TACC1 (transforming, acidic coiled-coil containing protein 1)
2008-12-01 Ivan Still  , Melissa R Eslinger  , Brenda Lauffart   AffiliationDNA/RNA

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.
Description
The gene is composed of 19 exons spanning 124.5kb.
Transcription
Encodes 11 confirmed splice variants in humans (Line et al., 2002; Lauffart et al., 2006). TACC1A 7735nt, TACC1A* 7521nt, TACC1B 6204nt, TACC1C 6194nt, TACC1D 6193nt,TACC1E 7345nt, TACC1F 7770nt, TACC1G 7904nt (utilizes internal splice site in exon 5), TACC1H 7319nt, TACC1I 7424nt, TACC1S 6528nt. Fully sequenced singleton cDNAs e.g. AK304507 and AK303596 suggest additional variants possible. AK304507 utilizes internal splice site in exon 5. Inclusion of alternate 5 noncoding exons indicated from expressed sequence tags identified in a global search for alternative promoters e.g. DA066351, DA950013 (Kimura et al., 2006).
Note:AK304507 and AK303596 sequences may be suspect (see UCSC Genome Bioinformatics Site (http://genome.ucsc.edu) for more details.
Transcript/isoform nomenclature as per Line et al, 2002 and Lauffart et al., 2006. TACC1F transcript includes exon 1, 2 and 3 (correction to Fig 6 of Lauffart et al., 2006).
Note:
Pseudogene
Partially processed pseudogene: 91% identity corresponding to base 596 to 2157 of AF049910.
87% identity corresponding to base 7381 to 7742 of AF049910.
- Location: 10p11.21.
- Location base pair: Starts at 37851943 and ends at 37873633 from pter (according to hg18-March_2006).
- Location: 8p21.
- Location base pair: Starts at 84786555 and ends at 84786906 from pter (according to hg18-March_2006).
Proteins
Note
11 confirmed splice variants generate 9 different protein isoforms. Two additional isoforms suggested by AK304507 and AK303596.
Inclusion of alternative promoters and 5 non coding exons produce one of these known protein isofroms e.g. transcripts defined by DA950013, or BQ888599 would produce TACC1E/H, transcripts defined by DA066351 would produce TACC1A/A* and transcripts defined by DC325260 would produce TACC1B.
Inclusion of alternative promoters and 5 non coding exons produce one of these known protein isofroms e.g. transcripts defined by DA950013, or BQ888599 would produce TACC1E/H, transcripts defined by DA066351 would produce TACC1A/A* and transcripts defined by DC325260 would produce TACC1B.

Protein Isoforms
Description
TACC1A/TACC1A*, 805 amino acids, 87.8kDa, TACC1B 243 amino acids 19.4kDa, TACC1C 367 amino acids 40.9kDa, TACC1D 379 amino acids 42.3kDa, TACC1E/H 610 amino acids 67.1kDa, TACC1F 817 amino acids 89kDa, TACC1G 731 amino acids 79.9kDa, TACC1I 777 amino acids 84kDa, TACC1S 395 amino acids 44kDa, BAG65314 792 amino acids 86.2kDa, BAG64611 476 amino acids 51.5kDa.
Expression
Wide expression in fetus and adult. Detailed analysis reported during mouse development by Lauffart et al., 2006.
Localisation
TACC1 is located in the nucleus and/or cytosol, depending on isoform and cell type (Lauffart et al., 2006). Exon 3 contains a predicted nuclear localisation signal. Most immunohistochemical analyses in sectioned tissues have used antibodies that recognize an epitope located in Exon 3. Thus, studies at the protein level have concentrated on exon 3 containing isoforms A, A*, E, F, G, H and I, but fail to differentiate between them. TACC1A weakly interacts with the centrosome during mitosis (Gergely et al., 2000). Overexpression can result in accumulation in cytoplasm in some cells resulting in oligmerisation in punctate structures (Gergely et al., 2000).
Function
TACC1 has been proposed to function in microtubule dynamics in interphase, mitosis and cytokinesis based upon interactions with Aurora A kinase and Aurora B kinase and CKAP5 (ch-TOG/XMAP215) by interactions with the TACC domain (see Pessat and Vernos 2008 for Review). TACC1A may function in RNA splicing, decapping and/or degradation through interactions with SmG (SNRPG) and LSm-7 (LSM7) via amino acids 1-53 (Conte et al., 2002). Increased expression of TACC1A in mammary gland activates ras-MAPK and PI-3K pathways (Cully et al., 2005). The former may be due in part on TACC1A-mediated retention of pERK in the cytoplasm (Lauffart et al., 2007b). Nuclear localized TACC1 is phosphorylated on S50,S52,S54,S55,S57, cytoplasmic TACC1 is phosphorylated on S275, while Y533 is phosphorylated in Jurkat cells (Rush et al., 2005, Olsen et al., 2006). Amino acids 152-258 binds to TDRD7, but function of this interaction is unknown (Conte et al., 2003). TACC1A is a possible indirect activator of CREB via FHL family of proteins (Lauffart et al., 2007b). Uncharacterized roles in transcriptional regulation have been proposed based on TACC1 binding to GAS41 (YEATS4) via amino acid 206-427, hGCN5L2 (KAT2A), FHL coactivator/corepressor proteins and retinoid X-receptor beta via the TACC domain (Gangisetty, 2004; Lauffart et al., 2002; 2007b; 2008; Vettaikkorumakankauv et al., 2008). TACC1A can interact with BARD1 in vitro, and is phosphorylated on serine residue 44 in response to DNA damage (Matsuoka et al., 2007).
Amino acid residues involved in binding or subject to phosphorylation are quoted for TACC1A, but residues, if present in other isoforms, may also be subject to the same interactions or modifications.
Amino acid residues involved in binding or subject to phosphorylation are quoted for TACC1A, but residues, if present in other isoforms, may also be subject to the same interactions or modifications.
Homology
Founding 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).
Mutations
Note
To date, no mutation of TACC1 gene have been described.
Implicated in
Entity name
Breast cancer
Prognosis
Expression associated with resistance to tamoxifen and fulvestrant and shorter relapse-free survival (Ghayad et al., 2008).
Oncogenesis
TACC1 protein downregulated in breast cancer (Conte et al., 2002). Expression retained in tamoxifen and fulvestrant resistant tumors (Ghayad et al., 2008).
Entity name
Ovarian Cancer
Prognosis
Retention of expression in Stage III tumors associated with favorable prognosis (Partheen et al., 2006).
Oncogenesis
Total cellular expression or nuclear localization lost in ovarian cancer (Lauffart et al., 2005).
Entity name
Wilms Tumor
Prognosis
Expression associated with more favorable prognosis (Li et al., 2005)
Oncogenesis
Expressed at lower levels in anaplastic versus tumors with favorable histology (Li et al., 2005).
Entity name
Gastric Cancer
Prognosis
Increased expression of TACC1D and TACC1F variants associated with gastric cancer (Line et al., 2002).
Oncogenesis
Change in splicing pattern in gastric cancer (Line et al., 2002).
Entity name
Prostate Cancer
Prognosis
Increased expression of TACC1 detected in advanced stages (pT3 and/or N1/M1) and associated with androgen-independent prostate carcinoma (Devilard et al., 2006).
Oncogenesis
TACC1 protein expression in prostate cancer noted in cytoplasm (Devilard et al., 2006), compared to nucleus in normal prostate epithelium (Lauffart et al., 2006).
Breakpoints
Note
Potential deletion as a result of translocation event associated with 8p11 myeloproliferative disorder (Etienne et al., 2007).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12165861 | 2002 | Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. | Conte N et al |
| 14603251 | 2003 | TACC1-chTOG-Aurora A protein complex in breast cancer. | Conte N et al |
| 16288026 | 2005 | Transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis. | Cully M et al |
| 15064709 | 2004 | Aurora B -TACC1 protein complex in cytokinesis. | Delaval B et al |
| 17137506 | 2006 | FGFR1 and WT1 are markers of human prostate cancer progression. | Devilard E et al |
| 17321332 | 2007 | Combined translocation with ZNF198-FGFR1 gene fusion and deletion of potential tumor suppressors in a myeloproliferative disorder. | Etienne A et al |
| 14767476 | 2004 | The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases. | Gangisetty O et al |
| 12569123 | 2003 | The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. | Gergely F et al |
| 11121038 | 2000 | The TACC domain identifies a family of centrosomal proteins that can interact with microtubules. | Gergely F et al |
| 18984771 | 2009 | Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer. | Ghayad SE et al |
| 16344560 | 2006 | Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. | Kimura K et al |
| 18481206 | 2007 | Interaction of TACC proteins with the FHL family: implications for ERK signaling. | Lauffart B et al |
| 15531917 | 2005 | Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia. | Li W et al |
| 12547166 | 2002 | Altered splicing pattern of TACC1 mRNA in gastric cancer. | Line A et al |
| 17525332 | 2007 | ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. | Matsuoka S et al |
| 17081983 | 2006 | Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. | Olsen JV et al |
| 16996261 | 2006 | Expression analysis of stage III serous ovarian adenocarcinoma distinguishes a sub-group of survivors. | Partheen K et al |
| 18656360 | 2008 | The TACC proteins: TACC-ling microtubule dynamics and centrosome function. | Peset I et al |
| 15592455 | 2005 | Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. | Rush J et al |
| 10435627 | 1999 | Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. | Still IH et al |
| 15207008 | 2004 | Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms. | Still IH et al |
Other Information
Locus ID:
NCBI: 6867
MIM: 605301
HGNC: 11522
Ensembl: ENSG00000147526
Variants:
dbSNP: 6867
ClinVar: 6867
TCGA: ENSG00000147526
COSMIC: TACC1
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 35307914 | 2022 | LINC01140 inhibits nonsmall cell lung cancer progression and cisplatin resistance through the miR-4742-5p/TACC1 axis. | 2 |
| 35307914 | 2022 | LINC01140 inhibits nonsmall cell lung cancer progression and cisplatin resistance through the miR-4742-5p/TACC1 axis. | 2 |
| 33481389 | 2021 | Neurofibrosarcoma Revisited: An Institutional Case Series of Uterine Sarcomas Harboring Kinase-related Fusions With Report of a Novel FGFR1-TACC1 Fusion. | 8 |
| 33481389 | 2021 | Neurofibrosarcoma Revisited: An Institutional Case Series of Uterine Sarcomas Harboring Kinase-related Fusions With Report of a Novel FGFR1-TACC1 Fusion. | 8 |
| 25297519 | 2014 | Prognosis significance of HER2 status and TACC1 expression in patients with gastric carcinoma. | 2 |
| 25297519 | 2014 | Prognosis significance of HER2 status and TACC1 expression in patients with gastric carcinoma. | 2 |
| 23354013 | 2013 | Efficient downregulation of ErbB-2 induces TACC1 upregulation in breast cancer cell lines. | 2 |
| 24358147 | 2013 | Impact of NPM, TFF3 and TACC1 on the prognosis of patients with primary gastric cancer. | 11 |
| 23354013 | 2013 | Efficient downregulation of ErbB-2 induces TACC1 upregulation in breast cancer cell lines. | 2 |
| 24358147 | 2013 | Impact of NPM, TFF3 and TACC1 on the prognosis of patients with primary gastric cancer. | 11 |
| 22837387 | 2012 | Transforming fusions of FGFR and TACC genes in human glioblastoma. | 395 |
| 22837387 | 2012 | Transforming fusions of FGFR and TACC genes in human glioblastoma. | 395 |
| 20508983 | 2011 | Centrosome-related genes, genetic variation, and risk of breast cancer. | 21 |
| 21531210 | 2011 | Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. | 18 |
| 20508983 | 2011 | Centrosome-related genes, genetic variation, and risk of breast cancer. | 21 |
Citation
Ivan Still ; Melissa R Eslinger ; Brenda Lauffart
TACC1 (transforming, acidic coiled-coil containing protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2008-12-01
Online version: http://atlasgeneticsoncology.org/gene/42456/tacc1-(transforming-acidic-coiled-coil-containing-protein-1)
