NDC80_HUMAN
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 03-AUG-2022, entry version 184.
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}.
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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 PDBsum; 2IGP; -.
DR PDBsum; 2VE7; -.
DR PDBsum; 3IZ0; -.
DR AlphaFoldDB; O14777; -.
DR SMR; O14777; -.
DR BioGRID; 115675; 308.
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; O14777; -.
DR PeptideAtlas; O14777; -.
DR PRIDE; O14777; -.
DR ProteomicsDB; 48231; -.
DR ABCD; O14777; 1 sequenced antibody.
DR Antibodypedia; 6039; 463 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 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; IRFKVHV; -.
DR OrthoDB; 925552at2759; -.
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; 758 hits in 1084 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 135 other tissues.
DR ExpressionAtlas; O14777; baseline and differential.
DR Genevisible; O14777; HS.
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:0031617; C:NMS complex; IC:ComplexPortal.
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: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; IMP:CAFA.
DR GO; GO:0051310; P:metaphase plate congression; 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; IC: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:1905342; P:positive regulation of protein localization to kinetochore; IMP:CAFA.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0007057; P:spindle assembly involved in female meiosis I; IEA:Ensembl.
DR DisProt; DP01576; -.
DR Gene3D; 1.10.418.30; -; 1.
DR IDEAL; IID00184; -.
DR InterPro; IPR040967; DUF5595.
DR InterPro; IPR005550; Kinetochore_Ndc80.
DR InterPro; IPR038273; Ndc80_sf.
DR PANTHER; PTHR10643; PTHR10643; 1.
DR Pfam; PF18077; DUF5595; 1.
DR Pfam; PF03801; Ndc80_HEC; 1.
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 Q-
FT 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 R-
FT 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 Q-
FT 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 R-
FT 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"
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
