ID:NDC80_HUMAN DESCRIPTION: RecName: Full=Kinetochore protein NDC80 homolog; AltName: Full=Highly expressed in cancer protein; AltName: Full=Kinetochore protein Hec1; Short=HsHec1; AltName: Full=Kinetochore-associated protein 2; AltName: Full=Retinoblastoma-associated protein HEC; FUNCTION: Acts as a component of the essential kinetochore- associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. SUBUNIT: Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24- SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C- terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end. Interacts with isoform 1 of NEK2 and ZWINT specifically during mitosis. Interacts with CENPH and MIS12. May interact with AURKB, PSMC2, PSMC5 and SMC1A. May interact with RB1 during G2 phase and mitosis. INTERACTION: Q9H3R5:CENPH; NbExp=3; IntAct=EBI-715849, EBI-1003700; Q9BZD4:NUF2; NbExp=10; IntAct=EBI-715849, EBI-724102; Q9HBM1:SPC25; NbExp=9; IntAct=EBI-715849, EBI-999909; O95229:ZWINT; NbExp=11; IntAct=EBI-715849, EBI-1001132; SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore. Note=Localizes to kinetochores from late prophase to anaphase. Localizes specifically to the outer plate of the kinetochore. DEVELOPMENTAL STAGE: Expression peaks in mitosis. PTM: Phosphorylation begins in S phase of the cell cycle and peaks in mitosis. Phosphorylated by NEK2. May also be phosphorylated by AURKA and AURKB. SIMILARITY: Belongs to the NDC80/HEC1 family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14777
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC005239 - Homo sapiens NDC80 homolog, kinetochore complex component (S. cerevisiae), mRNA (cDNA clone IMAGE:3997364), partial cds. AK289396 - Homo sapiens cDNA FLJ77925 complete cds, highly similar to Homo sapiens kinetochore associated 2, mRNA. AK313184 - Homo sapiens cDNA, FLJ93683, Homo sapiens kinetochore associated 2 (KNTC2), mRNA. BC035617 - Homo sapiens NDC80 homolog, kinetochore complex component (S. cerevisiae), mRNA (cDNA clone MGC:45222 IMAGE:5164424), complete cds. BC010171 - Homo sapiens NDC80 homolog, kinetochore complex component (S. cerevisiae), mRNA (cDNA clone IMAGE:3677694). AF017790 - Homo sapiens retinoblastoma-associated protein HEC mRNA, complete cds. CU690134 - Synthetic construct Homo sapiens gateway clone IMAGE:100019974 5' read NDC80 mRNA. KJ893026 - Synthetic construct Homo sapiens clone ccsbBroadEn_02420 NDC80 gene, encodes complete protein. AB529174 - Synthetic construct DNA, clone: pF1KB6154, Homo sapiens KNTC2 gene for NDC80 homolog, kinetochore complex component, without stop codon, in Flexi system. DQ890765 - Synthetic construct clone IMAGE:100003395; FLH165777.01X; RZPDo839G07160D kinetochore associated 2 (KNTC2) gene, encodes complete protein. DQ893928 - Synthetic construct Homo sapiens clone IMAGE:100008388; FLH165773.01L; RZPDo839G07159D kinetochore associated 2 (KNTC2) gene, encodes complete protein.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O14777 (Reactome details) participates in the following event(s):
R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-68882 Mitotic Anaphase R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-162582 Signal Transduction