TACC3 (transforming, acidic coiled-coil containing protein 3)

2009-04-01   Melissa R Eslinger , Brenda Lauffart , Ivan H Still 


Atlas Image


Atlas Image


The gene is composed of 16 verified exons spanning 23.6kb.


Encodes a single confirmed 2788nt transcript (NM_006342) (Still et al., 1999), although one additional transcript with two additional small 5 coding exons between exon 1 and the first coding exon (exon 2), based on NM_006342, is indicated based on several cDNAs that may however be from suspect cDNA libraries (see UCSC Genome Bioinformatics Site (http://genome.ucsc.edu)). Four additional transcripts variants are suggested based on singleton Expressed sequence tags in tumor cell lines (AW516785, BE552327, BX331864) and/or stem cell progenitors (AV761182, CX872433).




Atlas Image


TACC3 encodes a single protein of 838 amino acids with a molecular mass of 90kDa (Still et al., 1999). The protein is heavily phosphorylated based on direct evidence and based on predictions from the Xenopus and mouse orthologs (Beausoleil et al., 2004; Beausoleil et al., 2008; Kinoshita et al., 2005; Yu et al., 2007; Cantin et al., 2008; Dephoure et al., 2008). Thus, human TACC3 migrates at approximately 150kDa in SDS-PAGE. Additional variants are suggested based on singleton cDNAs (see above) but their predicted protein isoforms have not been confirmed.


High levels during early (mouse) embryogenesis, in particular during early differentiation of specific tissues (Sadek et al., 2003). In adult tissues, expression is relatively limited, with high levels noted in hematological tissues such as the thymus, spleen and leukocytes, and reproductive tissues, especially meiotic cells of the testes and ovary (Still et al., 1999; Sadek et al., 2003). Epithelial layers of the lung, mammary gland and ovary express TACC3 and alterations in expression are noted during tumorigenesis (see below). Expression in human adult tissues is summarized in Lauffart et al. 2006.


Human (and mouse) TACC3 is located in the interphase nucleus and/or cytosol, depending on cell type and cancer type (Gergely et al., 2000; Aitola et al., 2003; Lauffart et al., 2005; Jung et al., 2006; Vettaikkorumakankauv et al., 2008). TACC3 does not however contain a classical nuclear localisation signal (Still et al., 1999). TACC3 associates with the centrosome in a cell cycle dependent manner (Gergely et al., 2000). Phosphorylation of TACC3 by Aurora A on key serine residues is required for this interaction (Kinoshita et al., 2005; LeRoy et al., 2007). Overexpression of TACC3 from artificial constructs can result in accumulation in the cytosol of some cells resulting in oligmerisation in punctate structures (Gergely et al., 2000).


Gene knockout and knockdown studies in mouse have indicated that TACC3 is vital for embryonic development. A functionally null TACC3 mutant dies during mid to late gestation due to excessive apoptosis affecting hematopoietic and other organ systems (Piekorz et al., 2002). Hypomorphic alleles result in defects in mitosis affecting mesenchymal sclerotome and therefore the axial skeleton (Yao et al., 2007). These mutational mouse models indicate that TACC3 has a role in chromosomal alignment, separation and cytokinesis and that TACC3 can be associated with p53-mediated apoptosis.
TACC3 has a well characterized function in microtubule dynamics, particularly during mitosis, based on mutational analysis (see above) and physical interactions with Aurora A and Aurora B kinases, CKAP5 (ch-TOG/XMAP215) and AKAP9 via the TACC domain (see Peset and Vernos, 2008 for review). Interaction with CEP120 is important in interkinetic nuclear migration and maintenance of neural progenitor self-renewal during the development of the neocortex (Xie et al., 2007). Phosphorylation of Ser34, Ser552 and Ser558 by Aurora A are required for localization to centrosomes and is necessary for recruitment of CKAP5 and nucleation of microtubules (Kinoshita et al., 2005; LeRoy et al., 2007). Ser25, Thr59, Ser71, Ser317, and Ser 434 are presumed targets for cyclin dependent kinases in mitotic HeLa cells (Yu et al., 2007; Cantin et al., 2008; Dephoure et al., 2008). By homology, Ser558 phosphorylation by TPX2 is required for nucleation of microtubules in meiotic oocytes (Brunet et al., 2008).
TACC3 also has a defined role in interphase cells as a transcriptional cofactor for the aryl-nuclear translocator protein (Sadek, 2000), FOG1 (Garriga-Canut and Orkin, 2004; Simpson et al., 2004) and is a possible indirect activator of CREB via FHL family of coactivator/corepressor proteins (Lauffart et al., 2007b). Roles in transcriptional regulation have also been proposed based on TACC3 binding to GAS41 (YEATS4) via the SDP repeat, histone acetyl transferases hGCN5L2 (KAT2A), pCAF (KAT2B), and retinoid X-receptor beta via the TACC domain (Gangisetty, 2004; Lauffart et al., 2002; Vettaikkorumakankauv et al., 2008). TACC3 functionally interacts with MBD2 bound to methylated promoters, promoting transcription by displacement of HDAC2 and recruitment of KAT2B (Angrisano et al., 2006). Human TACC3 may be involved in transcriptional termination and/or pre-mRNA splicing through TTF2 (Leonard et al., 2003). TACC3 can interact with BARD1, BRCA1 and p53 and has been shown to have some protective affects against adriamycin-mediated DNA damage in ovarian cancer cells (Lauffart et al., 2007a). Phosphorylation of the last amino acid of the SDP repeat, Ser434, is noted in nuclear extracts of HeLa (Beausoleil, 2004; Beausoleil, 2006), although its functional significance is unknown.


Member of the TACC family, based on the presence of the evolutionarily conserved approximately 200 amino acid carboxy terminal coiled coil domain (TACC domain) (Still et al., 1999; Still et al., 2004). TACC3 orthologues are noted in all vertebrates sequenced to date (Still et al., 2004 and Still unpublished). However, the central region between the conserved N-terminal region and the TACC domain is highly variable in size and sequence. The SDP repeats are noted within the central region in most vertebrates except mouse and rat (Still et al., 2004).



Somatic mutations noted in ovarian cancer samples (Lauffart et al., 2005; Eslinger, 2006).
Atlas Image
See legend for normal protein.

Implicated in

Entity name
Ovarian cancer
Overexpression of TACC3 is associated with chemoresistance in ovarian tumors (LEsperance et al., 2006).
Total cellular expression or nuclear localization lost in ovarian cancer (Lauffart et al., 2005).
Entity name
Non-small cell lung cancer
High TACC3 expression is an independent prognostic indicator associated with significantly shorter median survival time. TACC3 expression was correlated with p53 expression and poor prognosis (Jung et al., 2006).
A high level of TACC3 expression was observed in 14.8% of cases of non small cell lung cancer, predominantly of the squamous cell carcinoma type (Jung et al., 2006).
Entity name
Breast cancer
Loss of TACC3 is observed as a predictor of poor prognosis in breast cancer (Conte et al., 2002).
TACC3 protein downregulated in breast cancer (Conte et al., 2002).
Entity name
TACC3 overexpression correlates with the t(4;14) translocation that is associated with poor prognosis (Stewart et al., 2004).
TACC3 is located close to the MMSET gene that is rearranged in t(4;14) translocation (Still et al., 1999). This rearrangement upregulates the TACC3 gene (Stewart et al., 2004).
Entity name
Thyroid cancer
Reduction of expression associated with increased malignancy in cell line models (Ulisse et al., 2007).
Analysis of differentiated thyroid cancers indicates that TACC3 mRNA levels were either upregulated (44%) or downregulated (56%) in tumors, in some cases correlation was observed between TACC3 and Aurora-A kinase (Ulisse et al., 2007). However protein analysis was not reported.



Rearrangements of the human TACC3 gene have not been described. However, translocation breakpoints in the WHSC1 gene, associated with multiple myeloma upregulate the intact TACC3 promoter (Stewart et al., 2004). Tacc3 in the mouse genome is a site of proviral integration of MoMuLV transmitted via milk from infected mothers. This leads to upregulation of the gene and leads to the development of lymphomas (Chakraborty et al., 2008).


Pubmed IDLast YearTitleAuthors
126426242003Aint/Tacc3 is highly expressed in proliferating mouse tissues during development, spermatogenesis, and oogenesis.Aitola M et al
164106162006TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters.Angrisano T et al
169642432006A probability-based approach for high-throughput protein phosphorylation analysis and site localization.Beausoleil SA et al
188333362008Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes.Brunet S et al
182203362008Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.Cantin GT et al
185019452008Retroviral gene insertion in breast milk mediated lymphomagenesis.Chakraborty J et al
186696482008A quantitative atlas of mitotic phosphorylation.Dephoure N et al
147674762004The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases.Gangisetty O et al
150376322004Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hematopoiesis.Garriga-Canut M et al
111210382000The TACC domain identifies a family of centrosomal proteins that can interact with microtubules.Gergely F et al
157058732005Protein expression profiling identifies subclasses of breast cancer and predicts prognosis.Jacquemier J et al
169303302006Expression of transforming acidic coiled-coil containing protein 3 is a novel independent prognostic marker in non-small cell lung cancer.Jung CK et al
161722052005Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis.Kinoshita K et al
167731802006Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors.L'Espérance S et al
184812062007Interaction of TACC proteins with the FHL family: implications for ERK signaling.Lauffart B et al
175456172007Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora A activity.LeRoy PJ et al
129277882003hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing.Leonard D et al
186563602008The TACC proteins: TACC-ling microtubule dynamics and centrosome function.Peset I et al
118471132002The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis.Piekorz RP et al
110252032000Isolation and characterization of AINT: a novel ARNT interacting protein expressed during murine embryonic development.Sadek CM et al
127115502003TACC3 expression is tightly regulated during early differentiation.Sadek CM et al
152349872004A classic zinc finger from friend of GATA mediates an interaction with the coiled-coil of transforming acidic coiled-coil 3.Simpson RJ et al
151987342004Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma.Stewart JP et al
152070082004Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms.Still IH et al
103664481999The third member of the transforming acidic coiled coil-containing gene family, TACC3, maps in 4p16, close to translocation breakpoints in multiple myeloma, and is upregulated in various cancer cell lines.Still IH et al
179141112007Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues.Ulisse S et al
179200172007Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool.Xie Z et al
173593032007TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton.Yao R et al
179246792007Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.Yu LR et al

Other Information

Locus ID:

NCBI: 10460
MIM: 605303
HGNC: 11524
Ensembl: ENSG00000013810


dbSNP: 10460
ClinVar: 10460
TCGA: ENSG00000013810


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
RNA transportKEGGko03013
RNA transportKEGGhsa03013

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
228373872012Transforming fusions of FGFR and TACC genes in human glioblastoma.255
231754432013Oncogenic FGFR3 gene fusions in bladder cancer.129
232988362013The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma.83
212975822011A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging.64
203489562010A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.63
211134142010Integrated genomic analyses identify ERRFI1 and TACC3 as glioblastoma-targeted genes.47
205666842010Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability.41
233486902013TACC3 promotes epithelial-mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways.41
209238382010Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment.37
252949082014Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma.37


Melissa R Eslinger ; Brenda Lauffart ; Ivan H Still

TACC3 (transforming, acidic coiled-coil containing protein 3)

Atlas Genet Cytogenet Oncol Haematol. 2009-04-01

Online version: http://atlasgeneticsoncology.org/gene/42458/tacc3