reference genes for use in real-time quantitative PCR analysis of early equine embryos. Reproduction, fertility, and development 12 21211469
1997 The Signal Recognition Particle Database (SRPDB). Nucleic acids research 12 9016514
2021 The RNA-Binding Proteins SRP14 and HMGB3 Control HIV-1 Tat mRNA Processing and Translation During HIV-1 Latency. Frontiers in genetics 11 34194479
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1996 The sequence of a 16,691 bp segment of Saccharomyces cerevisiae chromosome IV identifies the DUN1, PMT1, PMT5, SRP14 and DPR1 genes, and five new open reading frames. Yeast (Chichester, England) 9 8923743
2024 Characterised intron retention profiles in muscle tissue of idiopathic inflammatory myopathy subtypes. Annals of the rheumatic diseases 6 38302260
2019 Selection of reference genes for quantitative studies in acute myeloid leukaemia. The Malaysian journal of pathology 6 31901916
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2024 Translocational attenuation mediated by the PERK-SRP14 axis is a protective mechanism of unfolded protein response. Cell reports 5 38943644
2024 The role of SRP9/SRP14 in regulating Alu RNA. RNA biology 5 39563162
2023 Nuclear SRP9/SRP14 heterodimer transcriptionally regulates 7SL and BC200 RNA expression. RNA (New York, N.Y.) 5 37156570
2025 Deciphering Immunometabolic Landscape in Rheumatoid Arthritis: Integrative Multiomics, Explainable Machine Learning and Experimental Validation. Journal of inflammation research 4 39835297
2003 Advances in the structure and functions of signal recognition particle in protein targeting. Journal of biological regulators and homeostatic agents 4 15065758
2024 The P124A mutation of SRP14 alters its migration on SDS-PAGE without impacting its function. Acta biochimica et biophysica Sinica 3 38273782
2025 Lysosomal RNA profiling reveals targeting of specific types of RNAs for degradation. bioRxiv : the preprint server for biology 2 40964324
2024 Higher expression of TSR2 aggravating hypertension via the PPAR signaling pathway. Aging 2 38814181
2025 Discovery of myeloid zinc finger (MZF) 1 nuclear bodies. Biochemical and biophysical research communications 1 39954358
2024 Exploring potential causal genetic variants and genes for endometrial cancer: Open Targets Genetics, Mendelian randomization, and multi-tissue transcriptome-wide association analysis. Translational cancer research 1 39697733
2023 Genome-wide analysis of circRNA regulation during spleen development of Chinese indigenous breed Meishan pigs. BMC genomics 1 37612620
2026 Investigation of gene stability in equine luteal tissue during mid-diestrus phase and early pregnancy - Research Article. BMC veterinary research 0 41507934
2025 Alu RNA pseudoknot alterations influence SRP9/SRP14 association. RNA (New York, N.Y.) 0 40345827
2025 Integrated transcriptomic and single-cell RNA sequencing identifies lysosomal ion channel genes as potential biomarkers for Alzheimer's disease. Frontiers in genetics 0 41132791
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2024 Expression of signal recognition particle 14 in hepatocellular carcinoma and its relationship with disease progression and patient survival. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 0 39183055