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. |
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| Protein Isoforms |
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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. |
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). |
Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. |
Conte N, Charafe-Jauffret E, Delaval B, Adelaide J, Ginestier C, Geneix J, Isnardon D, Jacquemier J, Birnbaum D. |
Oncogene. 2002 Aug 15;21(36):5619-30. |
PMID 12165861 |
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TACC1-chTOG-Aurora A protein complex in breast cancer. |
Conte N, Delaval B, Ginestier C, Ferrand A, Isnardon D, Larroque C, Prigent C, Seraphin B, Jacquemier J, Birnbaum D. |
Oncogene. 2003 Nov 6;22(50):8102-16. |
PMID 14603251 |
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Transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis. |
Cully M, Shiu J, Piekorz RP, Muller WJ, Done SJ, Mak TW. |
Cancer Res. 2005 Nov 15;65(22):10363-70. |
PMID 16288026 |
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Aurora B -TACC1 protein complex in cytokinesis. |
Delaval B, Ferrand A, Conte N, Larroque C, Hernandez-Verdun D, Prigent C, Birnbaum D. |
Oncogene. 2004 Jun 3;23(26):4516-22. |
PMID 15064709 |
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FGFR1 and WT1 are markers of human prostate cancer progression. |
Devilard E, Bladou F, Ramuz O, Karsenty G, Dales JP, Gravis G, Nguyen C, Bertucci F, Xerri L, Birnbaum D. |
BMC Cancer. 2006 Nov 30;6:272. |
PMID 17137506 |
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Combined translocation with ZNF198-FGFR1 gene fusion and deletion of potential tumor suppressors in a myeloproliferative disorder. |
Etienne A, Gelsi-Boyer V, Carbuccia N, Adelaide J, Barba G, La Starza R, Murati A, Eclache V, Birg F, Birnbaum D, Mozziconacci MJ, Mecucci C, Chaffanet M. |
Cancer Genet Cytogenet. 2007 Mar;173(2):154-8. |
PMID 17321332 |
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The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases. |
Gangisetty O, Lauffart B, Sondarva GV, Chelsea DM, Still IH. |
Oncogene. 2004 Apr 1;23(14):2559-63. |
PMID 14767476 |
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The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. |
Gergely F, Draviam VM, Raff JW. |
Genes Dev. 2003 Feb 1;17(3):336-41. |
PMID 12569123 |
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The TACC domain identifies a family of centrosomal proteins that can interact with microtubules. |
Gergely F, Karlsson C, Still I, Cowell J, Kilmartin J, Raff JW. |
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14352-7. |
PMID 11121038 |
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Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer. |
Ghayad SE, Vendrell JA, Bieche I, Spyratos F, Dumontet C, Treilleux I, Lidereau R, Cohen PA. |
J Mol Endocrinol. 2009 Feb;42(2):87-103. Epub 2008 Nov 4. |
PMID 18984771 |
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Diversification of Transcriptional Modulation: Large-scale Identification and Characterization of Putative Alternative Promoters of Human Genes. |
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S. |
Genome Res. 2006 Jan;16(1):55-65. Epub 2005 Dec 12. |
PMID 16344560 |
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Interaction of TACC proteins with the FHL family: implications for ERK signaling. |
Lauffart B, Sondarva GV, Gangisetty O, Cincotta M, Still IH. |
J Cell Commun Signal. 2007b Jun;1(1):5-15. Epub 2007 Mar 28. |
PMID 18481206 |
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Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia. |
Li W, Kessler P, Williams BR. |
Oncogene. 2005 Jan 13;24(3):457-68. |
PMID 15531917 |
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Altered splicing pattern of TACC1 mRNA in gastric cancer. |
Line A, Slucka Z, Stengrevics A, Li G, Rees RC. |
Cancer Genet Cytogenet. 2002 Nov;139(1):78-83. |
PMID 12547166 |
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ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. |
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ. |
Science. 2007 May 25;316(5828):1160-6. |
PMID 17525332 |
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Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. |
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M. |
Cell. 2006 Nov 3;127(3):635-48. |
PMID 17081983 |
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Expression analysis of stage III serous ovarian adenocarcinoma distinguishes a sub-group of survivors. |
Partheen K, Levan K, Osterberg L, Horvath G. |
Eur J Cancer. 2006 Nov;42(16):2846-54. Epub 2006 Sep 22. |
PMID 16996261 |
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The TACC proteins: TACC-ling microtubule dynamics and centrosome function. |
Peset I, Vernos I. |
Trends Cell Biol. 2008 Aug;18(8):379-88. Epub 2008 Jul 23. |
PMID 18656360 |
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Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. |
Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ. |
Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. |
PMID 15592455 |
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Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. |
Still IH, Hamilton M, Vince P, Wolfman A, Cowell JK. |
Oncogene. 1999 Jul 8;18(27):4032-8. |
PMID 10435627 |
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Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms. |
Still IH, Vettaikkorumakankauv AK, DiMatteo A, Liang P. |
BMC Evol Biol. 2004 Jun 18;4:16. |
PMID 15207008 |
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The TACC proteins are coregulators of the Retinoid X Receptor beta. |
Vettaikkorumakankauv AK, Lauffart B, Gangisetty O, Cincotta MA, Hawthorne LA, Cowell JK, Still IH. |
Cancer Therapy. 2008 Dec; 6 (2): 805-816. |
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