The TPX2 locus is on the q arm of chromosome 20; position 30326904 to 30389603, forward strand (NCBI, 22974).

The 3685 bp mRNA (NCBI Reference Sequence: NM_012112.4) contains 18 exons (16 coding); the processed cDNA is of 2244 bp. Ensembl reports the existence of a second transcript, containing 1 additional exon (ENST00000340513). TPX2 is expressed in proliferating cells; the TPX2 transcript was detected at high levels in human placenta, thymus and testis, while it was barely detectable in brain, heart, lung and pancreas (Manda et al., 1999; Wang et al., 2002; Satow et al., 2010).

No pseudogenes described in humans.

747 aa; MW: 85653 Da.
Human TPX2 was initially identified as a nuclear protein of apparent molecular weight of 100 kDa expressed in proliferating cells, and named p100 (Heidebrecht et al., 1997); it was subsequently re-isolated in the search for mitotic targets of RanGTP as the homolog of X. laevis TPX2 (Gruss et al., 2001).
Human TPX2 harbours distinct functional domains:
- TPX2 is a microtubule-associated protein; both the full length protein and the N-terminus (amino acids 1-352) are able to bind microtubules in vitro (Schatz et al., 2003; Trieselmann et al., 2003). Additional regions in the C-terminus of TPX2 are involved in direct or indirect binding to microtubules in cells (Trieselmann et al., 2003). Domain characterisation of the Xenopus homolog also indicates the presence of one or more microtubule-binding domains in the N-terminus of TPX2; the C-terminal region has no direct affinity for microtubules but is required for localisation to spindle poles (Brunet et al., 2004).
- A non canonical nuclear localisation signal (NLS) centered around amino acids 314-315 (Schatz et al., 2003) mediates binding of TPX2 to importin alpha. Structural work has confirmed the association of the corresponding residues 284-287 in the Xenopus homolog protein to the "minor" NLS-binding site of importin alpha and has shown a second region (residues 327-330 of Xenopus TPX2) contacting the "major" NLS-binding site (Giesecke and Stewart, 2010).
- A KEN box (87-89) degradation motif is required for recognition by APC/C^Cdh1 (Stewart and Fang, 2005).
- The N-terminal region (residues 1-43; Bayliss et al., 2003) is required for the interaction with, and activation of, the Aurora-A kinase.
- An evolutionary conserved region of 35 amino acids at the C-terminus has been shown both in Xenopus and mouse TPX2 to bind the Eg5 kinesin (Eckerdt et al., 2008; Ma et al., 2010).

TPX2 is expressed in a cell cycle-regulated manner; it appears in S phase and protein levels remain high in G2 and mitosis, until telophase when TPX2 is down-regulated via APC/C^Cdh1-dependent degradation (Heidebrecth et al., 1997; Gruss et al., 2001; Stewart and Fang, 2005). TPX2 is differentially expressed in tumor vs non-transformed cells (see below).

TPX2 localises to nuclei of interphase cells (S and G2); after nuclear envelope breakdown it associates with spindle microtubules; in late anaphase and telophase it also localises to the spindle mid-zone (Heidebrecht et al., 1997; Gruss et al., 2002; Garrett et al., 2002; figure 1).

Spindle assembly: TPX2 is a RanGTP-regulated spindle assembly factor (Gruss et al., 2001). An important contribution to the understanding of the mechanisms through which TPX2 acts in spindle assembly has been provided by studies that made use of the Xenopus egg extract system (Gruss and Vernos, 2004 and references therein).
Evidence obtained in mammalian cells support the notion that TPX2 plays a key role in spindle formation and function. Mitotic functions of TPX2 are negatively regulated by the binding to importin alpha and beta; the presence of RanGTP, by dissociating the complex between TPX2 and import receptors, induces the release of active TPX2 (Gruss et al., 2001). Indeed, excess TPX2 is able to rescue spindle pole organisation defects induced by importin beta overexpression in human cells (Ciciarello et al., 2004), pointing out the functional antagonism between TPX2 and import receptors in spindle assembly.
TPX2 acts in spindle organisation by:
i) its direct ability to induce microtubule assemblies and to bundle microtubules (Schatz et al., 2003);
ii) its targeting function: TPX2 recruits several mitotic regulators to the spindle, i.e. the Aurora-A kinase (Kufer et al., 2002), the kinesins hklp2 (Vanneste et al., 2009; Tanenbaum et al., 2009) and Eg5 (Ma et al., 2011b) and the scaffold attachment factor A (SAF-A; Ma et al., 2011a);
iii) regulation of specific mitotic factors: TPX2 interacts with the Aurora-A kinase and activates it, by stabilising it in the active conformation (Bayliss et al., 2003); in addition, TPX2 modulates Aurora-A protein stability, by counteracting proteasome-dependent Aurora-A degradation (Giubettini et al., 2011). TPX2 also regulates the activity of the Eg5 kinesin: in vitro assays show that TPX2 reduces the rate of Eg5-dependent microtubule gliding and microtubule-microtubule sliding (Ma et al., 2011).
Consistently, its inactivation in cultured mammalian cells impairs microtubule nucleation from chromosomes, and to a lesser extent from centrosomes, as well as organisation of microtubules within the spindle and cohesion of spindle poles (Garrett et al., 2002; Gruss et al., 2002; De Luca et al., 2006; Tulu et al., 2006; Bird and Hyman, 2008).
Neurogenesis in vertebrate brain: Neural progenitor cells in the apical-most region of the neuroepithelium, or ventricular zone, exhibit interkinetic nuclear migration (INM): their nuclei migrate apically in synchrony with cell cycle progression, so that mitosis occurs at the apical surface of the ventricular zone. TPX2 has been recently reported to promote interkinetic nuclear migration in mouse neural cells, by re-organising apical microtubules during the G2 phase (Kosodo et al., 2011).
DNA damage response (DDR): recent data show that TPX2 is involved in DDR to ionising radiations, by modulating the levels of γ-H2AX; TPX2 localises to DNA double strand breaks and interacts with DDR factors such as MDC1 (Neumayer et al., 2012). Previous data suggested a link between TPX2 and DDR: i) TPX2 is a putative substrate of the ATM/ATR kinases, as revealed in a large-scale proteomic screening (Matsuoka et al., 2007); ii) a functional interplay has been shown between Xenopus TPX2, the Aurora-A kinase and the p53 oncosuppressor (Pascreau et al., 2009).

TPX2 orthologs have been identified in all classes of vertebrates, with Xenopus, mouse and human TPX2 being the best characterised. TPX2-like proteins have been described in plants (Vos et al., 2008; Evrard et al., 2009), C. elegans (Ozlü et al., 2005) and Drosophila melanogaster (Goshima, 2011).