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NDC80 (NDC80, kinetochore complex component)

Written2017-10Manuela Ferrara, Francesca Degrassi
Institute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, via degli Apuli 4, 00185 Rome, Italy francesca.degrassi@uniroma1.it

Keywords NDC80, Hec1, kinetochore complex, kinetochore-microtubule attachment

(Note : for Links provided by Atlas : click)

Identity

Alias_namesKNTC2
highly expressed in cancer, rich in leucine heptad repeats (yeast)
kinetochore associated 2
NDC80 kinetochore complex component homolog (S. cerevisiae)
Alias_symbol (synonym)HEC
HEC1
hsNDC80
TID3
Other aliasHsHec1
commonly known as Hec1 in humans.
HGNC (Hugo) NDC80
LocusID (NCBI) 10403
Atlas_Id 41095
Location 18p11.32  [Link to chromosome band 18p11]
Location_base_pair Starts at 2571511 and ends at 2616635 bp from pter ( according to hg19-Feb_2009)  [Mapping NDC80.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Description 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).
Transcription 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).
Pseudogene No pseudogenes are described in humans.

Protein

Description 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).
Expression 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).
Localisation 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).
 
  Fig 1. Hec1 localization in human cells. Immunofluorescence images of HeLa cells stained with DAPI (blue) and anti-Hec1 antibody (red). Hec1 is nuclear in interphase G2 cells, localizes to kinetochores at all mitotic stages and is degraded from kinetochores at telophase.
Function 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)

Implicated in

  
Entity Various Cancer
Oncogenesis Ndc80/Hec1 is a constituent of the NDC80 complex. The complex is required for accurate chromosome segregation in mitosis, as it is essential for generating bipolar end-on kinetochore-microtubule attachments, which are responsible for the faithful anaphase segregation of sister chromatids (DeLuca & Musacchio, 2012). Chromosome mis-segregation results in genome instability, which is a hallmark of cancer. The crucial role of the NDC80 complex in chromosome segregation during mitosis, the recurrent HEC1 upregulation in different human cancers (as described in sections below) and its dependence on pRb deficiency (Ferretti et al, 2010) suggest that Hec1 deregulation may be an important step in the multistage process of tumorigenesis. Concordantly, Hec1 depletion by RNa interference (RNAi) leads to defective mitotic checkpoint signaling, defective chromosome alignment to the metaphase plate and massive chromosome mis-segregation and apoptosis (Martin-Lluesma et al, 2002; Kaneko et al, 2009; Mattiuzzo et al, 2011; Linton et al, 2014; Ju et al, 2017). Interestingly, Hec1 overexpression in an inducible mouse model has been shown to promote chromosome instability in embryonic fibroblasts and tumor formation in different mouse tissues (Diaz-Rodriguez et al, 2008). Moreover, NDC80 is one of the genes defining a 11 gene signature associated with poor prognosis in multiple cancer types (Glinsky et al, 2005). This signature identifies a metastasis-enabling, anoikis-resistant, aneuploid-prone phenotype (Glinsky, 2006).
  
  
Entity Breast Cancer
Oncogenesis A real-time reverse transcription polymerase chain reaction (RT-PCR) study investigated expression of 76 mitotic spindle checkpoint genes in a large panel of breast tumor samples (including normal breast tissues, benign breast tumors, ductal carcinoma in situ, and grade I and III invasive ductal breast tumors). The study identified NDC80/Hec1 as one of the genes markedly upregulated in ductal grade III breast tumors. More interestingly, Ndc80 was specifically involved in the transition from normal breast tissues to benign breast tumors. Indeed, it was found as the most strongly upregulated gene in benign breast tumors, being its levels > 3-fold higher in begnin tumors than in normal breast tissues (Bièche et al, 2011). Moreover, NDC80 is part of several multigene expression profiles, which are commonly used in clinical settings to characterize breast cancer tissues for individualization of therapy (Koleck & Conley, 2016).
A study on the relationships between host single-nucleotide polymorphisms (SNPs) and pretreatment cognitive performance in post-menopausal women diagnosed with early stage breast cancer has identified Ndc80 as one of 22 genes with a positive association between host polymorphisms and improvement in cognitive function performance (Koleck et al, 2017).
  
  
Entity Pancreatic Cancer
Oncogenesis NDC80 mRNA and protein have been found overexpressed in pancreatic cancer tissues and in pancreatic cancer cell lines (Meng et al, 2015). Immunohistochemical evaluation of human pancreatic cancer tissues suggested that Ndc80 overexpression is significantly associated with clinicopathological parameters, including pathological T staging and N staging, which are predictors of poor prognosis (Meng et al, 2015).
  
  
Entity Liver Cancer
Oncogenesis NDC80 expression has been analyzed by RT-PCR in 42 paired hepatocellular carcinoma (HCC) and adjacent tissues. The study has revealed that NDC80 levels are significantly higher in HCC cells as compared with adjacent tissues (Ju et al, 2017). A gene expression profile dataset of 10 HCC and 10 control samples analysed for gene ontology has identified NDC80 as member of a group of cell division-related genes that are up-regulated in HCC. Moreover, Ndc80 has been identified as an "hub" protein in HCC cancer, as revealed by protein-protein interaction network construction and module detection using the STRING online tool (Yan et al, 2017).
  
  
Entity Gastric Cancer
Oncogenesis mRNA overexpression of the four genes comprising the Ndc80 complex has been observed in primary resected gastric cancers when compared with the corresponding normal mucosae (Kaneko et al, 2009). More recently, RT-PCR and immunohistochemical staining of 42 gastric cancer and paired non-cancer tissues showed higher expression of both Hec1 mRNA and protein in gastric cancers as compared with non-tumor tissues. Hec1 staining was observed in 90% of cancer samples whereas positive staining was rarely observed in non cancer tissues. Positive staining of Hec1 was also observed in dysplasia glands, a precancerous lesion, suggesting an important role of Hec1 in the early stage of gastric tumorigenesis (Qu et al, 2014).
  
  
Entity Prostate Cancer
Oncogenesis Hec1 mRNA overexpression has been detected in human Prostate Cancer (PCa) tissues and higher mRNA and protein levels have been found in several PCa cell lines (Wang et al, 2015). The same study has also identified a long-non-coding RNA (LncRNA BX647187) as up-regulated in human PCa tissues and cell lines. The study also showed that LncRNA levels are positively regulated by Hec1, as they were strongly reduced upon Hec1 depletion. Interestingly, suppression of BX647187 significantly reduced cell proliferation and promoted apoptosis of PCa cells (Wang et al, 2015).
  
  
Entity Colon cancer
Oncogenesis Overexpression of Ndc80 mRNA has been reported in colorectal cancer tissues (Kaneko et al, 2009; Miyata et al, 2015). High levels of Ndc80 protein have been also observed in several colon cancer cell lines (Xing et al, 2016). Immunohistochemical analysis on tissue samples demonstrated that the rate of Ndc80-positive cells was significantly higher in colon cancer specimens than in normal colon tissues. Faster cell proliferation and greater migration ability was observed in colorectal SW480 cells transfected with an Ndc80-expressing vector as compared to controls (Xing et al, 2016).
  
  
Entity Oligodendrogliomas
Oncogenesis A study of microarray and RNA sequencing on normal brain tissue as compared to grade II and III oligodendrogliomas (ODs) has identified a co-expression network of six mitosis-regulating genes (NDC80 is among these) associated with malignant progression and prognosis in ODs. Validation by quantitative PCR of the six gene network has been obtained in a second group of ODs patients. (Liu et al, 2015).
  
  
Entity Lung Cancer
Oncogenesis Co-overexpression of Nuf2 and Ncd80, members of the evolutionarily conserved centromere protein complex (Ndc80), has been found in non-small cell lung carcinomas (NSCLC) and NSCLC cell lines (Hayama et al, 2006). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of the two proteins in the great majority of lung cancers of various histological types (Hayama et al, 2006). The same study demonstrated that NSCLC patients with abundant expression of Nuf2/Ndc80 experience a shorter tumor-specific survival period (Hayama et al, 2006).
  
  
Entity Ovarian Cancer
Oncogenesis A RNA interference lethality screen of the human druggable genome has identified NDC80 among the four genes with a role in growth or survival of ovarian cancer cell lines. The study demonstrated that ovarian tumorigenic cells are comparatively more vulnerable to Ndc80 down-regulation compared with non-tumorigenic cells. Finally, Ndc80 was found overexpressed in nearly 100% of the samples in two independent cohorts of patient samples (Sethi et al, 2012).
  
  
Entity Endometrial Cancer
Oncogenesis A study of cDNA microarray has identified NDC80 as an up-regulated gene in serous endometrial adenocarcinomas. NDC80 was found to be member of a cluster of 46 genes exhibiting >2-fold differences in expression between serous endometrial adenocarcinomas and endometrioidones. Quantitative PCR and immunohistochemistry for Ndc80 confirmed the array results. Using unsupervised and supervised statistical analyses, this gene cluster has been demonstrated to statistically differentiate the two types of adenocarcinomas (Chen et al, 2011).
  

To be noted

Aneuploidy and chromosome instability are strongly involved in tumorigenesis. It has been demonstrated that aneuploidy may also act as a tumor suppressive mechanism, depending on the tissue analyzed and its intrinsic chromosome instability (Weaver et al. 2007; Janssen and Medema 2013).
Since the crucial role of Hec1 in chromosome segregation, it represents a promising molecular target for developing new therapeutic approaches and molecules that exert their anticancer property by producing massive aneuploidy and cell death in cancer cells. Concordantly, expression of a Hec1 protein modified at its N-terminus, the region of interaction with microtubules, has been shown to massively kill cancer cells both in vitro and in tumor xenografts (Orticello et al, 2014; Mattiuzzo et al, 2011).
Several RNAi studies have provided direct demonstration of the anti-proliferative effects of Hec1 inactivation in cancer cell lines from different tumor types such as mesothelioma (Linton et al, 2014), NSCLC (Hayama et al, 2006), prostate (Wang et al, 2015), gastric (Qu et al, 2014), hepatocellular (Ju et al., 2015) or pancreatic cancer (Meng et al, 2015). Hec1 depletion by RNAi has also been found to inhibit tumor growth in mouse xenografts (Gurzov & Izquierdo, 2006; Li et al, 2007).
In the recent years, several approaches have been undertaken to target Hec1 by inhibitory small molecules. Given the role of the NEK2A-dependent phosphorylation of Hec1 in the SAC, small molecules capable of disturbing NEK2A-Hec1 interaction have been identified and optimized by different groups (Wu et al, 2008; Lee et al, 2014; Huang et al, 2014a). In a different approach, a virtual screening for small molecules able to bind at the Hec1-microtubule interaction surface has been undertaken (Ferrara et al, 2017). This study identified a small molecule that produces chromosome segregation defects in cancer cells and promotes cancer cell death through mitotic catastrophe (Ferrara et al, 2017) In both approaches, the identified small molecules significantly reduced tumor growth in xenograft models (Huang et al, 2014b; Wu et al, 2008; Ferrara et al, 2017).

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The NDC80 complex proteins Nuf2 and Hec1 make distinct contributions to kinetochore-microtubule attachment in mitosis
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Mol Biol Cell 2011 Mar 15;22(6):759-68
PMID 21270439
 
Stable kinetochore-microtubule attachment is sufficient to silence the spindle assembly checkpoint in human cells
Tauchman EC, Boehm FJ, DeLuca JG
Nat Commun 2015 Dec 1;6:10036
PMID 26620470
 
The Ndc80 complex: integrating the kinetochore's many movements
Tooley J, Stukenberg PT
Chromosome Res 2011 Apr;19(3):377-91
PMID 21311965
 
The Ndc80 complex uses a tripartite attachment point to couple microtubule depolymerization to chromosome movement
Tooley JG, Miller SA, Stukenberg PT
Mol Biol Cell 2011 Apr 15;22(8):1217-26
PMID 21325630
 
Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore-microtubule attachment
Varma D, Chandrasekaran S, Sundin LJ, Reidy KT, Wan X, Chasse DA, Nevis KR, DeLuca JG, Salmon ED, Cook JG
Nat Cell Biol 2012 May 13;14(6):593-603
PMID 22581055
 
Protein architecture of the human kinetochore microtubule attachment site
Wan X, O'Quinn RP, Pierce HL, Joglekar AP, Gall WE, DeLuca JG, Carroll CW, Liu ST, Yen TJ, McEwen BF, Stukenberg PT, Desai A, Salmon ED
Cell 2009 May 15;137(4):672-84
PMID 19450515
 
The mitotic regulator Hec1 is a critical modulator of prostate cancer through the long non-coding RNA BX647187 in vitro
Wang H, Gao X, Lu X, Wang Y, Ma C, Shi Z, Zhu F, He B, Xu C, Sun Y
Biosci Rep 2015 Nov 26;35(6)
PMID 26612002
 
Aneuploidy acts both oncogenically and as a tumor suppressor
Weaver BA, Silk AD, Montagna C, Verdier-Pinard P, Cleveland DW
Cancer Cell 2007 Jan;11(1):25-36
PMID 17189716
 
Small molecule targeting the Hec1/Nek2 mitotic pathway suppresses tumor cell growth in culture and in animal
Wu G, Qiu XL, Zhou L, Zhu J, Chamberlin R, Lau J, Chen PL, Lee WH
Cancer Res 2008 Oct 15;68(20):8393-9
PMID 18922912
 
NDC80 promotes proliferation and metastasis of colon cancer cells
Xing XK, Wu HY, Chen HL, Feng HG
Genet Mol Res 2016 May 6;15(2)
PMID 27173328
 
Aberrant expression of cell cycle and material metabolism related genes contributes to hepatocellular carcinoma occurrence
Yan H, Li Z, Shen Q, Wang Q, Tian J, Jiang Q, Gao L
Pathol Res Pract 2017 Apr;213(4):316-321
PMID 28238542
 
Accurate phosphoregulation of kinetochore-microtubule affinity requires unconstrained molecular interactions
Zaytsev AV, Sundin LJ, DeLuca KF, Grishchuk EL, DeLuca JG
J Cell Biol 2014 Jul 7;206(1):45-59
PMID 24982430
 
The Ndc80 internal loop is required for recruitment of the Ska complex to establish end-on microtubule attachment to kinetochores
Zhang G, Kelstrup CD, Hu XW, Kaas Hansen MJ, Singleton MR, Olsen JV, Nilsson J
J Cell Sci 2012 Jul 1;125(Pt 13):3243-53
PMID 22454517
 
Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore
Zhu T, Dou Z, Qin B, Jin C, Wang X, Xu L, Wang Z, Zhu L, Liu F, Gao X, Ke Y, Wang Z, Aikhionbare F, Fu C, Ding X, Yao X
J Biol Chem 2013 Dec 13;288(50):36149-59
 

Citation

This paper should be referenced as such :
Ferrara M, Degrassi F
NDC80 (NDC80, kinetochore complex component);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/NDC80ID41095ch18p11.html


External links

Nomenclature
HGNC (Hugo)NDC80   16909
Cards
AtlasNDC80ID41095ch18p11.txt
Entrez_Gene (NCBI)NDC80  10403  NDC80, kinetochore complex component
AliasesHEC; HEC1; HsHec1; KNTC2; 
TID3; hsNDC80
GeneCards (Weizmann)NDC80
Ensembl hg19 (Hinxton)ENSG00000080986 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000080986 [Gene_View]  chr18:2571511-2616635 [Contig_View]  NDC80 [Vega]
ICGC DataPortalENSG00000080986
TCGA cBioPortalNDC80
AceView (NCBI)NDC80
Genatlas (Paris)NDC80
WikiGenes10403
SOURCE (Princeton)NDC80
Genetics Home Reference (NIH)NDC80
Genomic and cartography
GoldenPath hg38 (UCSC)NDC80  -     chr18:2571511-2616635 +  18p11.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)NDC80  -     18p11.32   [Description]    (hg19-Feb_2009)
EnsemblNDC80 - 18p11.32 [CytoView hg19]  NDC80 - 18p11.32 [CytoView hg38]
Mapping of homologs : NCBINDC80 [Mapview hg19]  NDC80 [Mapview hg38]
OMIM607272   
Gene and transcription
Genbank (Entrez)AF017790 AK289396 AK313184 BC005239 BC010171
RefSeq transcript (Entrez)NM_006101
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)NDC80
Cluster EST : UnigeneHs.414407 [ NCBI ]
CGAP (NCI)Hs.414407
Alternative Splicing GalleryENSG00000080986
Gene ExpressionNDC80 [ NCBI-GEO ]   NDC80 [ EBI - ARRAY_EXPRESS ]   NDC80 [ SEEK ]   NDC80 [ MEM ]
Gene Expression Viewer (FireBrowse)NDC80 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10403
GTEX Portal (Tissue expression)NDC80
Human Protein AtlasENSG00000080986-NDC80 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14777   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO14777  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO14777
Splice isoforms : SwissVarO14777
PhosPhoSitePlusO14777
Domains : Interpro (EBI)Kinetochore_Ndc80   
Domain families : Pfam (Sanger)Ndc80_HEC (PF03801)   
Domain families : Pfam (NCBI)pfam03801   
Conserved Domain (NCBI)NDC80
DMDM Disease mutations10403
Blocks (Seattle)NDC80
PDB (SRS)2IGP    2VE7    3IZ0   
PDB (PDBSum)2IGP    2VE7    3IZ0   
PDB (IMB)2IGP    2VE7    3IZ0   
PDB (RSDB)2IGP    2VE7    3IZ0   
Structural Biology KnowledgeBase2IGP    2VE7    3IZ0   
SCOP (Structural Classification of Proteins)2IGP    2VE7    3IZ0   
CATH (Classification of proteins structures)2IGP    2VE7    3IZ0   
SuperfamilyO14777
Human Protein Atlas [tissue]ENSG00000080986-NDC80 [tissue]
Peptide AtlasO14777
HPRD06277
IPIIPI00005791   IPI00643791   
Protein Interaction databases
DIP (DOE-UCLA)O14777
IntAct (EBI)O14777
FunCoupENSG00000080986
BioGRIDNDC80
STRING (EMBL)NDC80
ZODIACNDC80
Ontologies - Pathways
QuickGOO14777
Ontology : AmiGOmitotic sister chromatid segregation  establishment of mitotic spindle orientation  mitotic cell cycle  chromosome, centromeric region  kinetochore  condensed chromosome kinetochore  condensed nuclear chromosome outer kinetochore  structural constituent of cytoskeleton  protein binding  nucleus  nucleoplasm  centrosome  cytosol  mitotic spindle organization  chromosome segregation  sister chromatid cohesion  attachment of spindle microtubules to kinetochore  membrane  Ndc80 complex  identical protein binding  cell division  metaphase plate congression  attachment of mitotic spindle microtubules to kinetochore  kinetochore organization  positive regulation of mitotic cell cycle spindle assembly checkpoint  positive regulation of protein localization to kinetochore  
Ontology : EGO-EBImitotic sister chromatid segregation  establishment of mitotic spindle orientation  mitotic cell cycle  chromosome, centromeric region  kinetochore  condensed chromosome kinetochore  condensed nuclear chromosome outer kinetochore  structural constituent of cytoskeleton  protein binding  nucleus  nucleoplasm  centrosome  cytosol  mitotic spindle organization  chromosome segregation  sister chromatid cohesion  attachment of spindle microtubules to kinetochore  membrane  Ndc80 complex  identical protein binding  cell division  metaphase plate congression  attachment of mitotic spindle microtubules to kinetochore  kinetochore organization  positive regulation of mitotic cell cycle spindle assembly checkpoint  positive regulation of protein localization to kinetochore  
REACTOMEO14777 [protein]
REACTOME PathwaysR-HSA-68877 [pathway]   
NDEx NetworkNDC80
Atlas of Cancer Signalling NetworkNDC80
Wikipedia pathwaysNDC80
Orthology - Evolution
OrthoDB10403
GeneTree (enSembl)ENSG00000080986
Phylogenetic Trees/Animal Genes : TreeFamNDC80
HOVERGENO14777
HOGENOMO14777
Homologs : HomoloGeneNDC80
Homology/Alignments : Family Browser (UCSC)NDC80
Gene fusions - Rearrangements
Fusion : MitelmanNDC80/TTC39C [18p11.32/18q11.2]  
Fusion : MitelmanSMCHD1/NDC80 [18p11.32/18p11.32]  [t(18;18)(p11;p11)]  
Fusion: TCGA_MDACCNDC80 18p11.32 TTC39C 18q11.2 LUAD
Fusion: TCGA_MDACCSMCHD1 18p11.32 NDC80 18p11.32 LUAD
Tumor Fusion PortalNDC80
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNDC80 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NDC80
dbVarNDC80
ClinVarNDC80
1000_GenomesNDC80 
Exome Variant ServerNDC80
ExAC (Exome Aggregation Consortium)ENSG00000080986
GNOMAD BrowserENSG00000080986
Genetic variants : HAPMAP10403
Genomic Variants (DGV)NDC80 [DGVbeta]
DECIPHERNDC80 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisNDC80 
Mutations
ICGC Data PortalNDC80 
TCGA Data PortalNDC80 
Broad Tumor PortalNDC80
OASIS PortalNDC80 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICNDC80  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDNDC80
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch NDC80
DgiDB (Drug Gene Interaction Database)NDC80
DoCM (Curated mutations)NDC80 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NDC80 (select a term)
intoGenNDC80
NCG5 (London)NDC80
Cancer3DNDC80(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607272   
Orphanet
DisGeNETNDC80
MedgenNDC80
Genetic Testing Registry NDC80
NextProtO14777 [Medical]
TSGene10403
GENETestsNDC80
Target ValidationNDC80
Huge Navigator NDC80 [HugePedia]
snp3D : Map Gene to Disease10403
BioCentury BCIQNDC80
ClinGenNDC80
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10403
Chemical/Pharm GKB GenePA162397359
Clinical trialNDC80
Miscellaneous
canSAR (ICR)NDC80 (select the gene name)
Probes
Litterature
PubMed98 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineNDC80
EVEXNDC80
GoPubMedNDC80
iHOPNDC80
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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