The human NDC80 gene lies on the p arm of chromosome 18, close to the telomeric region; Position 2,571,511 to 2,616,635, forward strand (Ensembl ID: ENSG00000080986).

The full mRNA comprises 2172 bp (Ensembl ID: ENST00000261597.8). The transcript contains 17 exons. Ensembl reports the existence of 5 splice variants. Analysis of the 5-flanking region showed that it contains binding sites for cAMP responsive element binding (CREB) and activating transcription factor 4 (ATFA or CREB 2) proteins that positively regulate transcription (Cheng et al, 2007).

No pseudogenes are described in humans.

642 aa; 73.9 kDa.
"Highly Expressed in Cancer protein 1" (Hec1) is the name of the human homologue of the Ndc80 protein. It was originally identified as an interactor of the retinoblastoma (pRb) protein in the yeast two-hybrid system (Chen et al, 1997). It was subsequently re-isolated as an interactor of the mitotic checkpoint protein MAD1L1 (Martin-Lluesma et al, 2002).
Hec1 interacts with three other kinetochore proteins ( NUF2, SPC25 and SPC24 ) to form the Ndc80 kinetochore complex that is required for establishing stable interactions between the kinetochore and microtubules (Ciferri et al, 2005; DeLuca et al, 2006; DeLuca & Musacchio, 2012). The complex has an elongated rod-like structure that spans ~60 nm, with globular domains at both ends. The globular domains of Nuf2 and Hec1 interact with the microtubules at one end whereas the Spc24-Spc25 globular heads constitute the centromere binding domain of the complex
The crystal structure of a truncated version of the Ndc80 complex has been resolved and different Hec1 structural domains have been identified (Ciferri et al, 2008). The N-terminus comprises an unstructured tail domain (aa 1-80) which is highly basic and positively charged. The Hec1 tail is required for the efficient formation of stable kinetochore-microtubule attachments in mammalian cultured cells (Guimaraes et al, 2008; Miller et al, 2008) and the affinity for microtubules of the entire complex is modulated by AURKB (Aurora B)-mediated phosphorylation on Ser8, Ser44, Ser15, Ser55 residues within the tail domain
A second portion of the N terminus folds into a Calponin Homology (CH) domain (aa 81-196), a motif found in actin- and microtubule-binding proteins. The CH domain contributes to microtubule binding and attachment stability through a direct interaction between a positively charged regionin the CH domain and a negative region at the alpha and beta tubulin interface on microtubules (Alushin et al, 2010). Within the CH domain, Ser165 is phosphorylated by the mitotic NEK2 (NEK2A) kinase and expression of a non -phosphorylatable Hec1 has been shown to perturb chromosome congression and increase the number of erroneous kinetochore-microtubule interactions (Du et al, 2008).
The long coiled-coil region (aa 261-445) interacts with a similar region of Nuf2 producing the elongated rod-like structure. This domain is interrupted by a loop region in Ndc80 (aa 426-459), forming a kink in the Ndc80 complex structure. This region is required to establish end-on microtubule attachments to kinetochores through the binding of the spindle and kinetochore associated (Ska) complex and the Ctd1 replication licensing factor (Wan et al, 2009; Zhang et al, 2012; Varma et al, 2012). Finally, the C terminus (446-642) takes part in a tetramerization domain where the Ndc80/Nuf2and Spc24/Spc25 dimers interact (Ciferri et al, 2005).

The protein is present in actively proliferating tissues such as testis, spleen and thymus in mice (Chen et al, 1997). Hec1 expression is cell cycle regulated. In both untransformed and cultured cancer cells, the protein appears in late S and remains at high levels until mitosis, when it is down-regulated through anaphase promoting complex/cyclosome-Cdh1 (APC/C-Cdh1) and proteasome-mediated degradation  (Li et al, 2011; Ferretti et al, 2010).

Hec1 is a mitotic kinetochore protein. It localizes to nuclei in S phase and G2 cells. At the beginning of mitosis the protein localizes to the outer layer of the kinetochore (Wan et al, 2009), where it persists until it is degraded at the end of mitosis (Figure 1).

Kinetochore-microtubule interactions:
Faithful chromosome segregation occurs when the two sister kinetochores are connected to microtubules emanating from different spindle poles (amphitelic attachment). However, in the early stages of mitosis non functional kinetochore-microtubule interactions (syntelic and merotelic attachments) intervene and must be corrected before anaphase to impede chromosome mis-segregation and aneuploidy (Cimini & Degrassi, 2005). Hec1 is a constituent of the evolutionary conserved Ndc80/Hec1 complex that mediates the attachment of sister chromatids to the mitotic spindle and is therefore implicated in producing amphitelic end-on attachments and directing chromosome movements during mitosis (Tooley & Stukenberg, 2011). Molecular affinity beetween Hec1 and microtubules is mediated by electrostatic interactions involving positively charged amino acid residues on the Hec1 tail and CH domain that interact with negatively charged residues on microtubules (Ciferri et al, 2008; Sundin et al, 2011; Tooley et al, 2011). Consequently, the temporally regulated phosphorylation of Hec1 N terminal tail by Aurora B kinase during prometaphase decrease the affinity of the Ndc80 complex to microtubules, allowing the detachment of erroneous kinetochore-microtubule interactions and enabling the formation of new correct attachments (Zaytsev et al, 2014; DeLuca et al, 2011). Phosphorylation by NEK2A kinase of the CH domain also contributes to this process . Finally, kinetochore-microtubule attachments are stabilized by the recruitment of the Ska complex and Cdt1 at the Ndc80 internal loop to form functional end-on attachments (Zhang et al, 2012; Varma et al, 2012).
Mitotic checkpoint signaling :
Several pieces of evidence indicate that Hec1 plays a positive role in the spindle assembly checkpoint (SAC). This conserved cellular mechanism inhibits anaphase onset until all kinetochores are amphitelically attached to the microtubules and inter-kinetochore tension is present . Unattached kinetochores recruit SAC components that are then released from kinetochores to inhibit the anaphase promoting complex/cyclosome necessary for sister chromatid separation and mitotic exit (Musacchio, 2015). The Ndc80 complex is a structural component of the kinetochore and is required for proper SAC control as it recruits the ZW10 complex (Lin et al, 2006; Kops et al, 2005) that is essential for the binding of the master checkpoint proteins MAD1L1 and MAD2L1 to kinetochore (Martin-Lluesma et al, 2002; DeLuca et al, 2003). Furthermore, Hec1 has been shown to specify the kinetochore localization of the checkpoint kinase TTK (Mps1) via its microtubule binding domain (Stucke et al, 2004; Zhu et al, 2013). Hec1 phosphorylation by Aurora B kinase weakens the kinetochore-microtubule interaction but promotes Hec1 binding to Mps1, suggesting a concerted regulation between kinetochore attachment and checkpoint signaling (Zhu et al, 2013; Hiruma et al, 2015). Significantly, recent work has shown that formation of stable kinetochore- microtubule attachments, irrespective of inter-kinetochore tension, is sufficient to satisfy the SAC in human cells (Tauchman et al, 2015)