ID NDC80_HUMAN Reviewed; 642 AA. AC O14777; Q6PJX2; DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 193. DE RecName: Full=Kinetochore protein NDC80 homolog; DE AltName: Full=Highly expressed in cancer protein; DE AltName: Full=Kinetochore protein Hec1; DE Short=HsHec1; DE AltName: Full=Kinetochore-associated protein 2; DE AltName: Full=Retinoblastoma-associated protein HEC; GN Name=NDC80; Synonyms=HEC, HEC1, KNTC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND RP DEVELOPMENTAL STAGE. RX PubMed=9315664; DOI=10.1128/mcb.17.10.6049; RA Chen Y., Riley D.J., Chen P.-L., Lee W.-H.; RT "HEC, a novel nuclear protein rich in leucine heptad repeats specifically RT involved in mitosis."; RL Mol. Cell. Biol. 17:6049-6056(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP INTERACTION WITH NEK2; PSMC2; PSMC5 AND SMC1A, SUBCELLULAR LOCATION, AND RP DEVELOPMENTAL STAGE. RX PubMed=9295362; DOI=10.1074/jbc.272.38.24081; RA Chen Y., Sharp Z.D., Lee W.-H.; RT "HEC binds to the seventh regulatory subunit of the 26 S proteasome and RT modulates the proteolysis of mitotic cyclins."; RL J. Biol. Chem. 272:24081-24087(1997). RN [4] RP INTERACTION WITH NEK2; PSMC2; PSMC5; RB1 AND SMC1A. RX PubMed=10409732; DOI=10.1128/mcb.19.8.5417; RA Zheng L., Chen Y., Lee W.-H.; RT "Hec1p, an evolutionarily conserved coiled-coil protein, modulates RT chromosome segregation through interaction with SMC proteins."; RL Mol. Cell. Biol. 19:5417-5428(1999). RN [5] RP INTERACTION WITH RB1 AND SMC1A, AND MUTAGENESIS OF GLU-234. RX PubMed=10779342; DOI=10.1128/mcb.20.10.3529-3537.2000; RA Zheng L., Chen Y., Riley D.J., Chen P.-L., Lee W.-H.; RT "Retinoblastoma protein enhances the fidelity of chromosome segregation RT mediated by hsHec1p."; RL Mol. Cell. Biol. 20:3529-3537(2000). RN [6] RP INTERACTION WITH NEK2, AND PHOSPHORYLATION AT SER-165 BY NEK2. RX PubMed=12386167; DOI=10.1074/jbc.m207069200; RA Chen Y., Riley D.J., Zheng L., Chen P.-L., Lee W.-H.; RT "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is RT essential for faithful chromosome segregation."; RL J. Biol. Chem. 277:49408-49416(2002). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12351790; DOI=10.1126/science.1075596; RA Martin-Lluesma S., Stucke V.M., Nigg E.A.; RT "Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment RT of Mad1/Mad2."; RL Science 297:2267-2270(2002). RN [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=14654001; DOI=10.1016/j.cub.2003.10.056; RA DeLuca J.G., Howell B.J., Canman J.C., Hickey J.M., Fang G., Salmon E.D.; RT "Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 RT and Mad2 to kinetochores."; RL Curr. Biol. 13:2103-2109(2003). RN [9] RP FUNCTION. RX PubMed=15235793; DOI=10.1007/s00412-004-0288-2; RA Stucke V.M., Baumann C., Nigg E.A.; RT "Kinetochore localization and microtubule interaction of the human spindle RT checkpoint kinase Mps1."; RL Chromosoma 113:1-15(2004). RN [10] RP FUNCTION. RX PubMed=15062103; DOI=10.1016/j.cub.2004.03.031; RA Joseph J., Liu S.-T., Jablonski S.A., Yen T.J., Dasso M.; RT "The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore RT interactions in vivo."; RL Curr. Biol. 14:611-617(2004). RN [11] RP FUNCTION. RX PubMed=15239953; DOI=10.1016/j.devcel.2004.06.006; RA Meraldi P., Draviam V.M., Sorger P.K.; RT "Timing and checkpoints in the regulation of mitotic progression."; RL Dev. Cell 7:45-60(2004). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=15133482; DOI=10.1038/sj.embor.7400154; RA Steensgaard P., Garre M., Muradore I., Transidico P., Nigg E.A., RA Kitagawa K., Earnshaw W.C., Faretta M., Musacchio A.; RT "Sgt1 is required for human kinetochore assembly."; RL EMBO Rep. 5:626-631(2004). RN [13] RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE RP NDC80 COMPLEX. RX PubMed=14699129; DOI=10.1074/jbc.m310224200; RA Bharadwaj R., Qi W., Yu H.; RT "Identification of two novel components of the human NDC80 kinetochore RT complex."; RL J. Biol. Chem. 279:13076-13085(2004). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=14978040; DOI=10.1074/jbc.m314205200; RA Lou Y., Yao J., Zereshki A., Dou Z., Ahmed K., Wang H., Hu J., Wang Y., RA Yao X.; RT "NEK2A interacts with MAD1 and possibly functions as a novel integrator of RT the spindle checkpoint signaling."; RL J. Biol. Chem. 279:20049-20057(2004). RN [15] RP INTERACTION WITH AURKB AND CDCA1, AND PHOSPHORYLATION BY AURKA AND AURKB. RX PubMed=14602875; DOI=10.1074/mcp.m300072-mcp200; RA Tien A.-C., Lin M.-H., Su L.-J., Hong Y.-R., Cheng T.-S., Lee Y.-C.G., RA Lin W.-J., Still I.H., Huang C.-Y.F.; RT "Identification of the substrates and interaction proteins of aurora RT kinases from a protein-protein interaction model."; RL Mol. Cell. Proteomics 3:93-104(2004). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A COMPLEX WITH RP MIS12. RX PubMed=15502821; DOI=10.1038/ncb1187; RA Obuse C., Iwasaki O., Kiyomitsu T., Goshima G., Toyoda Y., Yanagida M.; RT "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and RT outer kinetochore protein Zwint-1."; RL Nat. Cell Biol. 6:1135-1141(2004). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=15964272; DOI=10.1016/j.cub.2005.05.026; RA Ahonen L.J., Kallio M.J., Daum J.R., Bolton M., Manke I.A., Yaffe M.B., RA Stukenberg P.T., Gorbsky G.J.; RT "Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and RT modulates the association of spindle-checkpoint proteins at kinetochores."; RL Curr. Biol. 15:1078-1089(2005). RN [18] RP CHARACTERIZATION OF THE NDC80 COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=15961401; DOI=10.1074/jbc.m504070200; RA Ciferri C., De Luca J., Monzani S., Ferrari K.J., Ristic D., Wyman C., RA Stark H., Kilmartin J., Salmon E.D., Musacchio A.; RT "Architecture of the human Ndc80-Hec1 complex, a critical constituent of RT the outer kinetochore."; RL J. Biol. Chem. 280:29088-29095(2005). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A COMPLEX WITH RP ZWINT. RX PubMed=15824131; DOI=10.1083/jcb.200411118; RA Kops G.J.P.L., Kim Y., Weaver B.A.A., Mao Y., McLeod I., Yates J.R. III, RA Tagaya M., Cleveland D.W.; RT "ZW10 links mitotic checkpoint signaling to the structural kinetochore."; RL J. Cell Biol. 169:49-60(2005). RN [20] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15548592; DOI=10.1091/mbc.e04-09-0852; RA DeLuca J.G., Dong Y., Hergert P., Strauss J., Hickey J.M., Salmon E.D., RA McEwen B.F.; RT "Hec1 and Nuf2 are core components of the kinetochore outer plate essential RT for organizing microtubule attachment sites."; RL Mol. Biol. Cell 16:519-531(2005). RN [21] RP INTERACTION WITH CENPH. RX PubMed=15713649; DOI=10.1128/mcb.25.5.1958-1970.2005; RA Mikami Y., Hori T., Kimura H., Fukagawa T.; RT "The functional region of CENP-H interacts with the Nuf2 complex that RT localizes to centromere during mitosis."; RL Mol. Cell. Biol. 25:1958-1970(2005). RN [22] RP FUNCTION, INTERACTION WITH ZWINT, SUBCELLULAR LOCATION, AND DEVELOPMENTAL RP STAGE. RX PubMed=16732327; DOI=10.1038/sj.onc.1209687; RA Lin Y.-T., Chen Y., Wu G., Lee W.-H.; RT "Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful RT chromosome segregation and spindle checkpoint control."; RL Oncogene 25:6901-6914(2006). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP FUNCTION. RX PubMed=23085020; DOI=10.1016/j.devcel.2012.09.012; RA Schmidt J.C., Arthanari H., Boeszoermenyi A., Dashkevich N.M., RA Wilson-Kubalek E.M., Monnier N., Markus M., Oberer M., Milligan R.A., RA Bathe M., Wagner G., Grishchuk E.L., Cheeseman I.M.; RT "The kinetochore-bound Ska1 complex tracks depolymerizing microtubules and RT binds to curved protofilaments."; RL Dev. Cell 23:968-980(2012). RN [26] RP INTERACTION WITH CDT1. RX PubMed=22581055; DOI=10.1038/ncb2489; RA Varma D., Chandrasekaran S., Sundin L.J., Reidy K.T., Wan X., Chasse D.A., RA Nevis K.R., DeLuca J.G., Salmon E.D., Cook J.G.; RT "Recruitment of the human Cdt1 replication licensing protein by the loop RT domain of Hec1 is required for stable kinetochore-microtubule attachment."; RL Nat. Cell Biol. 14:593-603(2012). RN [27] RP FUNCTION. RX PubMed=23891108; DOI=10.1016/j.cub.2013.06.040; RA Shrestha R.L., Draviam V.M.; RT "Lateral to end-on conversion of chromosome-microtubule attachment requires RT kinesins CENP-E and MCAK."; RL Curr. Biol. 23:1514-1526(2013). RN [28] RP ERRATUM OF PUBMED:23891108. RA Shrestha R.L., Draviam V.M.; RL Curr. Biol. 23:2440-2441(2013). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-69, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [30] RP FUNCTION. RX PubMed=25743205; DOI=10.1038/ncomms7447; RA Iemura K., Tanaka K.; RT "Chromokinesin Kid and kinetochore kinesin CENP-E differentially support RT chromosome congression without end-on attachment to microtubules."; RL Nat. Commun. 6:6447-6447(2015). RN [31] RP INTERACTION WITH CKAP5. RX PubMed=27156448; DOI=10.1016/j.cell.2016.04.030; RA Miller M.P., Asbury C.L., Biggins S.; RT "A TOG protein confers tension sensitivity to kinetochore-microtubule RT attachments."; RL Cell 165:1428-1439(2016). RN [32] RP FUNCTION, PHOSPHORYLATION AT SER-55 AND SER-62, ACETYLATION AT LYS-53; RP LYS-59 AND LYS-527, AND MUTAGENESIS OF LYS-53 AND LYS-59. RX PubMed=30409912; DOI=10.1074/jbc.ra118.003844; RA Zhao G., Cheng Y., Gui P., Cui M., Liu W., Wang W., Wang X., Ali M., RA Dou Z., Niu L., Liu H., Anderson L., Ruan K., Hong J., Yao X.; RT "Dynamic acetylation of the kinetochore-associated protein HEC1 ensures RT accurate microtubule-kinetochore attachment."; RL J. Biol. Chem. 294:576-592(2019). CC -!- FUNCTION: Acts as a component of the essential kinetochore-associated CC NDC80 complex, which is required for chromosome segregation and spindle CC checkpoint activity (PubMed:9315664, PubMed:12351790, PubMed:14654001, CC PubMed:14699129, PubMed:15062103, PubMed:15235793, PubMed:15239953, CC PubMed:15548592, PubMed:16732327, PubMed:30409912). Required for CC kinetochore integrity and the organization of stable microtubule CC binding sites in the outer plate of the kinetochore (PubMed:15548592, CC PubMed:30409912). The NDC80 complex synergistically enhances the CC affinity of the SKA1 complex for microtubules and may allow the NDC80 CC complex to track depolymerizing microtubules (PubMed:23085020). Plays a CC role in chromosome congression and is essential for the end-on CC attachment of the kinetochores to spindle microtubules CC (PubMed:25743205, PubMed:23891108). {ECO:0000269|PubMed:12351790, CC ECO:0000269|PubMed:14654001, ECO:0000269|PubMed:14699129, CC ECO:0000269|PubMed:15062103, ECO:0000269|PubMed:15235793, CC ECO:0000269|PubMed:15239953, ECO:0000269|PubMed:15548592, CC ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:23085020, CC ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:25743205, CC ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:9315664}. CC -!- SUBUNIT: Component of the NDC80 complex, which consists of NDC80/HEC1, CC CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two CC subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each CC subcomplex is formed by parallel interactions through the coiled-coil CC domains of individual subunits. Formation of a tetrameric complex is CC mediated by interactions between the C-terminal regions of both CC subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions CC of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 CC complex has an elongated rod-like structure with globular domains at CC either end. Interacts with isoform 1 of NEK2 and ZWINT specifically CC during mitosis. Interacts with CENPH and MIS12. May interact with CC AURKB, PSMC2, PSMC5 and SMC1A. May interact with RB1 during G2 phase CC and mitosis. Interacts with CKAP5 (PubMed:27156448). Interacts with CC CDT1; leading to kinetochore localization of CDT1 (PubMed:22581055). CC {ECO:0000269|PubMed:10409732, ECO:0000269|PubMed:10779342, CC ECO:0000269|PubMed:12386167, ECO:0000269|PubMed:14602875, CC ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:15502821, CC ECO:0000269|PubMed:15713649, ECO:0000269|PubMed:15824131, CC ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:22581055, CC ECO:0000269|PubMed:27156448, ECO:0000269|PubMed:9295362}. CC -!- INTERACTION: CC O14777; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-715849, EBI-746752; CC O14777; P18848: ATF4; NbExp=8; IntAct=EBI-715849, EBI-492498; CC O14777; P48047: ATP5PO; NbExp=3; IntAct=EBI-715849, EBI-355815; CC O14777; Q9Y5K8: ATP6V1D; NbExp=3; IntAct=EBI-715849, EBI-2684998; CC O14777; Q8TC20-4: CAGE1; NbExp=3; IntAct=EBI-715849, EBI-11522698; CC O14777; Q9P1Z2: CALCOCO1; NbExp=4; IntAct=EBI-715849, EBI-749920; CC O14777; Q8TD31-3: CCHCR1; NbExp=6; IntAct=EBI-715849, EBI-10175300; CC O14777; P51946: CCNH; NbExp=3; IntAct=EBI-715849, EBI-741406; CC O14777; O75909: CCNK; NbExp=3; IntAct=EBI-715849, EBI-739806; CC O14777; Q9H211: CDT1; NbExp=7; IntAct=EBI-715849, EBI-456953; CC O14777; Q9H3R5: CENPH; NbExp=6; IntAct=EBI-715849, EBI-1003700; CC O14777; Q96MT8-3: CEP63; NbExp=3; IntAct=EBI-715849, EBI-11522539; CC O14777; Q9UBC2-3: EPS15L1; NbExp=3; IntAct=EBI-715849, EBI-11958621; CC O14777; Q8IYI6: EXOC8; NbExp=3; IntAct=EBI-715849, EBI-742102; CC O14777; Q8IZT9: FAM9C; NbExp=3; IntAct=EBI-715849, EBI-2870039; CC O14777; Q08379: GOLGA2; NbExp=3; IntAct=EBI-715849, EBI-618309; CC O14777; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-715849, EBI-2514791; CC O14777; O14964: HGS; NbExp=6; IntAct=EBI-715849, EBI-740220; CC O14777; O75146-2: HIP1R; NbExp=3; IntAct=EBI-715849, EBI-12292427; CC O14777; Q8IY31: IFT20; NbExp=5; IntAct=EBI-715849, EBI-744203; CC O14777; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-715849, EBI-14069005; CC O14777; Q6P597: KLC3; NbExp=3; IntAct=EBI-715849, EBI-1643885; CC O14777; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-715849, EBI-3044087; CC O14777; P04259: KRT6B; NbExp=3; IntAct=EBI-715849, EBI-740907; CC O14777; O95678: KRT75; NbExp=3; IntAct=EBI-715849, EBI-2949715; CC O14777; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-715849, EBI-739832; CC O14777; Q9NPJ6: MED4; NbExp=4; IntAct=EBI-715849, EBI-394607; CC O14777; P55081: MFAP1; NbExp=3; IntAct=EBI-715849, EBI-1048159; CC O14777; O14777: NDC80; NbExp=2; IntAct=EBI-715849, EBI-715849; CC O14777; Q9GZM8: NDEL1; NbExp=4; IntAct=EBI-715849, EBI-928842; CC O14777; Q9BZD4: NUF2; NbExp=14; IntAct=EBI-715849, EBI-724102; CC O14777; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-715849, EBI-1105153; CC O14777; Q6ZNE9: RUFY4; NbExp=7; IntAct=EBI-715849, EBI-10181525; CC O14777; Q86XK3: SFR1; NbExp=3; IntAct=EBI-715849, EBI-1104535; CC O14777; Q96ES7: SGF29; NbExp=7; IntAct=EBI-715849, EBI-743117; CC O14777; Q9HBM1: SPC25; NbExp=12; IntAct=EBI-715849, EBI-999909; CC O14777; O75558: STX11; NbExp=3; IntAct=EBI-715849, EBI-714135; CC O14777; Q9UBB9: TFIP11; NbExp=6; IntAct=EBI-715849, EBI-1105213; CC O14777; Q6I9Y2: THOC7; NbExp=3; IntAct=EBI-715849, EBI-716286; CC O14777; Q15025: TNIP1; NbExp=9; IntAct=EBI-715849, EBI-357849; CC O14777; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-715849, EBI-11952721; CC O14777; Q13625-3: TP53BP2; NbExp=3; IntAct=EBI-715849, EBI-10175039; CC O14777; P33981-1: TTK; NbExp=4; IntAct=EBI-715849, EBI-15986834; CC O14777; P40222: TXLNA; NbExp=7; IntAct=EBI-715849, EBI-359793; CC O14777; Q8N6Y0: USHBP1; NbExp=4; IntAct=EBI-715849, EBI-739895; CC O14777; Q8N1B4: VPS52; NbExp=3; IntAct=EBI-715849, EBI-2799833; CC O14777; Q9Y3C0: WASHC3; NbExp=10; IntAct=EBI-715849, EBI-712969; CC O14777; Q8N720: ZNF655; NbExp=3; IntAct=EBI-715849, EBI-625509; CC O14777; O95229: ZWINT; NbExp=14; IntAct=EBI-715849, EBI-1001132; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9315664}. Chromosome, CC centromere, kinetochore {ECO:0000269|PubMed:14699129}. Note=Localizes CC to kinetochores from late prophase to anaphase (PubMed:14699129). CC Localizes specifically to the outer plate of the kinetochore CC (PubMed:14699129). {ECO:0000269|PubMed:14699129}. CC -!- DEVELOPMENTAL STAGE: Expression peaks in mitosis. CC {ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:9295362, CC ECO:0000269|PubMed:9315664}. CC -!- PTM: Phosphorylation begins in S phase of the cell cycle and peaks in CC mitosis. Phosphorylated by NEK2. Also phosphorylated by AURKA and CC AURKB. {ECO:0000269|PubMed:12386167, ECO:0000269|PubMed:14602875, CC ECO:0000269|PubMed:30409912}. CC -!- PTM: Acetylated at Lys-53 and Lys-59 by KAT5 during mitosis, promoting CC robust kinetochore-microtubule attachment (PubMed:30409912). CC Deacetylated by SIRT1 (PubMed:30409912). {ECO:0000269|PubMed:30409912}. CC -!- SIMILARITY: Belongs to the NDC80/HEC1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF017790; AAB80726.1; -; mRNA. DR EMBL; BC010171; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS11827.1; -. DR RefSeq; NP_006092.1; NM_006101.2. DR PDB; 2IGP; X-ray; 1.80 A; A=81-196. DR PDB; 2VE7; X-ray; 2.88 A; A/B=80-286. DR PDB; 3IZ0; EM; -; C/E=80-286. DR PDB; 8G0P; X-ray; 2.00 A; A=370-509. DR PDBsum; 2IGP; -. DR PDBsum; 2VE7; -. DR PDBsum; 3IZ0; -. DR PDBsum; 8G0P; -. DR AlphaFoldDB; O14777; -. DR EMDB; EMD-2549; -. DR SMR; O14777; -. DR BioGRID; 115675; 329. DR ComplexPortal; CPX-550; Ndc80 complex. DR CORUM; O14777; -. DR DIP; DIP-35100N; -. DR IntAct; O14777; 124. DR MINT; O14777; -. DR STRING; 9606.ENSP00000261597; -. DR ChEMBL; CHEMBL5660; -. DR GlyGen; O14777; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O14777; -. DR PhosphoSitePlus; O14777; -. DR BioMuta; NDC80; -. DR EPD; O14777; -. DR jPOST; O14777; -. DR MassIVE; O14777; -. DR MaxQB; O14777; -. DR PaxDb; 9606-ENSP00000261597; -. DR PeptideAtlas; O14777; -. DR ProteomicsDB; 48231; -. DR Pumba; O14777; -. DR ABCD; O14777; 1 sequenced antibody. DR Antibodypedia; 6039; 505 antibodies from 39 providers. DR DNASU; 10403; -. DR Ensembl; ENST00000261597.9; ENSP00000261597.4; ENSG00000080986.13. DR GeneID; 10403; -. DR KEGG; hsa:10403; -. DR MANE-Select; ENST00000261597.9; ENSP00000261597.4; NM_006101.3; NP_006092.1. DR UCSC; uc002kli.3; human. DR AGR; HGNC:16909; -. DR CTD; 10403; -. DR DisGeNET; 10403; -. DR GeneCards; NDC80; -. DR HGNC; HGNC:16909; NDC80. DR HPA; ENSG00000080986; Tissue enhanced (bone marrow, lymphoid tissue). DR MIM; 607272; gene. DR neXtProt; NX_O14777; -. DR OpenTargets; ENSG00000080986; -. DR PharmGKB; PA162397359; -. DR VEuPathDB; HostDB:ENSG00000080986; -. DR eggNOG; KOG0995; Eukaryota. DR GeneTree; ENSGT00390000018386; -. DR HOGENOM; CLU_012583_2_0_1; -. DR InParanoid; O14777; -. DR OMA; PSHKFQK; -. DR OrthoDB; 25325at2759; -. DR PhylomeDB; O14777; -. DR TreeFam; TF101177; -. DR PathwayCommons; O14777; -. DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal. DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR Reactome; R-HSA-68877; Mitotic Prometaphase. DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation. DR SignaLink; O14777; -. DR SIGNOR; O14777; -. DR BioGRID-ORCS; 10403; 793 hits in 1162 CRISPR screens. DR ChiTaRS; NDC80; human. DR EvolutionaryTrace; O14777; -. DR GeneWiki; NDC80; -. DR GenomeRNAi; 10403; -. DR Pharos; O14777; Tbio. DR PRO; PR:O14777; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; O14777; Protein. DR Bgee; ENSG00000080986; Expressed in ventricular zone and 137 other cell types or tissues. DR ExpressionAtlas; O14777; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0000775; C:chromosome, centromeric region; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0031262; C:Ndc80 complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0000940; C:outer kinetochore; IDA:BHF-UCL. DR GO; GO:0030332; F:cyclin binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0140483; F:kinetochore adaptor activity; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IMP:UniProtKB. DR GO; GO:0051315; P:attachment of mitotic spindle microtubules to kinetochore; IDA:UniProtKB. DR GO; GO:0008608; P:attachment of spindle microtubules to kinetochore; IDA:ComplexPortal. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0051298; P:centrosome duplication; IDA:MGI. DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB. DR GO; GO:0008315; P:G2/MI transition of meiotic cell cycle; IEA:Ensembl. DR GO; GO:0051383; P:kinetochore organization; IEA:Ensembl. DR GO; GO:0051310; P:metaphase chromosome alignment; IDA:MGI. DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc. DR GO; GO:0000070; P:mitotic sister chromatid segregation; TAS:ProtInc. DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; NAS:ComplexPortal. DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB. DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl. DR GO; GO:0014841; P:skeletal muscle satellite cell proliferation; IEA:Ensembl. DR GO; GO:0007057; P:spindle assembly involved in female meiosis I; IEA:Ensembl. DR DisProt; DP01576; -. DR Gene3D; 6.10.250.1950; -; 1. DR Gene3D; 1.10.418.30; Ncd80 complex, Ncd80 subunit; 1. DR IDEAL; IID00184; -. DR InterPro; IPR040967; DUF5595. DR InterPro; IPR005550; Kinetochore_Ndc80. DR InterPro; IPR038273; Ndc80_sf. DR PANTHER; PTHR10643; KINETOCHORE PROTEIN NDC80; 1. DR PANTHER; PTHR10643:SF2; KINETOCHORE PROTEIN NDC80 HOMOLOG; 1. DR Pfam; PF18077; DUF5595; 1. DR Pfam; PF03801; Ndc80_HEC; 1. DR Genevisible; O14777; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell cycle; Cell division; Centromere; KW Chromosome; Coiled coil; Kinetochore; Mitosis; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1..642 FT /note="Kinetochore protein NDC80 homolog" FT /id="PRO_0000249550" FT REGION 1..445 FT /note="Interaction with the N-terminus of CDCA1" FT REGION 1..250 FT /note="Nuclear localization" FT REGION 1..74 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 128..251 FT /note="Interaction with RB1" FT REGION 251..618 FT /note="Interaction with NEK2 and ZWINT" FT /evidence="ECO:0000269|PubMed:16732327" FT REGION 251..431 FT /note="Interaction with SMC1A" FT REGION 361..547 FT /note="Interaction with PSMC2 and SMC1A" FT REGION 446..642 FT /note="Interaction with the C-terminus of CDCA1 and the FT SPBC24-SPBC25 subcomplex" FT COILED 261..403 FT /evidence="ECO:0000255" FT COILED 458..642 FT /evidence="ECO:0000255" FT COMPBIAS 1..51 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 44 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 53 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:30409912" FT MOD_RES 55 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:30409912" FT MOD_RES 59 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:30409912" FT MOD_RES 62 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:30409912" FT MOD_RES 69 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 165 FT /note="Phosphoserine; by NEK2" FT /evidence="ECO:0000269|PubMed:12386167" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9D0F1" FT MOD_RES 527 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:30409912" FT VARIANT 66 FT /note="S -> A (in dbSNP:rs16943490)" FT /id="VAR_027436" FT VARIANT 348 FT /note="E -> D (in dbSNP:rs12456560)" FT /id="VAR_027437" FT VARIANT 605 FT /note="A -> P (in dbSNP:rs9051)" FT /id="VAR_027438" FT MUTAGEN 53 FT /note="K->Q: Mimics acetylation, leading to increased FT kinetochore-microtubule attachment; when associated with FT Q-59." FT /evidence="ECO:0000269|PubMed:30409912" FT MUTAGEN 53 FT /note="K->R: Impaired acetylation, leading to reduced FT kinetochore-microtubule attachment; when associated with FT R-59." FT /evidence="ECO:0000269|PubMed:30409912" FT MUTAGEN 59 FT /note="K->Q: Mimics acetylation, leading to increased FT kinetochore-microtubule attachment; when associated with FT Q-53." FT /evidence="ECO:0000269|PubMed:30409912" FT MUTAGEN 59 FT /note="K->R: Impaired acetylation, leading to reduced FT kinetochore-microtubule attachment; when associated with FT R-53." FT /evidence="ECO:0000269|PubMed:30409912" FT MUTAGEN 234 FT /note="E->K: Abrogates binding to RB1." FT /evidence="ECO:0000269|PubMed:10779342" FT HELIX 89..105 FT /evidence="ECO:0007829|PDB:2IGP" FT TURN 114..117 FT /evidence="ECO:0007829|PDB:2IGP" FT HELIX 122..133 FT /evidence="ECO:0007829|PDB:2IGP" FT TURN 134..136 FT /evidence="ECO:0007829|PDB:2IGP" FT HELIX 147..157 FT /evidence="ECO:0007829|PDB:2IGP" FT HELIX 166..170 FT /evidence="ECO:0007829|PDB:2IGP" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:2IGP" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:2IGP" FT HELIX 178..194 FT /evidence="ECO:0007829|PDB:2IGP" FT HELIX 222..238 FT /evidence="ECO:0007829|PDB:2VE7" FT HELIX 244..258 FT /evidence="ECO:0007829|PDB:2VE7" FT HELIX 264..286 FT /evidence="ECO:0007829|PDB:2VE7" FT HELIX 371..421 FT /evidence="ECO:0007829|PDB:8G0P" FT HELIX 451..453 FT /evidence="ECO:0007829|PDB:8G0P" FT HELIX 454..509 FT /evidence="ECO:0007829|PDB:8G0P" SQ SEQUENCE 642 AA; 73913 MW; 6A82DA4D8B77ECDC CRC64; MKRSSVSSGG AGRLSMQELR SQDVNKQGLY TPQTKEKPTF GKLSINKPTS ERKVSLFGKR TSGHGSRNSQ LGIFSSSEKI KDPRPLNDKA FIQQCIRQLC EFLTENGYAH NVSMKSLQAP SVKDFLKIFT FLYGFLCPSY ELPDTKFEEE VPRIFKDLGY PFALSKSSMY TVGAPHTWPH IVAALVWLID CIKIHTAMKE SSPLFDDGQP WGEETEDGIM HNKLFLDYTI KCYESFMSGA DSFDEMNAEL QSKLKDLFNV DAFKLESLEA KNRALNEQIA RLEQEREKEP NRLESLRKLK ASLQGDVQKY QAYMSNLESH SAILDQKLNG LNEEIARVEL ECETIKQENT RLQNIIDNQK YSVADIERIN HERNELQQTI NKLTKDLEAE QQKLWNEELK YARGKEAIET QLAEYHKLAR KLKLIPKGAE NSKGYDFEIK FNPEAGANCL VKYRAQVYVP LKELLNETEE EINKALNKKM GLEDTLEQLN AMITESKRSV RTLKEEVQKL DDLYQQKIKE AEEEDEKCAS ELESLEKHKH LLESTVNQGL SEAMNELDAV QREYQLVVQT TTEERRKVGN NLQRLLEMVA THVGSVEKHL EEQIAKVDRE YEECMSEDLS ENIKEIRDKY EKKATLIKSS EE //