Affinage

TTC5

Tetratricopeptide repeat protein 5 · UniProt Q8N0Z6

Length
440 aa
Mass
48.9 kDa
Annotated
2026-04-28
91 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TTC5 (also known as STRAP) is a TPR/OB-fold scaffold protein that functions as a tubulin-specific cotranslational quality control factor and as a multivalent signaling adaptor across several major cellular pathways. In its tubulin autoregulatory role, TTC5 binds near the ribosome exit tunnel to recognize nascent tubulin N-termini and triggers tubulin mRNA degradation when soluble αβ-tubulin levels are elevated; under basal conditions, soluble tubulins sequester TTC5 via its flexible C-terminal tail, keeping this activity suppressed, and loss of this autoregulation causes chromosome segregation defects (PMID:31727855, PMID:39551769). As a signaling scaffold, TTC5 inhibits TGF-β signaling by recruiting Smad7 to activated type I receptors (PMID:9856985, PMID:10757800), potentiates p53 transcriptional activity by displacing Mdm2 and localizing to chromatin of p53 target genes under DNA damage-induced ATM/Chk2 phosphorylation (PMID:17916563, PMID:18833288, PMID:22362889), promotes Wnt/β-catenin signaling by binding GSK3β to protect β-catenin from destruction complex-mediated degradation (PMID:26910283), and participates in U2 snRNP assembly to regulate alternative splicing of transcripts critical for nervous system development (PMID:33230114). TTC5 also forms a complex with Csde1 to couple mRNA decay with translation, as demonstrated for Bach2 mRNA during plasma cell differentiation (PMID:40133358), and negatively regulates autophagy by antagonizing JMY-mediated actin nucleation at phagophore membranes (PMID:30593260).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Identification of TTC5 (STRAP) as a TGF-β receptor-interacting protein established it as a negative regulator of TGF-β signaling, opening investigation into its scaffold function.

    Evidence Yeast two-hybrid screen and co-immunoprecipitation with TβR-I/II plus transcriptional reporter assays in mammalian cells

    PMID:9856985

    Open questions at the time
    • Mechanism of inhibition at the receptor level was not defined
    • No structural data on how STRAP contacts the receptors
  2. 2000 High

    The mechanism of TGF-β inhibition was resolved: STRAP recruits Smad7 specifically to the activated type I receptor, forming a ternary complex that blocks Smad2/3 access, and STRAP itself is phosphorylated in a receptor kinase-dependent manner.

    Evidence Co-immunoprecipitation showing ternary complex, reporter assays, in vivo phosphorylation analysis

    PMID:10757800

    Open questions at the time
    • Identity of the specific phosphorylated residue on STRAP was not mapped
    • In vivo relevance in animal models was not tested
  3. 2007 High

    Discovery that TTC5 directly binds p53's DNA-binding domain and displaces Mdm2 established a second major signaling axis — p53 activation — mechanistically distinct from TGF-β inhibition.

    Evidence Reciprocal co-immunoprecipitation, cysteine mutagenesis (Cys152/Cys270 on STRAP, Cys135 on p53), reporter and apoptosis assays

    PMID:17916563

    Open questions at the time
    • No structural basis for STRAP-p53 interaction
    • Relevance in DNA damage context not yet tested
  4. 2008 High

    The DNA damage-responsive regulation of TTC5 was established: ATM phosphorylation drives nuclear accumulation by blocking export, while Chk2 phosphorylation stabilizes nuclear TTC5, explaining how p53 coactivation is triggered by genotoxic stress.

    Evidence In vitro kinase assays, subcellular fractionation, protein stability assays

    PMID:18833288

    Open questions at the time
    • Exact phosphorylation sites on STRAP were not all mapped
    • Genetic epistasis in vivo was not performed
  5. 2011 Medium

    Binding of TTC5 to GSK3β and Axin, and stabilization of Notch3 intracellular domain via reduced ubiquitination, linked TTC5 to Wnt and Notch signaling pathways beyond TGF-β and p53.

    Evidence Co-immunoprecipitation and in vivo ubiquitination assays with GSK3β inhibitor controls

    PMID:21502811

    Open questions at the time
    • Structural basis for GSK3β interaction not determined
    • Wnt pathway functional consequences not shown in this study
    • Single-lab finding
  6. 2012 High

    The crystal structure of full-length TTC5 at 2.05 Å revealed an atypical six-TPR plus OB-fold architecture, explaining its capacity for diverse protein–protein and protein–DNA interactions, and both domains were shown to localize to chromatin of p53 target genes.

    Evidence X-ray crystallography, ChIP assays, functional mutagenesis

    PMID:22362889

    Open questions at the time
    • No co-crystal structures with any binding partner
    • How each domain individually contributes to different signaling axes was not dissected
  7. 2013 High

    TTC5 was shown to regulate collagen biosynthesis by tethering to collagen mRNAs via LARP6 and restraining translation of collagen α2(I) mRNA through interaction with eIF4A, revealing a translational regulatory function.

    Evidence Co-immunoprecipitation, polysome profiling, pulldown, functional rescue in STRAP-deficient cells

    PMID:23918805

    Open questions at the time
    • Whether TTC5 directly contacts mRNA or only acts through LARP6 was not resolved
    • Structural basis of eIF4A interaction unknown
  8. 2016 Medium

    TTC5 was established as a scaffold in innate immune signaling: it bridges TAK1, IKKα, and NF-κB p65 to facilitate p65 phosphorylation and nuclear translocation in TLR2/4 pathways, with subsequent nuclear TTC5 prolonging cytokine transcription.

    Evidence Co-immunoprecipitation, knockdown/overexpression with cytokine measurement, nuclear translocation assay

    PMID:27934954

    Open questions at the time
    • Single-lab study
    • No structural basis for multi-protein scaffold assembly
    • Relative contribution vs. other NF-κB scaffolds not assessed
  9. 2016 Medium

    Functional demonstration that TTC5 promotes Wnt/β-catenin signaling by binding GSK3β and preventing β-catenin phosphorylation and degradation, with consequences for CRC metastasis, extended the GSK3β interaction to a defined oncogenic pathway.

    Evidence Co-immunoprecipitation, ubiquitylation assay, in vitro and in vivo metastasis assays

    PMID:26910283

    Open questions at the time
    • Single-lab study
    • Whether TTC5 competes with Axin for GSK3β binding was not tested
  10. 2019 High

    A paradigm shift: TTC5 was identified as a tubulin-specific ribosome-associated quality control factor that binds near the exit tunnel, recognizes nascent tubulin N-termini, and triggers cotranslational mRNA degradation, with loss-of-function causing chromosome segregation defects.

    Evidence Structural analysis, in vitro biochemistry, mutagenesis ablating ribosome and nascent-chain interactions, mitotic phenotyping

    PMID:31727855

    Open questions at the time
    • Mechanism linking TTC5-nascent tubulin recognition to mRNA deadenylation machinery not defined
    • Whether other nascent chains besides tubulins are recognized was not tested
  11. 2019 Medium

    TTC5 was shown to negatively regulate autophagy by binding JMY and antagonizing its LC3-dependent recruitment to phagophore membranes and actin nucleation activity.

    Evidence In vitro reconstitution with membrane-bound LC3, co-immunoprecipitation, actin polymerization assay

    PMID:30593260

    Open questions at the time
    • In vivo relevance to autophagic flux not demonstrated in animal models
    • Whether TTC5-JMY interaction is regulated by tubulin levels is unknown
  12. 2020 High

    TTC5 was established as a spliceosome-associated factor involved in 17S U2 snRNP assembly; its deletion caused widespread alternative splicing changes preferentially targeting nervous system transcripts, and loss in Xenopus impaired neural tube closure.

    Evidence eCLIP-seq, RNA-seq splicing analysis, mouse embryoid body deletion model, Xenopus loss-of-function

    PMID:33230114

    Open questions at the time
    • Direct RNA-binding specificity of TTC5 versus indirect recruitment via U2 snRNP not resolved
    • Whether the splicing function is independent of the tubulin autoregulation role is unclear
  13. 2024 High

    The autoregulatory switch mechanism was resolved: soluble αβ-tubulins sequester TTC5 via its flexible C-terminal tail under normal conditions, preventing constitutive engagement of nascent tubulins at ribosomes; loss of this sequestration constitutively activates TTC5 and depletes tubulin mRNAs.

    Evidence Cryo-EM/structural proteomics, biochemical reconstitution, functional cell biology assays

    PMID:39551769

    Open questions at the time
    • Identity of the deadenylase/decay machinery recruited by active TTC5 remains unknown
    • Whether other factors modulate the C-terminal tail switch is untested
  14. 2025 High

    The Csde1–TTC5 complex was shown to couple Bach2 mRNA decay with translation during plasma cell differentiation, establishing TTC5 as a component of a post-transcriptional regulatory module controlling immune cell fate decisions.

    Evidence RNA interactome capture, CRISPR functional screen, RIP, RNA-seq, protein stability assays in B cells

    PMID:40133358

    Open questions at the time
    • Whether TTC5 contributes RNA-binding activity or acts solely as a scaffold within the Csde1 complex is not resolved
    • Generality to other Csde1-regulated transcripts beyond Bach2 not tested systematically
  15. 2025 High

    S-nitrosylation of TTC5 at Cys152 and Cys270 by iNOS was identified as a regulatory switch that disrupts TTC5-ASK1 interaction, activating the ASK1-MKK3-p38 apoptotic pathway, revealing redox-dependent control of TTC5 scaffold function.

    Evidence S-nitrosylation assay, cysteine mutagenesis, co-immunoprecipitation, kinase activity assay, apoptosis assay

    PMID:41519199

    Open questions at the time
    • Physiological contexts in which iNOS-mediated S-nitrosylation of TTC5 is triggered are not defined
    • Interplay between S-nitrosylation and other PTMs at the same cysteines is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the mRNA decay machinery recruited by TTC5 during tubulin autoregulation; whether the tubulin quality control and signaling scaffold functions operate through the same structural surfaces or are mutually exclusive; and whether TTC5's splicing role is mechanistically linked to its translational regulatory activities.
  • No reconstitution of the complete tubulin autoregulation pathway from TTC5 to deadenylation/decay factors
  • Structural basis for simultaneous engagement of multiple partners is unknown
  • Functional hierarchy among TTC5's diverse roles in vivo has not been established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5 GO:0003723 RNA binding 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005840 ribosome 2 GO:0005694 chromosome 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-5357801 Programmed Cell Death 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1
Partners
CSDE1GSK3BJMYLARP6MAP3K5SMAD7TGFBR1TP53
Complex memberships
17S U2 snRNPCsde1-Strap complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 TTC5 is a tubulin-specific ribosome-associating factor that binds near the ribosome exit tunnel and engages the amino terminus of nascent tubulins, triggering cotranslational degradation of tubulin mRNAs in response to excess soluble tubulin. TTC5 mutants incapable of ribosome or nascent tubulin interaction abolished tubulin autoregulation and showed chromosome segregation defects during mitosis. Structural analysis, in vitro biochemistry, mutagenesis, cell biology (chromosome segregation assay) Science High 31727855
2024 Under normal conditions, soluble αβ-tubulins bind to and sequester TTC5, preventing it from engaging nascent tubulins at translating ribosomes. The flexible C-terminal tail of TTC5 acts as a molecular switch toggling between soluble αβ-tubulin-bound and nascent tubulin-bound states. Loss of sequestration constitutively activates TTC5, leading to diminished tubulin mRNA levels and compromised chromosome segregation. Biochemical and structural proteomic approaches, cryo-EM/structural proteomics, functional cell biology assays Nature Communications High 39551769
1998 STRAP (TTC5) was identified as a WD40 domain-containing protein that interacts with both TGF-β type I (TβR-I) and type II (TβR-II) serine-threonine kinase receptors. Overexpression of STRAP inhibits TGF-β-mediated transcriptional activation and synergizes with Smad7 to inhibit TGF-β signaling. Yeast two-hybrid, co-immunoprecipitation, transcriptional reporter assays The Journal of Biological Chemistry High 9856985
2000 STRAP synergizes specifically with Smad7 (but not Smad6) to inhibit TGF-β signaling by recruiting Smad7 to the activated type I receptor, forming a ternary complex that stabilizes Smad7-receptor association and prevents Smad2/Smad3 access to the receptor. STRAP is phosphorylated in vivo in a TGF-β receptor kinase-dependent manner, requiring its C-terminus. Co-immunoprecipitation, transcriptional reporter assays, in vivo phosphorylation assay Molecular and Cellular Biology High 10757800
2012 Crystal structure of full-length STRAP (TTC5) at 2.05 Å resolution revealed an atypical six tetratricopeptide repeat (TPR) protein that also contains an unexpected oligonucleotide/oligosaccharide-binding (OB)-fold domain, providing an extended superhelical scaffold for protein-protein and protein-DNA interactions. Both TPR and OB-fold domains localize to chromatin of p53 target genes and exhibit intrinsic regulatory activity necessary for the Strap-dependent p53 response. X-ray crystallography, ChIP assay, functional mutagenesis Proceedings of the National Academy of Sciences of the USA High 22362889
2008 ATM kinase phosphorylates STRAP (TTC5), facilitating its nuclear accumulation by impeding nuclear export, while Chk2 phosphorylation augments STRAP protein stability once it has attained a nuclear location, thereby coordinating p53 transcriptional responses to DNA damage. In vitro kinase assay, subcellular fractionation, protein stability assay, functional reporter assays EMBO Reports High 18833288
2007 STRAP (TTC5) interacts directly with the central DNA binding domain of p53 (residues 113-290) via Cys152 (or Cys270) of STRAP and Cys135 of p53, potentiating p53 transcriptional activity, apoptosis, and growth inhibition by removing Mdm2 from the p53-Mdm2 complex. Co-immunoprecipitation, mutagenesis, reporter assays, apoptosis assays The Journal of Biological Chemistry High 17916563
2013 STRAP (TTC5) is tethered to collagen α1(I) and α2(I) mRNAs via interaction with the RNA-binding protein LARP6, and interacts with eIF4A to restrain translation of collagen α2(I) mRNA. Absence of STRAP causes unrestricted loading of collagen α2(I) mRNA onto polysomes, imbalanced synthesis of collagen chains, hypermodification of α1(I), and failure of collagen trimer assembly. Co-immunoprecipitation, polysome profiling, pulldown, functional rescue experiments Molecular and Cellular Biology High 23918805
2014 STRAP (TTC5) is phosphorylated at Ser188 by MPK38 kinase via direct interaction mediated by Cys152/Cys270 of STRAP and Cys339/Cys377 of MPK38 (redox-dependent). This phosphorylation modulates STRAP's pro-apoptotic function through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways. In vitro kinase assay, mutagenesis, Co-immunoprecipitation, inducible shRNA knockdown, adenoviral delivery in mice Cell Cycle High 25485581
2014 Mitochondrially-localized STRAP (TTC5) interacts with ATP synthase and downregulates mitochondrial ATP production. Under glucose-limiting conditions, mitochondrial STRAP sensitizes cancer cells to apoptosis, rescued by exogenous ATP. STRAP also augments the apoptotic effects of mitochondrial p53. Subcellular fractionation, co-immunoprecipitation, mitochondrial respiration assay, ATP measurement, apoptosis assay Cell Death and Differentiation High 25168243
2011 STRAP binds GSK3β through its WD40 domains and forms a ternary complex with GSK3β and Axin. STRAP also binds the intracellular fragment of Notch3 (ICN3) through its ankyrin repeat region and reduces ubiquitination of ICN3, stabilizing it. Co-immunoprecipitation, in vivo ubiquitination assay, GSK3β inhibitor experiments Cell Cycle Medium 21502811
2016 STRAP promotes β-catenin stability by binding GSK3β and reducing phosphorylation, ubiquitylation, and degradation of β-catenin through preventing its association with the destruction complex, thereby promoting Wnt/β-catenin signaling and CRC metastasis. Co-immunoprecipitation, ubiquitylation assay, in vitro and in vivo functional assays Oncotarget Medium 26910283
2017 STRAP competitively disrupts the association of PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly, leading to reduced H3K27me3 at NOTCH pathway gene promoters and epigenetic activation of NOTCH signaling to maintain cancer stem cell subpopulations in colorectal cancer. Co-immunoprecipitation, ChIP assay, shRNA knockdown, tumorsphere assays, in vivo xenograft Cancer Research Medium 28827371
2020 STRAP (TTC5) is a putative spliceosome-associated factor involved in the assembly of 17S U2 snRNP proteins. Upon Strap deletion in mouse embryoid bodies, numerous alternative splicing events occur, with STRAP preferentially targeting transcripts for nervous system development. In Xenopus, loss of Strap leads to impeded lineage differentiation, delayed neural tube closure, and altered exon skipping. eCLIP-seq, RNA-seq splicing analysis, deletion mouse model, Xenopus loss-of-function Nature Communications High 33230114
2016 STRAP acts as a scaffold protein in TLR2/4-mediated innate immune signaling by specifically binding TAK1 and IKKα along with NF-κB subunit p65, enhancing their association and facilitating p65 phosphorylation and nuclear translocation, resulting in enhanced pro-inflammatory cytokine production. At later times post-LPS stimulation, STRAP translocates to the nucleus and binds NF-κB to prolong IL-6 mRNA production. Co-immunoprecipitation, knockdown/overexpression, cytokine measurement, nuclear translocation assay Scientific Reports Medium 27934954
2017 STRAP acts as a positive scaffold regulator in TLR3-triggered signaling by strongly interacting with TBK1 and IRF3, enhancing IFN-β production. STRAP knockdown reduces pro-inflammatory cytokine and IFN levels, while overexpression increases them. The C-terminus of STRAP is essential for its functional activity. Co-immunoprecipitation, knockdown/overexpression, cytokine measurement Cellular Immunology Medium 28651742
2010 B-MYB directly interacts with STRAP (TTC5) via its N-terminal DNA-binding domain and amino acids 373-468, positively regulating STRAP activity. B-MYB enhances STRAP-mediated inhibition of TGF-β signaling and STRAP-mediated p53-induced apoptosis by modulating complex formation between TGF-β receptor and SMAD3/SMAD7 and promoting p53 nuclear translocation. Co-immunoprecipitation, reporter assays, confocal microscopy, apoptosis assays The Journal of Biological Chemistry Medium 21148321
2020 STRAP acetylation at lysines 147, 148, and 156 is mediated by the acetyltransferase CBP, and reversed by the deacetylase SIRT7. Hypo- or hyperacetylation mutations of STRAP at these sites influence p53 activation and stabilization. 5-FU treatment promotes STRAP mobilization from cytoplasm to nucleus and increases STRAP acetylation. In vitro acetylation assay, mutagenesis, subcellular fractionation, p53 activity assays International Journal of Molecular Sciences Medium 32527012
2011 STRAP regulates c-Jun stability by decreasing its ubiquitylation and proteasomal degradation; loss of STRAP accelerates c-Jun turnover and decreases cyclin D1 expression and cell growth without affecting JNK activity or c-Jun mRNA levels. Ubiquitylation assay, proteasome inhibitor experiments, mRNA and protein analysis, STRAP KO MEFs Biochemical and Biophysical Research Communications Medium 21397588
2014 STRAP downregulates E-cadherin and p21(Cip1) by abrogating binding of transcription factor Sp1 to its consensus binding sites, and recruits HDAC1 to Sp1 binding sites in the p21(Cip1) promoter. Loss of STRAP stabilizes Sp1 by repressing its ubiquitination in G1 phase. ChIP assay, co-immunoprecipitation, ubiquitination assay, STRAP KO and KD cell models Cell Cycle Medium 25483064
2013 TTC5 overexpression activates p53 pathway (up-regulating p53 and p21) and inhibits AP-1 transcriptional activity by significantly down-regulating expression, phosphorylation, and transcriptional activity of c-Jun, as well as expression and phosphorylation of the upstream kinase JNK/SAPK. Reporter assays, western blotting, overexpression experiments Molecular Biology Reports Low 24091941
2019 TTC5/STRAP acts as a negative autophagy regulator by binding to JMY (junction mediating and regulatory protein), antagonizing JMY's actin nucleation activity and its LC3-mediated recruitment to phagophore membranes. In vitro reconstitution showed that membrane-bound LC3 is sufficient to recruit JMY and stimulate JMY-mediated actin filament assembly, which TTC5/STRAP antagonizes. In vitro reconstitution, Co-immunoprecipitation, actin polymerization assay Autophagy Medium 30593260
2018 Csde1 (Cold shock domain protein e1/Unr) is the strongest Csde1-interacting protein in erythroblasts. Strap (TTC5) knockdown alters mRNA and/or protein expression of several Csde1-bound transcripts including Hmbs, eIF4g3, Pabpc4, Vim, and Elavl1, affecting translational regulation during hypoxia. Co-immunoprecipitation, RNA immunoprecipitation, shRNA knockdown, proteomics PloS One Medium 30138317
2025 The Csde1-Strap complex binds Bach2 mRNA to couple its decay with translation, restraining the magnitude and duration of Bach2 protein expression to regulate plasma cell differentiation. Absence of Csde1 or Strap de-couples Bach2 translation from mRNA decay, leading to elevated and prolonged Bach2 protein and impaired plasma cell differentiation. RNA interactome capture, CRISPR functional screening, RIP, RNA-seq, protein stability assays Nature Communications High 40133358
2008 p49/STRAP (TTC5) interacts with NDUFAB1 (a subunit of NADH dehydrogenase), co-localizing in the cell, and overexpression of p49/STRAP alters intracellular NAD levels, reduces the NAD/NADH ratio, and induces deacetylation of serum response factor. Yeast two-hybrid, co-localization, NAD/NADH measurement, co-immunoprecipitation BMC Cell Biology Low 18230186
2009 p49/STRAP (TTC5) interacts with the beta-sandwich domain of Hsp70, reduces Hsp40-stimulated ATPase activity of Hsp70, and inhibits the refolding activity of the Hsp70/Hsp40 chaperone system, qualifying it as a bona fide Hsp70 co-chaperone. Co-immunoprecipitation, ATPase assay, protein refolding assay Biochemical and Biophysical Research Communications Medium 19751705
2006 p49/STRAP (TTC5) specifically interacts with the N-terminus of GLUT4 (acidic motif Q7IGSEDG), co-localizes with GLUT4 and ER-resident calnexin in adipose cells, and overexpression of the GLUT4-binding domain of p49 reduces protein synthesis and cell-surface expression of GLUT4. Yeast two-hybrid, confocal immunofluorescence co-localization, overexpression functional assay Biochemical and Biophysical Research Communications Low 16647043
2025 STRAP is S-nitrosylated by iNOS specifically at Cys152 and Cys270 (the same residues required for ASK1 interaction), which disrupts the STRAP-ASK1 interaction, increases ASK1 activity, activates MKK3-p38 pathway, and enhances hydrogen peroxide-induced apoptosis. STRAP-C152/270S mutation constitutively activates the ASK1-MKK3-p38 pathway. S-nitrosylation assay, mutagenesis, Co-immunoprecipitation, kinase activity assay, apoptosis assay The Journal of Biological Chemistry High 41519199
2025 USP38 stabilizes STRAP via deubiquitination, thereby enhancing TGF-β/SMAD signaling and promoting atrial fibrosis in CKD-associated atrial fibrillation. STRAP knockdown reversed the pro-fibrotic effects induced by USP38 overexpression. Co-immunoprecipitation, ubiquitination assay, KO and TG mouse models, immunofluorescence Molecular Medicine Medium 40514673
2025 In C. elegans neurons, TTC5 (ttc-5) is required to recruit γ-tubulin to endosomal puncta (non-centrosomal MTOCs) for microtubule nucleation. Loss of ttc-5 reduces MT numbers similarly to γ-tubulin depletion and is essential for axon regeneration, where TTC5 directs γ-tubulin to the growth cone. C. elegans genetics, conditional single-cell degradation alleles, endogenous tagging, live imaging, axon regeneration assay bioRxivpreprint Medium 41279556
2025 Loss of TTC5-dependent tubulin autoregulation elevates soluble tubulin levels and induces microtubule hyperstability, disrupting cytoskeletal organization. This impairs localization of adhesion molecules at cell-cell junctions and extracellular matrix interfaces, compromising tissue architecture and reducing cell viability in human 3D cellular models. Human 3D cellular models, advanced optics, genetic perturbation, functional tissue assays bioRxivpreprint Medium bio_10.1101_2025.07.28.667019
2024 circPCNXL2 directly binds to STRAP and induces the interaction between STRAP and MEK1/2, resulting in activation of ERK/MAPK pathway and promoting ICC tumor growth and metastasis. RNA pulldown, mass spectrometry, RIP, Co-immunoprecipitation, functional cell and in vivo assays Molecular Cancer Medium 38365721

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Suspension trapping (STrap) sample preparation method for bottom-up proteomics analysis. Proteomics 342 24678027
2018 S-Trap, an Ultrafast Sample-Preparation Approach for Shotgun Proteomics. Journal of proteome research 266 30114372
2001 STRAP: editor for STRuctural Alignments of Proteins. Bioinformatics (Oxford, England) 191 11301311
2000 STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling. Molecular and cellular biology 148 10757800
2018 Comparison of In-Solution, FASP, and S-Trap Based Digestion Methods for Bottom-Up Proteomic Studies. Journal of proteome research 141 29754492
1998 Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling. The Journal of biological chemistry 104 9856985
2019 TTC5 mediates autoregulation of tubulin via mRNA degradation. Science (New York, N.Y.) 94 31727855
2019 Suspension Trapping (S-Trap) Is Compatible with Typical Protein Extraction Buffers and Detergents for Bottom-Up Proteomics. Journal of proteome research 86 30761899
2007 NM23-H1 tumor suppressor and its interacting partner STRAP activate p53 function. The Journal of biological chemistry 82 17916563
2017 STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway. Cancer research 75 28827371
2006 Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis. Cancer research 67 16778189
2023 Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials. The Lancet. Rheumatology 42 38251532
2018 Sanguinarine triggers intrinsic apoptosis to suppress colorectal cancer growth through disassociation between STRAP and MELK. BMC cancer 41 29783958
2013 Serine-threonine kinase receptor-associated protein (STRAP) regulates translation of type I collagen mRNAs. Molecular and cellular biology 40 23918805
2023 Squalene epoxidase promotes hepatocellular carcinoma development by activating STRAP transcription and TGF-β/SMAD signalling. British journal of pharmacology 36 36581319
2019 Self-Assembled STrap for Global Proteomics and Salivary Biomarker Discovery. Journal of proteome research 36 30848925
2004 DNA binding provides a molecular strap activating the adenovirus proteinase. Molecular & cellular proteomics : MCP 30 15220401
2016 Novel role of STRAP in progression and metastasis of colorectal cancer through Wnt/β-catenin signaling. Oncotarget 27 26910283
2011 TGF-beta-dependent and -independent roles of STRAP in cancer. Frontiers in bioscience (Landmark edition) 27 21196161
2011 Role of STRAP in regulating GSK3β function and Notch3 stabilization. Cell cycle (Georgetown, Tex.) 27 21502811
2004 STRAP is a strong predictive marker of adjuvant chemotherapy benefit in colorectal cancer. Neoplasia (New York, N.Y.) 27 15720808
2014 Investigation of in vitro anticancer and DNA strap interactions in live cells using carboplatin type Cu(II) and Zn(II) metalloinsertors. European journal of medicinal chemistry 26 25128669
2024 CircPCNXL2 promotes tumor growth and metastasis by interacting with STRAP to regulate ERK signaling in intrahepatic cholangiocarcinoma. Molecular cancer 24 38365721
2014 Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21(Cip1) by modulating the transcription factor Sp1. Cell cycle (Georgetown, Tex.) 23 25483064
2014 A crucial role for the phosphorylation of STRAP at Ser(188) by MPK38 in STRAP-dependent cell death through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways. Cell cycle (Georgetown, Tex.) 23 25485581
2015 Calix[4]pyrroles with Shortest Possible Strap: Exclusively Selective toward Fluoride Ion. Organic letters 18 26313641
2014 Overexpression of p49/STRAP alters cellular cytoskeletal structure and gross anatomy in mice. BMC cell biology 18 25183317
2008 Identification of a subunit of NADH-dehydrogenase as a p49/STRAP-binding protein. BMC cell biology 18 18230186
2008 ATM and Chk2 kinase target the p53 cofactor Strap. EMBO reports 18 18833288
2003 KISS for STRAP: user extensions for a protein alignment editor. Bioinformatics (Oxford, England) 18 14668241
2021 Carbaporphyrin Dimers That Bear a Rigid Naphthalene Motif as an Internal Strap. Organic letters 17 33577339
2020 STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells. Nature communications 17 33230114
2018 Dual Roles of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) in Redox-Sensitive Signaling Pathways Related to Cancer Development. Oxidative medicine and cellular longevity 17 29849900
2012 The p53 cofactor Strap exhibits an unexpected TPR motif and oligonucleotide-binding (OB)-fold structure. Proceedings of the National Academy of Sciences of the United States of America 17 22362889
2015 C-STrap Sample Preparation Method--In-Situ Cysteinyl Peptide Capture for Bottom-Up Proteomics Analysis in the STrap Format. PloS one 16 26407052
2009 Developmental morphology of strap-shaped gametophytes of Colysis decurrens: a new look at meristem development and function in fern gametophytes. Annals of botany 15 19812067
2020 STRAP and NME1 Mediate the Neurite Growth-Promoting Effects of the Neurotrophic Factor GDF5. iScience 14 32853992
2019 TRIP13 interference inhibits the proliferation and metastasis of thyroid cancer cells through regulating TTC5/p53 pathway and epithelial-mesenchymal transition related genes expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 31648166
2010 B-MYB positively regulates serine-threonine kinase receptor-associated protein (STRAP) activity through direct interaction. The Journal of biological chemistry 14 21148321
2009 Serine threonine receptor-associated protein (STRAP) plays a role in the maintenance of mesenchymal morphology. Cellular signalling 14 19781628
2021 Comparison of protein characterization using In solution and S-Trap digestion methods for proteomics. Biochemical and biophysical research communications 13 34922203
2020 SIRT7 Deacetylates STRAP to Regulate p53 Activity and Stability. International journal of molecular sciences 13 32527012
2016 Does p49/STRAP, a SRF-binding protein (SRFBP1), modulate cardiac mitochondrial function in aging? Experimental gerontology 13 27337995
2014 Cofactor Strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase. Cell death and differentiation 13 25168243
2005 Structural interpretation of mutations and SNPs using STRAP-NT. Protein science : a publication of the Protein Society 13 16322575
2013 TTC5 is required to prevent apoptosis of acute myeloid leukemia stem cells. Cell death & disease 12 23559008
2023 Suspension TRAPping Filter (sTRAP) Sample Preparation for Quantitative Proteomics in the Low µg Input Range Using a Plasmid DNA Micro-Spin Column: Analysis of the Hippocampus from the 5xFAD Alzheimer's Disease Mouse Model. Cells 11 37174641
2018 Strap associates with Csde1 and affects expression of select Csde1-bound transcripts. PloS one 11 30138317
2018 Oncogenic roles of serine-threonine kinase receptor-associated protein (STRAP) in osteosarcoma. Cancer chemotherapy and pharmacology 11 30276452
2021 Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines. Cancers 10 34206917
2021 Folding in Place: Design of β-Strap Motifs to Stabilize the Folding of Hairpins with Long Loops. The Journal of organic chemistry 10 34499510
2019 Regulation of JMY's actin nucleation activity by TTC5/STRAP and LC3 during autophagy. Autophagy 10 30593260
2018 Oncogenic STRAP Supports Hepatocellular Carcinoma Growth by Enhancing Wnt/β-Catenin Signaling. Molecular cancer research : MCR 10 30257989
2016 STRAP Acts as a Scaffolding Protein in Controlling the TLR2/4 Signaling Pathway. Scientific reports 10 27934954
2020 S-Trap Eliminates Cell Culture Media Polymeric Surfactants for Effective Proteomic Analysis of Mammalian Cell Bioreactor Supernatants. Journal of proteome research 9 32207952
2020 Developing a mass spectrometry-based assay for the ovarian cancer biomarker CA125 (MUC16) using suspension trapping (STrap). Analytical and bioanalytical chemistry 9 32215689
2017 STRAP positively regulates TLR3-triggered signaling pathway. Cellular immunology 9 28651742
2011 STRAP regulates c-Jun ubiquitin-mediated proteolysis and cellular proliferation. Biochemical and biophysical research communications 9 21397588
2025 Deep molecular profiling of synovial biopsies in the STRAP trial identifies signatures predictive of treatment response to biologic therapies in rheumatoid arthritis. Nature communications 8 40603860
2024 Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay. Nature communications 8 39551769
2022 TTC5 syndrome: Clinical and molecular spectrum of a severe and recognizable condition. American journal of medical genetics. Part A 8 35670379
2013 STRAP PTM: Software Tool for Rapid Annotation and Differential Comparison of Protein Post-Translational Modifications. Current protocols in bioinformatics 8 25422678
1999 Influence of girth strap tensions on athletic performance of racehorses. Equine veterinary journal. Supplement 8 10659222
2023 Comparison of SPEED, S-Trap, and In-Solution-Based Sample Preparation Methods for Mass Spectrometry in Kidney Tissue and Plasma. International journal of molecular sciences 7 37047281
2017 Downregulation of STRAP promotes tumor growth and metastasis in hepatocellular carcinoma via reducing PTEN level. IUBMB life 7 29283497
2006 HotSwap for bioinformatics: a STRAP tutorial. BMC bioinformatics 7 16469097
2008 Strap: a versatile transcription co-factor. Cell cycle (Georgetown, Tex.) 6 18719389
2006 Identification and characterization of p49/STRAP as a novel GLUT4-binding protein. Biochemical and biophysical research communications 6 16647043
2025 Ubiquitin-specific protease 38 modulates atrial fibrillation susceptibility in chronic kidney disease via STRAP stabilization and activation of TGF-β/SMAD signaling. Molecular medicine (Cambridge, Mass.) 5 40514673
2022 Serine-Threonine Kinase Receptor Associate Protein (STRAP) confers an aggressive phenotype in neuroblastoma via regulation of Focal Adhesion Kinase (FAK). Journal of pediatric surgery 5 35272839
2020 Bi-allelic TTC5 variants cause delayed developmental milestones and intellectual disability. Journal of medical genetics 5 32439809
2016 X-radiation enhances the collagen type I strap formation and migration potentials of colon cancer cells. Oncotarget 5 27655687
2015 Keratinized strap cells: a rare cytological atypia resembles Anitschkow cells, in human oral neoplasm. International journal of clinical oncology 5 26160758
2013 Human TTC5, a novel tetratricopeptide repeat domain containing gene, activates p53 and inhibits AP-1 pathway. Molecular biology reports 5 24091941
2021 Characterizing the Host Coral Proteome of Platygyra carnosa Using Suspension Trapping (S-Trap). Journal of proteome research 4 33630606
2021 A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies. Journal of human genetics 4 34168248
2021 Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer. International journal of molecular sciences 4 34947995
2017 p49/STRAP, a Serum Response Factor Binding Protein (SRFBP1), Is Involved in the Redistribution of Cytoskeletal F-Actin Proteins during Glucose Deprivation. The journal of nutrition, health & aging 4 29188873
2009 Interaction of Hsp70 with p49/STRAP, a serum response factor binding protein. Biochemical and biophysical research communications 4 19751705
2024 Protocol for feeding strategy and proteomics analysis of zebrafish Danio rerio using S-trap and iTRAQ techniques. STAR protocols 3 39661508
2023 "Out of the blue": A qualitative study exploring the experiences of women and next of kin receiving unexpected results from BRA-STRAP research gene panel testing. Journal of genetic counseling 3 37864663
2020 STRAP reduces endoplasmic reticulum stress and apoptosis in cardiomyocytes and attenuates myocardial ischemia-reperfusion injury by activating PI3K/PDK1/Akt signaling pathway. European review for medical and pharmacological sciences 3 32373981
2013 Padded self-adhesive strap immobilization following newborn bladder exstrophy closure: the Utah straps. The Journal of urology 3 23810641
2025 A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay. Nature communications 2 40133358
2022 Ultrasound-targeted microbubble destruction (UTMD)-mediated miR-150-5p attenuates oxygen and glucose deprivation-induced cardiomyocyte injury by inhibiting TTC5 expression. Molecular biology reports 2 35357625
2024 STRAP upregulates antiviral innate immunity against PRV by targeting TBK1. Virology journal 1 39182136
2024 STRAP Knockdown Inhibits Migration and Growth of Non-Small Cell Lung Cancer. Bulletin of experimental biology and medicine 1 39455498
2026 S-nitrosylation of the scaffold protein STRAP enhances oxidative stress-induced apoptosis. The Journal of biological chemistry 0 41519199
2025 The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer. Cells 0 40558481
2025 Tubulin autoregulation factors SCAPER and TTC5 recruit γ-tubulin to non-centrosomal MTOCs for neuronal microtubule nucleation and axon regeneration. bioRxiv : the preprint server for biology 0 41279556
2012 StRAP: an integrated resource for profiling high-throughput cancer genomic data from stress response studies. PloS one 0 23284744