TACC1 (transforming, acidic coiled-coil containing protein 1)

2008-12-01   Ivan Still , Melissa R Eslinger , Brenda Lauffart 

Identity

HGNC
LOCATION
8p11.22
LOCUSID
ALIAS
Ga55
FUSION GENES

DNA/RNA

Atlas Image
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).
  • Pseudogene

    Partially processed pseudogene:

    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.
    Atlas Image
    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.

    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).

    Bibliography

    Pubmed IDLast YearTitleAuthors
    121658612002Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators.Conte N et al
    146032512003TACC1-chTOG-Aurora A protein complex in breast cancer.Conte N et al
    162880262005Transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis.Cully M et al
    150647092004Aurora B -TACC1 protein complex in cytokinesis.Delaval B et al
    171375062006FGFR1 and WT1 are markers of human prostate cancer progression.Devilard E et al
    173213322007Combined translocation with ZNF198-FGFR1 gene fusion and deletion of potential tumor suppressors in a myeloproliferative disorder.Etienne A et al
    147674762004The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases.Gangisetty O et al
    125691232003The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells.Gergely F et al
    111210382000The TACC domain identifies a family of centrosomal proteins that can interact with microtubules.Gergely F et al
    189847712009Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer.Ghayad SE 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
    155319172005Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia.Li W et al
    125471662002Altered splicing pattern of TACC1 mRNA in gastric cancer.Line A et al
    175253322007ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.Matsuoka S et al
    170819832006Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.Olsen JV et al
    169962612006Expression analysis of stage III serous ovarian adenocarcinoma distinguishes a sub-group of survivors.Partheen K et al
    186563602008The TACC proteins: TACC-ling microtubule dynamics and centrosome function.Peset I et al
    155924552005Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.Rush J 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

    Other Information

    Locus ID:

    NCBI: 6867
    MIM: 605301
    HGNC: 11522
    Ensembl: ENSG00000147526

    Variants:

    dbSNP: 6867
    ClinVar: 6867
    TCGA: ENSG00000147526
    COSMIC: TACC1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000147526ENST00000276520O75410
    ENSG00000147526ENST00000317827O75410
    ENSG00000147526ENST00000518415O75410
    ENSG00000147526ENST00000518809H0YBT8
    ENSG00000147526ENST00000519416E7ET87
    ENSG00000147526ENST00000520340R4GMT7
    ENSG00000147526ENST00000520611B4E3H6
    ENSG00000147526ENST00000520615O75410
    ENSG00000147526ENST00000520973E7EVI4
    ENSG00000147526ENST00000521050A0A0C4DGD5
    ENSG00000147526ENST00000521528E5RI10
    ENSG00000147526ENST00000521642A0A0C4DGD3
    ENSG00000147526ENST00000521866H0YAY0
    ENSG00000147526ENST00000521935E5RJU4
    ENSG00000147526ENST00000522904E5RFM9
    ENSG00000147526ENST00000524193E5RIP3
    ENSG00000147526ENST00000524354E5RJG6

    Expression (GTEx)

    0
    50
    100
    150

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    228373872012Transforming fusions of FGFR and TACC genes in human glioblastoma.255
    207340642010A large-scale candidate gene association study of age at menarche and age at natural menopause.38
    189847712009Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer.25
    119030632002Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells.18
    121658612002Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators.17
    205089832011Centrosome-related genes, genetic variation, and risk of breast cancer.16
    125471662002Altered splicing pattern of TACC1 mRNA in gastric cancer.12
    150647092004Aurora B -TACC1 protein complex in cytokinesis.12
    215312102011Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein.8
    164963242006Temporal and spatial expression of TACC1 in the mouse and human.6

    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)