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

Alias_names	transforming, acidic coiled-coil containing protein 2
Alias_symbol (synonym)	AZU-1
	ECTACC
Other alias
HGNC (Hugo)	TACC2
LocusID (NCBI)	10579
Atlas_Id	42457
Location	10q26.13  [Link to chromosome band 10q26]
Location_base_pair	Starts at 121989174 and ends at 122254545 bp from pter ( according to hg19-Feb_2009)  [Mapping TACC2.png]

Description	The gene is composed of 28 exons spanning 265369 bp.
Transcription	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).

Description	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).
Expression	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).
Localisation	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).
Function	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 TACC2's function (Choudhary et al., 2009; Kim et al., 2011; Hornbeck et al., 2012; Cao et al., 2013).
Homology	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).

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