TACC2 (transforming, acidic coiled-coil containing protein 2)

2013-08-01   Ivan H Still , Brenda Lauffart 

1 Department of Biological Sciences, Arkansas Tech University, 1701 N Boulder Ave Russellville, AR 72801, USA (IHS); Department of Physical Sciences Arkansas Tech University, 1701 N Boulder Ave Russellville, AR 72801, USA (BL)


Atlas Image


Atlas Image


The gene is composed of 28 exons spanning 265369 bp.


Transcripts depicted above encompass most transcripts evident in AceView and USGC genome browsers. Most other AceView "transcripts" appear to be subsets of those shown or unspliced. AF176646 represents the published "Azu-1" variant (Chen et al., 2000); although no other cDNAs support the 5 end as a transcriptional start site (123886229 bp), a H3K27 acetylation cluster is noted in this region (ENCODE Project Consortium, 2011). AF220152 represents the "ECTACC variant" (Pu et al., 2001), first 13 bases of which do not match the genomic DNA and no other cDNAs support its 5 end as a transcriptional start site. Transcription start site at 123754142 bp identified in a global search for alternative promoters (Kimura et al., 2006) and supported by three cDNAs (AL833304, DB276457 and AK094848). AL8333304 does not encode a protein as it appears to use a "non canonical" splice site at 123781503, 4 nucleotides after initiator codon for the TACC2 "long isoforms". DB276457 appears to be incomplete at the 3 end due to the nature of its isolation (Kimura et al., 2006).


Atlas Image


Ten isoforms are predicted based on published cDNA sequences. Features will be referenced to their location in the largest AAO62630 isoform (2948 amino acids, 309403,40 Da). The nine other isoforms are: AAI44600, 2875 amino acids, 302586,86 Da; AAI44601, 2826 amino acids, 296742,08 Da; AAO62629, 1094 amino acids, 119330,60 Da; AAC64968, 1026 amino acids, 112110,91 Da; AAH39311, 996 amino acids, 108703,96 Da; BAH12132, 601 amino acids, 64367,07 Da; AAF29537, 906 amino acids, 99590,14 Da; ORF-BC015736 (longest open reading frame of GB:BC015736), 575 amino acids, 64675,57 Da; AAF63433, 571 amino acids, 64156,01 Da.
ORF-BC015736 and AAF63433, beginning at an "internal" AUG present in exon 9, are identical except for 4 amino acids missing in AAF63433 (amino acid 2429-2432). BAH12132 prematurely terminates due to a C-T mutation in the cDNA generating a nonsense codon; the partial cDNA coding this open reading frame is identical to other TACC2 isoforms downstream of the nonsense codon, suggesting the mutation is a cloning artefact.
Western blot analysis confirms the large ≈ 300 kDa isoforms and those of ≈ 100 kDa. Western blot often shows species 65-70 kDa (corresponding in size to ORF-BC015736 and AAF63433 isoforms), however the variability in intensity in different preparations from the same cell type suggests that these species could also arise as a product of degradation (PEST sequences support that TACC2 is subject to regulated degradation).
PSORT II predicts multiple nuclear localisation signals between amino acid 2128 and 2420 (http://psort.hgc.jp/form2.html). Multiple phosphorylation sites have been identified throughout the protein sequence by mass spectrometry (summarized at PhosphoSitePlus (Hornbeck et al., 2012)). The following lysine modifications are noted: lysine trimethylation at K1339 and K1346 (Cao et al., 2013); ubiquitylation at K2542 in HCT116 colon cancer cells (Kim et al., 2011); acetylation at K2884 in A549 lung cancer cells (Choudhary et al., 2009), K2736 in a resected liver cancer, K2927 and K2928 in NCI H2228 non small cell lung cancer cells (Hornbeck et al., 2012).


Short isoforms (100-120 kDa) widely expressed in fetal and adult tissue, but large isoforms (≈ 300 kDa) expressed at high levels in muscle tissue (Lauffart et al., 2003). Short form(s) expression is upregulated by erythopoietin in human microvascular endothelial cells (Pu et al., 2001) and androgens in prostate cancer cells (Takayama et al., 2012). Induction of large forms occurs as development proceeds in the tissues that express them (Still et al., unpublished).


TACC2 short isoforms can be located in the nucleus and/or cytosol of interphase cells (Chen et al., 2000; Gergely et al., 2000; Lauffart et al., 2003). TACC2 interacts with the centrosome and mitotic spindle during mitosis (Gergely et al., 2000). In some cells, overexpression can result in accumulation of the protein into cytoplasmic punctate structures due to oligmerisation (Gergely et al., 2000). The oligomerisation motif is located between amino acid 2740 and 2815 (Tei et al., 2009).


TACC2 plays a role in microtubule dynamics during mitosis based upon interactions with Aurora C kinase (Tien et al., 2004) and CKAP5 (ch-TOG/XMAP215) via the TACC domain (see Peset and Vernos, 2008 for Review). TACC2 is implicated in G2/M progression (Takayama et al., 2012) and its ability to function in the maintenance of normal mitotic spindle dynamics is targeted by SV40 T-antigen (Tei et al., 2009). TACC2 is an effector of a mitotic checkpoint control kinase, TTK, with disruption of TTK activity preventing phosphorylation of 100-120 kD TACC2 short isoforms, subsequent recruitment of the TACC2 to the centrosome, leading to reduction of centrosome-centrosome distance in mitotic cells (Dou et al., 2004). TACC2 also interacts with mitotic regulatory proteins Haus 1, Haus 4 and PRC1 (Hutchins et al., 2010).
Alternative functions have been ascribed in transcription through direct interaction with coregulators FHL2 and FHL3 proteins (Lauffart et al., 2007b), YEATS4 (GAS41) and the SWI/SNF chromatin remodeling complex (Lauffart et al., 2002), histone acetyltransferases KAT2A (hGCN5L2)/KAT2B (pCAF)/Ep300/CREBBP (Gangisetty et al., 2004), a core component of a histone deacetylase complex, HMG20B (BRAF35) (Stelzl et al., 2005) and the retinoid-X receptor (Vettaikkorumakankauv et al., 2008). TACC2 enhances transcriptional regulation from a cAMP response element (Lauffart et al., 2007b), and retinoid-X-receptor responsive genes (Vettaikkorumakankauv et al., 2008). Interaction with nucleoporin NUP155 has been identified by mass throughput technologies (Havugimana et al., 2012).
TACC2 is found in complexes containing BRCA1, BARD1, p53 and Ku70 and may therefore also have a role in DNA damage/repair (Lauffart et al., 2007a).
TACC2 is phosphorylated during mitosis (Dephoure et al., 2008; Olsen et al., 2010) and in response to activation of EGFR and oncogenic signaling pathways (Rikova et al., 2007; Chen et al., 2009; Moritz et al., 2010). Tumour suppressive properties of TACC2 are thought to function through the PLCγ pathway (Cheng et al., 2011). PPP1CC, protein phosphatase 1 may be involved in dephosphorylation of TACC2 (Esteves et al., 2013). Acetylation, ubiquitylation and trimethylation of TACC2 may also impact TACC2s function (Choudhary et al., 2009; Kim et al., 2011; Hornbeck et al., 2012; Cao et al., 2013).


Member of the TACC family, based on the presence of the conserved approximately 200 amino acid carboxy terminal coiled coil domain (TACC domain) (Still et al., 1999; Still et al., 2004). Both TACC1 and TACC2 contain a 16 amino acid SFP motif SSDSE-X2- FETPE-X2-TP, and a conserved string of nine amino acids, HATDEEKLA. These two motifs are specific to TACC1 and 2 only. Additionally, TACC2 contains two copies of the 33 amino acid SDP repeat, which is conserved between the members of the vertebrate TACC family (Lauffart et al., 2002). In TACC1, the SDP repeat serves as the binding site for the SWI/SNF component/accessory factor, YEATS4 (Lauffart et al., 2002).



To date, no mutations in the TACC2 gene have been detected.

Implicated in

Entity name
Infant acute lymphoblastic leukemia
In a gene array analysis of 97 patients, increased expression was correlated with an intermediate or high risk for a poorer outcome, independent of patient age (Kang et al., 2012). Results were not confirmed at the protein level.
Upregulation of TACC2 may be triggered by the underlying alteration in the MLL gene in patients, resulting in recruitment of histone methylases to target genes. Proposed mechanism based on previous identification of the regulation of the TACC2 gene by the histone methylase SMYD2 (Abu-Farha et al., 2008).
Entity name
Identified as a marker of minimal residue disease based on Affymetrix U-95 gene chip expression array analysis of 48 stage 4 tumours and 9 remission bone marrows. Expression of TACC2 in tumour as compared to marrow was superior to that of tyrosine hydroxylase, however, TACC2 expression failed to be of prognostic value for progression-free survival (Cheung et al., 2008).
Entity name
Intracranial ependymoma
Single allele deletion detected by high-resolution matrix-based CGH in 11/68 intracranial ependymoma (Mendrzyk et al., 2006), not linked to clinicopathologic subgroups.
Apparent overexpression from remaining allele in the tumours observed by qRT-PCR (Mendrzyk et al., 2006).
Entity name
Breast cancer
Decreased expression of TACC2 was noted in a survey of breast cancer samples by immunohistochemistry of tumour microarrays derived from 552 breast cancer patients (Jacquemier et al., 2005). In another study, "increased" levels of TACC2 were reported, based on quantitative rt-PCR and analysis of protein levels in "macro-dissected" tumours, to be associated with poorer prognosis, grade and short disease-free survival (Cheng et al., 2010). However, the intensity of immunohistochemical staining of the tumour cells appeared to be the same as in normal breast epithelium used in the study. Thus, in this study, TACC2 staining may only reflect the percentage of the resected tumour tissue occupied by tumour cells and may reflect retention of expression of TACC2 at normal levels seen in the precursor mammary epithelial cells (Cheng et al., 2010).
The TACC2 transcript AF176646 (AZU1) is downregulated in the more malignant derivatives of the HMT-3522 tumour progression cell model (Chen et al., 2000). Expression of exogenous TACC2 short isoforms (AF176646, AF095791 or AF528098) reduces malignant potential of breast tumour cells (Chen et al., 2000; Lauffart et al., 2003). Tumor suppressor properties may operate through PLCγ (Cheng et al., 2011).
Entity name
Prostate cancer
Positive correlation between Gleason score and immunohistochemical staining for TACC2 noted in a survey of 103 prostate cancer samples (Takayama et al., 2012).
The TACC2 gene is androgen responsive, with two confirmed androgen receptor binding sites in intron 4*; at 123870283-123870871 (Takayama et al., 2012). TACC2 promotes cell proliferation in androgen sensitive and androgen-independent prostate cancer cells. A single-nucleotide polymorphism, rs3763763, inside an estrogen response element is associated with prostate cancer-specific mortality and "all-cause mortality" after androgen-deprivation therapy (Huang et al., 2012) suggesting that hormonally regulated expression of TACC2 is important in the oncogenic process. It has been noted that TACC2 interacts with androgen receptor regulator FHL2 (Lauffart et al., 2007b), a protein of known importance in attainment of androgen independence in prostate cancer (McGrath et al., 2013), suggesting potential positive feedback on TACC2 expression.
*designated based on genomic structure of the AF528099 long form (see genomic model).



No translocation or deletions within the TACC2 gene have been identified.


Pubmed IDLast YearTitleAuthors
180657562008The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase.Abu-Farha M et al
236445102013Large-scale global identification of protein lysine methylation in vivo.Cao XJ et al
107499352000AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression.Chen HM et al
192763682009CDC25B mediates rapamycin-induced oncogenic responses in cancer cells.Chen RQ et al
203355202010Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance.Cheng S et al
189809982008Exploiting gene expression profiling to identify novel minimal residual disease markers of neuroblastoma.Cheung IY et al
196088612009Lysine acetylation targets protein complexes and co-regulates major cellular functions.Choudhary C et al
186696482008A quantitative atlas of mitotic phosphorylation.Dephoure N et al
153043232004TTK kinase is essential for the centrosomal localization of TACC2.Dou Z et al
215262222011A user's guide to the encyclopedia of DNA elements (ENCODE).
230800692013Protein phosphatase 1γ isoforms linked interactions in the brain.Esteves SL et al
147674762004The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases.Gangisetty O et al
111210382000The TACC domain identifies a family of centrosomal proteins that can interact with microtubules.Gergely F et al
229396292012A census of human soluble protein complexes.Havugimana PC et al
221352982012PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse.Hornbeck PV et al
218800742012Genetic polymorphisms in oestrogen receptor-binding sites affect clinical outcomes in patients with prostate cancer receiving androgen-deprivation therapy.Huang CN et al
203600682010Systematic analysis of human protein complexes identifies chromosome segregation proteins.Hutchins JR et al
157058732005Protein expression profiling identifies subclasses of breast cancer and predicts prognosis.Jacquemier J et al
222108792012Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study.Kang H et al
219069832011Systematic and quantitative assessment of the ubiquitin-modified proteome.Kim W et al
163445602006Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.Kimura K et al
184812062007Interaction of TACC proteins with the FHL family: implications for ERK signaling.Lauffart B et al
238017472013Regulation of the transcriptional coactivator FHL2 licenses activation of the androgen receptor in castrate-resistant prostate cancer.McGrath MJ et al
166090182006Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma.Mendrzyk F et al
207364842010Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases.Moritz A et al
200682312010Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.Olsen JV et al
186563602008The TACC proteins: TACC-ling microtubule dynamics and centrosome function.Peset I et al
111614552001Cloning 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.Pu JJ et al
180831072007Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.Rikova K et al
161690702005A human protein-protein interaction network: a resource for annotating the proteome.Stelzl U et al
104356271999Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon.Still IH et al
152070082004Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms.Still IH et al
224561972012TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer.Takayama K et al
196716632009Simian virus 40 large T antigen targets the microtubule-stabilizing protein TACC2.Tei S et al
146028752004Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model.Tien AC et al

Other Information

Locus ID:

NCBI: 10579
MIM: 605302
HGNC: 11523
Ensembl: ENSG00000138162


dbSNP: 10579
ClinVar: 10579
TCGA: ENSG00000138162


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
185198262008Molecular genetics of successful smoking cessation: convergent genome-wide association study results.130
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
222108792012Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study.41
224561972012TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer.19
126203972003Molecular cloning, genomic structure and interactions of the putative breast tumor suppressor TACC2.18
147674762004The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases.17
205089832011Centrosome-related genes, genetic variation, and risk of breast cancer.16
153043232004TTK kinase is essential for the centrosomal localization of TACC2.9
203355202010Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance.9


Ivan H Still ; Brenda Lauffart

TACC2 (transforming, acidic coiled-coil containing protein 2)

Atlas Genet Cytogenet Oncol Haematol. 2013-08-01

Online version: http://atlasgeneticsoncology.org/gene/42457/tacc2