SPC25_HUMAN
ID SPC25_HUMAN Reviewed; 224 AA.
AC Q9HBM1; A8K4X8; D3DPC0;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Kinetochore protein Spc25;
DE Short=hSpc25;
GN Name=SPC25; Synonyms=SPBC25; ORFNames=AD024;
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, 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].
RC TISSUE=Adrenal gland;
RA Xiao H., Song H., Gao G., Ren S., Chen Z., Han Z.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [8]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE NDC80
RP COMPLEX, AND SUBCELLULAR LOCATION.
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 [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, 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 [11]
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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, 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).
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:14699129, PubMed:14738735). Required for
CC kinetochore integrity and the organization of stable microtubule
CC binding sites in the outer plate of the kinetochore (PubMed:14738735,
CC PubMed:14699129). 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).
CC {ECO:0000269|PubMed:14699129, 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 Q9HBM1; O14964: HGS; NbExp=3; IntAct=EBI-999909, EBI-740220;
CC Q9HBM1; O14777: NDC80; NbExp=12; IntAct=EBI-999909, EBI-715849;
CC Q9HBM1; Q8NBT2: SPC24; NbExp=13; IntAct=EBI-999909, EBI-999900;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:14738735,
CC ECO:0000269|PubMed:15961401}. Note=Localizes to kinetochores from late
CC prophase to anaphase (PubMed:14738735). Localizes specifically to the
CC outer plate of the kinetochore (PubMed:14738735, PubMed:14699129).
CC {ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:14738735}.
CC -!- SIMILARITY: Belongs to the SPC25 family. {ECO:0000305}.
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DR EMBL; AY456388; AAR88652.1; -; mRNA.
DR EMBL; AF225416; AAG09718.1; -; mRNA.
DR EMBL; CR457197; CAG33478.1; -; mRNA.
DR EMBL; AK291093; BAF83782.1; -; mRNA.
DR EMBL; AC069137; AAY24098.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11289.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11290.1; -; Genomic_DNA.
DR EMBL; BC022255; AAH22255.1; -; mRNA.
DR CCDS; CCDS2229.1; -.
DR RefSeq; NP_065726.1; NM_020675.3.
DR PDB; 2VE7; X-ray; 2.88 A; A/B=118-223.
DR PDB; 3IZ0; EM; -; C/E=118-223.
DR PDBsum; 2VE7; -.
DR PDBsum; 3IZ0; -.
DR AlphaFoldDB; Q9HBM1; -.
DR SMR; Q9HBM1; -.
DR BioGRID; 121507; 56.
DR ComplexPortal; CPX-550; Ndc80 complex.
DR CORUM; Q9HBM1; -.
DR DIP; DIP-35753N; -.
DR IntAct; Q9HBM1; 37.
DR MINT; Q9HBM1; -.
DR STRING; 9606.ENSP00000282074; -.
DR CarbonylDB; Q9HBM1; -.
DR iPTMnet; Q9HBM1; -.
DR PhosphoSitePlus; Q9HBM1; -.
DR BioMuta; SPC25; -.
DR DMDM; 74734256; -.
DR EPD; Q9HBM1; -.
DR jPOST; Q9HBM1; -.
DR MassIVE; Q9HBM1; -.
DR MaxQB; Q9HBM1; -.
DR PaxDb; Q9HBM1; -.
DR PeptideAtlas; Q9HBM1; -.
DR PRIDE; Q9HBM1; -.
DR ProteomicsDB; 81577; -.
DR Antibodypedia; 33800; 214 antibodies from 22 providers.
DR DNASU; 57405; -.
DR Ensembl; ENST00000282074.7; ENSP00000282074.2; ENSG00000152253.9.
DR Ensembl; ENST00000611144.4; ENSP00000481354.1; ENSG00000277909.4.
DR Ensembl; ENST00000616584.1; ENSP00000483050.1; ENSG00000277909.4.
DR GeneID; 57405; -.
DR KEGG; hsa:57405; -.
DR MANE-Select; ENST00000282074.7; ENSP00000282074.2; NM_020675.4; NP_065726.1.
DR UCSC; uc002uel.4; human.
DR CTD; 57405; -.
DR DisGeNET; 57405; -.
DR GeneCards; SPC25; -.
DR HGNC; HGNC:24031; SPC25.
DR HPA; ENSG00000152253; Tissue enhanced (lymphoid).
DR MIM; 609395; gene.
DR neXtProt; NX_Q9HBM1; -.
DR OpenTargets; ENSG00000152253; -.
DR PharmGKB; PA162404413; -.
DR VEuPathDB; HostDB:ENSG00000152253; -.
DR eggNOG; KOG4657; Eukaryota.
DR GeneTree; ENSGT00390000002220; -.
DR HOGENOM; CLU_102420_0_0_1; -.
DR InParanoid; Q9HBM1; -.
DR OMA; QGDYEVT; -.
DR OrthoDB; 1460234at2759; -.
DR PhylomeDB; Q9HBM1; -.
DR TreeFam; TF332941; -.
DR PathwayCommons; Q9HBM1; -.
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; Q9HBM1; -.
DR SIGNOR; Q9HBM1; -.
DR BioGRID-ORCS; 57405; 781 hits in 1086 CRISPR screens.
DR ChiTaRS; SPC25; human.
DR EvolutionaryTrace; Q9HBM1; -.
DR GenomeRNAi; 57405; -.
DR Pharos; Q9HBM1; Tbio.
DR PRO; PR:Q9HBM1; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HBM1; protein.
DR Bgee; ENSG00000152253; Expressed in ventricular zone and 102 other tissues.
DR ExpressionAtlas; Q9HBM1; baseline and differential.
DR Genevisible; Q9HBM1; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0031262; C:Ndc80 complex; IDA:UniProtKB.
DR GO; GO:0031617; C:NMS complex; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IMP:UniProtKB.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IC:ComplexPortal.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB.
DR IDEAL; IID00395; -.
DR InterPro; IPR045143; Spc25.
DR InterPro; IPR013255; Spc25_C.
DR PANTHER; PTHR14281; PTHR14281; 1.
DR Pfam; PF08234; Spindle_Spc25; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Centromere; Chromosome;
KW Coiled coil; Kinetochore; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..224
FT /note="Kinetochore protein Spc25"
FT /id="PRO_0000249565"
FT REGION 1..144
FT /note="Interaction with the N-terminus of SPBC24"
FT REGION 1..56
FT /note="Interaction with the NDC80-NUF2 subcomplex"
FT REGION 145..224
FT /note="Interaction with the C-terminus of SPBC24"
FT COILED 61..142
FT /evidence="ECO:0000255"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:2VE7"
FT TURN 126..130
FT /evidence="ECO:0007829|PDB:2VE7"
FT HELIX 131..141
FT /evidence="ECO:0007829|PDB:2VE7"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:2VE7"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:2VE7"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:2VE7"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:2VE7"
FT HELIX 207..214
FT /evidence="ECO:0007829|PDB:2VE7"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:2VE7"
SQ SEQUENCE 224 AA; 26153 MW; 6DED3216794F4512 CRC64;
MVEDELALFD KSINEFWNKF KSTDTSCQMA GLRDTYKDSI KAFAEKLSVK LKEEERMVEM
FLEYQNQISR QNKLIQEKKD NLLKLIAEVK GKKQELEVLT ANIQDLKEEY SRKKETISTA
NKANAERLKR LQKSADLYKD RLGLEIRKIY GEKLQFIFTN IDPKNPESPF MFSLHLNEAR
DYEVSDSAPH LEGLAEFQEN VRKTNNFSAF LANVRKAFTA TVYN
