Affinage

TACC2

Transforming acidic coiled-coil-containing protein 2 · UniProt O95359

Length
2948 aa
Mass
309.4 kDa
Annotated
2026-06-10
17 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TACC2 is a centrosome- and microtubule-associated protein that functions both in mitotic spindle regulation and as a cytoplasmic anchor controlling chromatin-modifying complexes, positioning it as a context-dependent tumor suppressor (PMID:10749935, PMID:39793578). At the cytoskeleton, TACC2 acts as a microtubule plus-end-tracking protein whose C-terminal TACC domain is necessary and sufficient for plus-end localization and promotion of microtubule polymerization, while its N-terminal region acts dominant-negatively (PMID:27559128); it normally stabilizes mitotic microtubules, an activity that opposes the spindle disruption caused by SV40 large T antigen binding (PMID:19671663). TACC2 is phosphorylated during mitosis by TTK/Mps1 kinase, which is required to maintain its centrosomal localization and proper chromosome alignment and centrosome separation (PMID:15304323). A central regulatory function is the cytoplasmic sequestration of NuRD and CoREST co-repressor components (MTA1, MBD3, HMG20B); loss of TACC2 permits their nuclear translocation, driving epigenetic repression of CDKN1A and of CCL3/CCL4 chemokines, thereby elevating CDK activity and suppressing CD8+ T cell infiltration (PMID:39793578, PMID:40442694). TACC2 expression is itself transcriptionally controlled, being directly induced by androgen receptor in prostate cancer cells (PMID:22456197) and repressed by SUV39H1-mediated H3K9 trimethylation during fibroblast-to-myofibroblast transition (PMID:41861065). TACC2 also physically associates with GAS41 and the SWI/SNF chromatin remodeling complex (PMID:12620397). Notably, TACC2 is dispensable for normal mouse development, proliferation, and centrosome homeostasis (PMID:15226440).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 Medium

    Established that TACC2 (AZU-1) is a cytoplasmic protein with tumor-suppressive function, framing it as more than a passive structural component.

    Evidence Subcellular fractionation and viral reexpression in mammary epithelial T4-2 cells with 3D culture and xenograft phenotypes

    PMID:10749935

    Open questions at the time
    • Molecular mechanism of malignancy suppression not defined
    • No interaction partners identified at this stage
  2. 2003 Medium

    Linked TACC2 to gene regulation by identifying physical association with the SWI/SNF chromatin remodeling machinery, suggesting a role beyond the cytoskeleton.

    Evidence Co-immunoprecipitation/pulldown identifying GAS41 and SWI/SNF components

    PMID:12620397

    Open questions at the time
    • Functional consequence of SWI/SNF binding not tested
    • Single lab, no reciprocal validation reported
  3. 2004 Medium

    Defined how TACC2 is positioned at the centrosome during mitosis, showing TTK kinase phosphorylation is required for its centrosomal retention and accurate chromosome segregation.

    Evidence Pulldown with wild-type vs kinase-dead TTK, siRNA depletion, and immunofluorescence

    PMID:15304323

    Open questions at the time
    • Phosphosite(s) on TACC2 not mapped
    • Direct vs indirect phosphorylation not fully resolved
  4. 2004 High

    Tested the in vivo requirement for TACC2 and found it dispensable for normal proliferation, centrosome homeostasis, and tumor suppression in mice, complicating a simple essential mitotic role.

    Evidence TACC2 knockout mouse, proliferation and cell cycle assays, centrosome counting

    PMID:15226440

    Open questions at the time
    • Functional redundancy with TACC paralogs not directly addressed
    • Context-specific phenotypes not explored
  5. 2009 Medium

    Demonstrated TACC2 directly stabilizes mitotic microtubules by showing it counteracts SV40 large T antigen-induced spindle dysfunction.

    Evidence Co-IP/direct binding, T-antigen deletion mutants, immunofluorescence, TACC2 overexpression rescue

    PMID:19671663

    Open questions at the time
    • Endogenous microtubule-stabilizing mechanism not isolated from viral context
    • Single lab
  6. 2016 High

    Assigned a precise molecular activity by showing TACC2 is a microtubule plus-end-tracking protein whose C-terminal TACC domain drives polymerization, with cell-type-dependent effects.

    Evidence Live imaging of GFP-TACC2 in Xenopus cells, structure-function deletions, MT polymerization measurements

    PMID:27559128

    Open questions at the time
    • Why activity differs between mesenchymal and neuronal cells unexplained
    • Human protein not directly assayed in this study
  7. 2012 High

    Placed TACC2 within hormonal signaling by establishing it as a direct AR target gene driving cell cycle progression in castration-resistant prostate cancer.

    Evidence ChIP-cloning, ChIP for histone marks, AR knockdown, bicalutamide, siRNA, overexpression, xenograft

    PMID:22456197

    Open questions at the time
    • Cytoskeletal vs chromatin role in this growth phenotype not separated
    • Downstream effectors of TACC2-driven proliferation unresolved
  8. 2025 High

    Revealed the central tumor-suppressive mechanism: cytoplasmic TACC2 sequesters NuRD/CoREST co-repressors, and its loss permits nuclear translocation that epigenetically silences CDKN1A and elevates CDK activity.

    Evidence Reciprocal Co-IP, ChIP, TACC2 knockout mouse, ESCC organoids, fractionation, siRNA + CDK inhibitor in vivo

    PMID:39793578

    Open questions at the time
    • Structural basis of cytoplasmic anchoring not defined
    • How TACC2 microtubule activity relates to co-repressor sequestration unclear
  9. 2025 Medium

    Extended the co-repressor sequestration model to immune evasion, showing TACC2 loss derepresses CCL3/CCL4 and reduces CD8+ T cell infiltration, with therapeutic relevance to checkpoint blockade.

    Evidence ChIP, Co-IP, TACC2 overexpression mouse models, anti-PD-1 combination in vivo

    PMID:40442694

    Open questions at the time
    • Direct demonstration that chemokine repression alone drives T cell exclusion incomplete
    • Generality across tumor types not established
  10. 2025 Medium

    Identified an oncogenic gain-of-function for a PLEKHA1-TACC2 fusion acting through EphA2/AKT/MMP2 signaling and vascular mimicry, distinct from wild-type TACC2 function.

    Evidence RNA-seq fusion identification, vascular mimicry assays, ubiquitylation assay, Trp53-deletion transgenic mouse, EphA2 inhibitor in vivo

    PMID:40615663

    Open questions at the time
    • Contribution of the TACC2 portion vs PLEKHA1 portion not dissected
    • Relationship to native TACC2 activity unclear
  11. 2026 High

    Defined upstream epigenetic control of TACC2, showing SUV39H1-mediated H3K9me3 represses its promoter to license fibroblast-to-myofibroblast transition in cardiac fibrosis.

    Evidence CUT&Tag-seq, RNA-seq, gain/loss of function epistasis, two conditional KO mouse models, transverse aortic constriction

    PMID:41861065

    Open questions at the time
    • Whether co-repressor sequestration underlies the fibrosis phenotype not tested
    • Mechanism linking TACC2 level to myofibroblast program unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TACC2's microtubule plus-end-tracking activity is mechanistically integrated with its cytoplasmic sequestration of NuRD/CoREST co-repressors remains unresolved.
  • No unified structural model linking cytoskeletal and chromatin functions
  • Determinants of cytoplasmic vs centrosomal partitioning unknown
  • Paralog redundancy with TACC1/TACC3 not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2 R-HSA-168256 Immune System 1

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 AZU-1 (TACC2) protein resides predominantly in a detergent-extractable cytoplasmic pool in mammary epithelial cells; reexpression of AZU-1 in tumorigenic T4-2 cells was sufficient to reduce their malignant phenotype both in culture and in vivo, establishing a functional tumor-suppressive role in breast morphogenesis. Subcellular fractionation, viral vector-mediated reexpression, 3D culture and xenograft assays Molecular biology of the cell Medium 10749935
2003 TACC2 physically interacts with GAS41 and components of the SWI/SNF chromatin remodeling complex, suggesting a role in gene regulation via chromatin remodeling. Co-immunoprecipitation / pulldown assays Genomics Medium 12620397
2004 TACC2 is phosphorylated during mitosis by the TTK kinase signaling pathway; TTK kinase activity is required for centrosomal localization of TACC2, as expression of a kinase-dead TTK mutant or TTK depletion displaces TACC2 from the centrosome (but not other centrosomal proteins such as γ-tubulin and NuMA), leading to chromosome misalignment/lagging and reduced centrosome separation. Pulldown of TACC2 by wild-type vs kinase-dead TTK, immunofluorescence, TTK depletion by siRNA FEBS letters Medium 15304323
2004 In TACC2-deficient mouse embryonic fibroblasts, proliferation, cell cycle progression, and centrosome numbers are comparable to wild-type cells, indicating TACC2 is dispensable for normal mouse cell proliferation and centrosome homeostasis, and TACC2 knockout mice develop normally without increased tumor incidence. TACC2 knockout mouse model, cell proliferation assays, cell cycle analysis, centrosome counting Molecular and cellular biology High 15226440
2009 SV40 large T antigen directly binds TACC2 protein; this interaction induces microtubule dysfunction, disorganized mitotic spindles, slow mitotic progression, and chromosome missegregation. Overexpression of TACC2 suppresses T-antigen-induced microtubule destabilization, demonstrating that TACC2 normally stabilizes microtubules in mitosis. Co-immunoprecipitation/direct binding assay, N-terminal deletion mutants of T antigen, immunofluorescence microscopy, TACC2 overexpression rescue Journal of cell science Medium 19671663
2012 TACC2 is a direct androgen receptor (AR)-regulated gene; a functional AR-binding site containing two canonical androgen response elements was identified near the TACC2 gene with active histone modification marks. AR knockdown or bicalutamide treatment abolished androgen-dependent TACC2 induction. TACC2 siRNA knockdown reduced cell growth and cell cycle progression in castration-resistant prostate cancer (CRPC) cell models, while TACC2 overexpression accelerated the cell cycle. ChIP-cloning, ChIP for histone marks, AR knockdown, pharmacological inhibition (bicalutamide), siRNA knockdown, cell cycle analysis, overexpression, castrated mouse xenograft model Molecular endocrinology (Baltimore, Md.) High 22456197
2016 Xenopus TACC2 localizes to microtubule plus ends in front of EB1 and overlapping with TACC1/TACC3, functioning as a +TIP. The C-terminal region (containing the TACC domain) is both necessary and sufficient for plus-end localization and promotion of MT polymerization, while the N-terminal region cannot bind MT plus ends but acts in a dominant-negative manner to reduce polymerization rates. TACC2 promotes MT polymerization in mesenchymal cells but not neuronal growth cones. Live imaging of GFP-tagged TACC2 in Xenopus embryonic cells, structure-function analysis with N-terminal and C-terminal deletion constructs, MT polymerization rate measurements Molecular biology of the cell High 27559128
2025 TACC2 interacts with components of the NuRD and CoREST co-repressor complexes (MTA1, MBD3, HMG20B) in the cytoplasm. Loss of TACC2 causes nuclear translocation of these co-repressor proteins, leading to functional NuRD/CoREST complex assembly in the nucleus, epigenetic repression of CDKN1A (p21), elevated CDK1/2 activation, and increased sensitivity to CDK inhibitors. Co-immunoprecipitation, ChIP, TACC2 knockout mouse model, ESCC organoids, subcellular fractionation, siRNA + CDK inhibitor combination treatment in vivo Med (New York, N.Y.) High 39793578
2025 TACC2 interacts with the NuRD/CoREST complex and inhibits its nuclear translocation; in soft tissue sarcoma, TACC2 loss permits nuclear NuRD/CoREST translocation which represses CCL3 and CCL4 chemokine transcription, thereby reducing CD8+ T cell infiltration. TACC2 overexpression synergizes with anti-PD-1 therapy in vivo. ChIP, co-immunoprecipitation, TACC2 overexpression mouse models, anti-PD-1 combination treatment in vivo Molecular cancer Medium 40442694
2025 The PLEKHA1-TACC2 fusion protein activates the EphA2/AKT/MMP2 signaling pathway and promotes vascular mimicry formation by reducing EphA2 ubiquitylation, with oncogenic activity demonstrated in transgenic ESCC mouse models. RNA sequencing for fusion identification, functional assays for vascular mimicry, ubiquitylation assay, transgenic mouse model with Trp53 deletion, EphA2 inhibitor treatment in vivo Cell death and differentiation Medium 40615663
2026 SUV39H1 (Suv39h1) directly binds the TACC2 promoter and represses TACC2 transcription by catalyzing H3K9 trimethylation during fibroblast-to-myofibroblast transition. TACC2 depletion normalized the transition despite SUV39H1 deficiency, while TACC2 overexpression suppressed the transition, placing TACC2 downstream of SUV39H1 in cardiac fibrosis regulation. CUT&Tag-seq, RNA-seq, TACC2 depletion and overexpression, cardiac fibroblast-specific conditional knockout mouse models (Col1a2-CreERT and PostnMCM), transverse aortic constriction heart failure model Cardiovascular research High 41861065

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression. Molecular biology of the cell 77 10749935
2012 TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer. Molecular endocrinology (Baltimore, Md.) 41 22456197
2003 Molecular cloning, genomic structure and interactions of the putative breast tumor suppressor TACC2. Genomics 37 12620397
2004 The centrosomal, putative tumor suppressor protein TACC2 is dispensable for normal development, and deficiency does not lead to cancer. Molecular and cellular biology 32 15226440
2004 TTK kinase is essential for the centrosomal localization of TACC2. FEBS letters 24 15304323
2021 Stage 4 pancreatic adenocarcinoma harbouring an FGFR2-TACC2 fusion mutation with complete response to erdafitinib a pan-fibroblastic growth factor receptor inhibitor. BMJ case reports 19 34511423
2001 Cloning and structural characterization of ECTACC, a new member of the transforming acidic coiled coil (TACC) gene family: cDNA sequence and expression analysis in human microvascular endothelial cells. Cytokine 18 11161455
2016 Xenopus TACC2 is a microtubule plus end-tracking protein that can promote microtubule polymerization during embryonic development. Molecular biology of the cell 13 27559128
2022 FGFR2::TACC2 fusion as a novel KIT-independent mechanism of targeted therapy failure in a multidrug-resistant gastrointestinal stromal tumor. Genes, chromosomes & cancer 12 35170141
2009 Simian virus 40 large T antigen targets the microtubule-stabilizing protein TACC2. Journal of cell science 11 19671663
2020 Histology-specific FGFR2 alterations and FGFR2-TACC2 fusion in mixed adenoid cystic and neuroendocrine small cell carcinoma of the uterine cervix. Gynecologic oncology reports 8 33241100
2025 Loss of TACC2 impairs chemokine CCL3 and CCL4 expression and reduces response to anti-PD-1 therapy in soft tissue sarcoma. Molecular cancer 7 40442694
2014 Expression pattern of an evolutionarily conserved splice variant in the rat Tacc2 gene. Genesis (New York, N.Y. : 2000) 7 24700488
2025 Inactivation of TACC2 epigenetically represses CDKN1A and confers sensitivity to CDK inhibitors. Med (New York, N.Y.) 4 39793578
2021 Nanopore sequencing reveals TACC2 locus complexity and diversity of isoforms transcribed from an intronic promoter. Scientific reports 3 33931666
2026 Suppressor of variegation 3-9 homolog 1 deficiency attenuates cardiac fibrosis and rescues heart failure through TACC2. Cardiovascular research 0 41861065
2025 The PLEKHA1-TACC2 fusion gene drives tumorigenesis via vascular mimicry formation in esophageal squamous-cell carcinoma. Cell death and differentiation 0 40615663

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