SPC24_HUMAN
ID SPC24_HUMAN Reviewed; 197 AA.
AC Q8NBT2; B4DZZ7; C9JGC4;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Kinetochore protein Spc24;
DE Short=hSpc24;
GN Name=SPC24; Synonyms=SPBC24;
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] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14738735; DOI=10.1016/j.cub.2003.12.058;
RA McCleland M.L., Kallio M.J., Barrett-Wilt G.A., Kestner C.A.,
RA Shabanowitz J., Hunt D.F., Gorbsky G.J., Stukenberg P.T.;
RT "The vertebrate Ndc80 complex contains Spc24 and Spc25 homologs, which are
RT required to establish and maintain kinetochore-microtubule attachment.";
RL Curr. Biol. 14:131-137(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retinoblastoma, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE NDC80
RP 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 [7]
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 [8]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15561729; DOI=10.1074/mcp.m400158-mcp200;
RA Sauer G., Koerner R., Hanisch A., Ries A., Nigg E.A., Sillje H.H.W.;
RT "Proteome analysis of the human mitotic spindle.";
RL Mol. Cell. Proteomics 4:35-43(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
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:14738735). Required for kinetochore
CC integrity and the organization of stable microtubule binding sites in
CC the outer plate of the kinetochore (PubMed:14738735). The NDC80 complex
CC synergistically enhances the affinity of the SKA1 complex for
CC microtubules and may allow the NDC80 complex to track depolymerizing
CC microtubules (PubMed:23085020). {ECO:0000269|PubMed:14738735,
CC ECO:0000269|PubMed:23085020}.
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. {ECO:0000269|PubMed:14699129}.
CC -!- INTERACTION:
CC Q8NBT2; Q9HBM1: SPC25; NbExp=13; IntAct=EBI-999900, EBI-999909;
CC Q8NBT2; P51687: SUOX; NbExp=3; IntAct=EBI-999900, EBI-3921347;
CC Q8NBT2; Q9P202: WHRN; NbExp=3; IntAct=EBI-999900, EBI-310886;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14738735,
CC ECO:0000269|PubMed:15561729, ECO:0000269|PubMed:15961401,
CC ECO:0000269|PubMed:15964272}. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:14738735, ECO:0000269|PubMed:15561729,
CC ECO:0000269|PubMed:15961401, ECO:0000269|PubMed:15964272}.
CC Note=Localizes to kinetochores from late prophase to anaphase.
CC Localizes specifically to the outer plate of the kinetochore.
CC {ECO:0000269|PubMed:14738735}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NBT2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NBT2-2; Sequence=VSP_054243;
CC -!- SIMILARITY: Belongs to the SPC24 family. {ECO:0000305}.
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DR EMBL; AY456387; AAR88651.1; -; mRNA.
DR EMBL; AK075287; BAC11523.1; -; mRNA.
DR EMBL; AK303157; BAG64259.1; -; mRNA.
DR EMBL; AC011485; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105037; AAI05038.1; -; mRNA.
DR EMBL; BC105039; AAI05040.1; -; mRNA.
DR CCDS; CCDS45974.1; -. [Q8NBT2-1]
DR RefSeq; NP_001303960.1; NM_001317031.1.
DR RefSeq; NP_001303962.1; NM_001317033.1.
DR RefSeq; NP_872319.1; NM_182513.3.
DR RefSeq; XP_005259810.1; XM_005259753.3. [Q8NBT2-2]
DR PDB; 2VE7; X-ray; 2.88 A; C/D=122-197.
DR PDB; 3IZ0; EM; 8.60 A; D/F=122-197.
DR PDBsum; 2VE7; -.
DR PDBsum; 3IZ0; -.
DR AlphaFoldDB; Q8NBT2; -.
DR BioGRID; 127093; 76.
DR ComplexPortal; CPX-550; Ndc80 complex.
DR CORUM; Q8NBT2; -.
DR DIP; DIP-35754N; -.
DR IntAct; Q8NBT2; 44.
DR MINT; Q8NBT2; -.
DR STRING; 9606.ENSP00000465075; -.
DR iPTMnet; Q8NBT2; -.
DR PhosphoSitePlus; Q8NBT2; -.
DR BioMuta; SPC24; -.
DR DMDM; 391358156; -.
DR EPD; Q8NBT2; -.
DR jPOST; Q8NBT2; -.
DR MassIVE; Q8NBT2; -.
DR MaxQB; Q8NBT2; -.
DR PaxDb; Q8NBT2; -.
DR PeptideAtlas; Q8NBT2; -.
DR PRIDE; Q8NBT2; -.
DR ProteomicsDB; 72820; -. [Q8NBT2-1]
DR TopDownProteomics; Q8NBT2-1; -. [Q8NBT2-1]
DR Antibodypedia; 53808; 76 antibodies from 17 providers.
DR DNASU; 147841; -.
DR Ensembl; ENST00000592540.6; ENSP00000465075.1; ENSG00000161888.12. [Q8NBT2-1]
DR GeneID; 147841; -.
DR KEGG; hsa:147841; -.
DR MANE-Select; ENST00000592540.6; ENSP00000465075.1; NM_182513.4; NP_872319.1.
DR UCSC; uc002mql.3; human. [Q8NBT2-1]
DR CTD; 147841; -.
DR DisGeNET; 147841; -.
DR GeneCards; SPC24; -.
DR HGNC; HGNC:26913; SPC24.
DR HPA; ENSG00000161888; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 609394; gene.
DR neXtProt; NX_Q8NBT2; -.
DR OpenTargets; ENSG00000161888; -.
DR PharmGKB; PA162404412; -.
DR VEuPathDB; HostDB:ENSG00000161888; -.
DR eggNOG; ENOG502S26V; Eukaryota.
DR GeneTree; ENSGT00390000005584; -.
DR HOGENOM; CLU_119584_0_0_1; -.
DR InParanoid; Q8NBT2; -.
DR OrthoDB; 1602618at2759; -.
DR PathwayCommons; Q8NBT2; -.
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; Q8NBT2; -.
DR SIGNOR; Q8NBT2; -.
DR BioGRID-ORCS; 147841; 810 hits in 1092 CRISPR screens.
DR ChiTaRS; SPC24; human.
DR EvolutionaryTrace; Q8NBT2; -.
DR GeneWiki; SPC24; -.
DR GenomeRNAi; 147841; -.
DR Pharos; Q8NBT2; Tbio.
DR PRO; PR:Q8NBT2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8NBT2; protein.
DR Bgee; ENSG00000161888; Expressed in ventricular zone and 111 other tissues.
DR ExpressionAtlas; Q8NBT2; baseline and differential.
DR Genevisible; Q8NBT2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:ComplexPortal.
DR GO; GO:0031262; C:Ndc80 complex; IDA:UniProtKB.
DR GO; GO:0031617; C:NMS complex; IC:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IC:ComplexPortal.
DR IDEAL; IID00388; -.
DR InterPro; IPR013252; Ndc80_Spc24.
DR PANTHER; PTHR22142; PTHR22142; 1.
DR Pfam; PF08286; Spc24; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Centromere;
KW Chromosome; Coiled coil; Kinetochore; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..197
FT /note="Kinetochore protein Spc24"
FT /id="PRO_0000249559"
FT REGION 1..131
FT /note="Interaction with the N-terminus of SPBC25"
FT REGION 1..69
FT /note="Interaction with the NDC80-CDCA1 subcomplex"
FT REGION 132..197
FT /note="Interaction with the C-terminus of SPBC25"
FT COILED 33..131
FT /evidence="ECO:0000255"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 72..117
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054243"
FT HELIX 127..131
FT /evidence="ECO:0007829|PDB:2VE7"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:2VE7"
FT HELIX 137..147
FT /evidence="ECO:0007829|PDB:2VE7"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:2VE7"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:2VE7"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:2VE7"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:2VE7"
SQ SEQUENCE 197 AA; 22443 MW; C881496CA428FBDD CRC64;
MAAFRDIEEV SQGLLSLLGA NRAEAQQRRL LGRHEQVVER LLETQDGAEK QLREILTMEK
EVAQSLLNAK EQVHQGGVEL QQLEAGLQEA GEEDTRLKAS LLQLTRELEE LKEIEADLER
QEKEVDEDTT VTIPSAVYVA QLYHQVSKIE WDYECEPGMV KGIHHGPSVA QPIHLDSTQL
SRKFISDYLW SLVDTEW
