SKA2_HUMAN
ID SKA2_HUMAN Reviewed; 121 AA.
AC Q8WVK7; A6NIL3; B3KPL3; E9PCB8;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Spindle and kinetochore-associated protein 2;
DE AltName: Full=Protein FAM33A;
GN Name=SKA2; Synonyms=FAM33A;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, and Lung;
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 FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SKA1.
RX PubMed=17093495; DOI=10.1038/sj.emboj.7601426;
RA Hanisch A., Sillje H.H.W., Nigg E.A.;
RT "Timely anaphase onset requires a novel spindle and kinetochore complex
RT comprising Ska1 and Ska2.";
RL EMBO J. 25:5504-5515(2006).
RN [6]
RP POSSIBLE INTERACTION WITH NR3C1.
RX PubMed=18583474; DOI=10.1677/joe-08-0019;
RA Rice L., Waters C.E., Eccles J., Garside H., Sommer P., Kay P.,
RA Blackhall F.H., Zeef L., Telfer B., Stratford I., Clarke R., Singh D.,
RA Stevens A., White A., Ray D.W.;
RT "Identification and functional analysis of SKA2 interaction with the
RT glucocorticoid receptor.";
RL J. Endocrinol. 198:499-509(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE SKA1 COMPLEX, AND
RP INTERACTION WITH MICROTUBULES AND SKA1.
RX PubMed=19289083; DOI=10.1016/j.devcel.2009.01.011;
RA Welburn J.P.I., Grishchuk E.L., Backer C.B., Wilson-Kubalek E.M.,
RA Yates J.R. III, Cheeseman I.M.;
RT "The human kinetochore Ska1 complex facilitates microtubule
RT depolymerization-coupled motility.";
RL Dev. Cell 16:374-385(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-101, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Component of the SKA1 complex, a microtubule-binding
CC subcomplex of the outer kinetochore that is essential for proper
CC chromosome segregation (PubMed:17093495, PubMed:19289083,
CC PubMed:23085020). Required for timely anaphase onset during mitosis,
CC when chromosomes undergo bipolar attachment on spindle microtubules
CC leading to silencing of the spindle checkpoint (PubMed:17093495). The
CC SKA1 complex is a direct component of the kinetochore-microtubule
CC interface and directly associates with microtubules as oligomeric
CC assemblies (PubMed:19289083). The complex facilitates the processive
CC movement of microspheres along a microtubule in a depolymerization-
CC coupled manner (PubMed:17093495, PubMed:19289083). In the complex, it
CC is required for SKA1 localization (PubMed:19289083). Affinity for
CC microtubules is synergistically enhanced in the presence of the ndc-80
CC complex and may allow the ndc-80 complex to track depolymerizing
CC microtubules (PubMed:23085020). {ECO:0000269|PubMed:17093495,
CC ECO:0000269|PubMed:19289083, ECO:0000269|PubMed:23085020}.
CC -!- SUBUNIT: Component of the SKA1 complex, composed of SKA1, SKA2 and
CC SKA3. Forms a heterodimer with SKA1; the heterodimer interacting with
CC SKA3. The core SKA1 complex is composed of 2 SKA1-SKA2 heterodimers,
CC each heterodimer interacting with a molecule of the SKA3 homodimer. The
CC core SKA1 complex associates with microtubules and forms oligomeric
CC assemblies. Interacts directly with SKA1. Binds directly to
CC microtubules; but with a much lower affinity than SKA1. May interact
CC with NR3C1; the relevance of such interaction remains unclear in vivo.
CC {ECO:0000269|PubMed:17093495, ECO:0000269|PubMed:19289083}.
CC -!- INTERACTION:
CC Q8WVK7; Q9NWB7: IFT57; NbExp=3; IntAct=EBI-1773994, EBI-725672;
CC Q8WVK7; Q53GL6: RALY; NbExp=3; IntAct=EBI-1773994, EBI-9512693;
CC Q8WVK7; Q96BD8: SKA1; NbExp=11; IntAct=EBI-1773994, EBI-741854;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:17093495, ECO:0000269|PubMed:19289083}. Chromosome,
CC centromere, kinetochore {ECO:0000269|PubMed:17093495,
CC ECO:0000269|PubMed:19289083}. Note=Localizes to the outer kinetochore
CC and spindle microtubules during mitosis in a NDC80 complex-dependent
CC manner. Localizes to both the mitotic spindle and kinetochore-
CC associated proteins. {ECO:0000269|PubMed:17093495,
CC ECO:0000269|PubMed:19289083}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WVK7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WVK7-2; Sequence=VSP_047348, VSP_047349;
CC -!- SIMILARITY: Belongs to the SKA2 family. {ECO:0000305}.
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DR EMBL; AK056473; BAG51725.1; -; mRNA.
DR EMBL; AC099850; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94420.1; -; Genomic_DNA.
DR EMBL; BC017873; AAH17873.1; -; mRNA.
DR EMBL; BC106003; AAI06004.1; -; mRNA.
DR EMBL; BI835364; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS45747.1; -. [Q8WVK7-1]
DR CCDS; CCDS45748.1; -. [Q8WVK7-2]
DR RefSeq; NP_001094065.1; NM_001100595.1. [Q8WVK7-2]
DR RefSeq; NP_872426.1; NM_182620.3. [Q8WVK7-1]
DR PDB; 4AJ5; X-ray; 3.32 A; K/L/M/N/O/P/Q/R/S/T=1-121.
DR PDBsum; 4AJ5; -.
DR AlphaFoldDB; Q8WVK7; -.
DR SMR; Q8WVK7; -.
DR BioGRID; 131515; 32.
DR ComplexPortal; CPX-5642; Kinetochore SKA complex.
DR IntAct; Q8WVK7; 15.
DR MINT; Q8WVK7; -.
DR STRING; 9606.ENSP00000333433; -.
DR iPTMnet; Q8WVK7; -.
DR PhosphoSitePlus; Q8WVK7; -.
DR BioMuta; SKA2; -.
DR EPD; Q8WVK7; -.
DR jPOST; Q8WVK7; -.
DR MassIVE; Q8WVK7; -.
DR MaxQB; Q8WVK7; -.
DR PaxDb; Q8WVK7; -.
DR PeptideAtlas; Q8WVK7; -.
DR PRIDE; Q8WVK7; -.
DR ProteomicsDB; 19416; -.
DR ProteomicsDB; 74801; -. [Q8WVK7-1]
DR Antibodypedia; 31070; 138 antibodies from 24 providers.
DR DNASU; 348235; -.
DR Ensembl; ENST00000330137.12; ENSP00000333433.7; ENSG00000182628.13. [Q8WVK7-1]
DR Ensembl; ENST00000437036.6; ENSP00000411231.2; ENSG00000182628.13. [Q8WVK7-2]
DR GeneID; 348235; -.
DR KEGG; hsa:348235; -.
DR MANE-Select; ENST00000330137.12; ENSP00000333433.7; NM_182620.4; NP_872426.1.
DR UCSC; uc002ixd.3; human. [Q8WVK7-1]
DR CTD; 348235; -.
DR DisGeNET; 348235; -.
DR GeneCards; SKA2; -.
DR HGNC; HGNC:28006; SKA2.
DR HPA; ENSG00000182628; Low tissue specificity.
DR MIM; 616674; gene.
DR neXtProt; NX_Q8WVK7; -.
DR OpenTargets; ENSG00000182628; -.
DR PharmGKB; PA165432792; -.
DR VEuPathDB; HostDB:ENSG00000182628; -.
DR eggNOG; ENOG502S6SM; Eukaryota.
DR GeneTree; ENSGT00390000009588; -.
DR HOGENOM; CLU_143881_0_0_1; -.
DR InParanoid; Q8WVK7; -.
DR OMA; MSMEPSA; -.
DR OrthoDB; 1529470at2759; -.
DR PhylomeDB; Q8WVK7; -.
DR TreeFam; TF332958; -.
DR PathwayCommons; Q8WVK7; -.
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; Q8WVK7; -.
DR SIGNOR; Q8WVK7; -.
DR BioGRID-ORCS; 348235; 282 hits in 1087 CRISPR screens.
DR ChiTaRS; SKA2; human.
DR GenomeRNAi; 348235; -.
DR Pharos; Q8WVK7; Tbio.
DR PRO; PR:Q8WVK7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8WVK7; protein.
DR Bgee; ENSG00000182628; Expressed in ventricular zone and 189 other tissues.
DR ExpressionAtlas; Q8WVK7; baseline and differential.
DR Genevisible; Q8WVK7; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IPI:ComplexPortal.
DR GO; GO:0000940; C:outer kinetochore; IDA:UniProtKB.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IMP:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0031110; P:regulation of microtubule polymerization or depolymerization; IDA:UniProtKB.
DR InterPro; IPR026762; Ska2.
DR InterPro; IPR042091; Ska2_N.
DR PANTHER; PTHR32017; PTHR32017; 1.
DR Pfam; PF16740; SKA2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Centromere;
KW Chromosome; Cytoplasm; Cytoskeleton; Kinetochore; Microtubule; Mitosis;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..121
FT /note="Spindle and kinetochore-associated protein 2"
FT /id="PRO_0000266035"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..75
FT /note="MEAEVDKLELMFQKAESDLDYIQYRLEYEIKTNHPDSASEKNPVTLLKELSV
FT IKSRYQTLYARFKPVAVEQKESK -> MASEVGHNLESPETPGGGGWTRVEFPPPAPKG
FT AATVWCLNRLGSRKLSLIWITFNTGWNMKSRLIILIQQVSCHH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047348"
FT VAR_SEQ 76..121
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047349"
FT HELIX 2..32
FT /evidence="ECO:0007829|PDB:4AJ5"
FT HELIX 44..96
FT /evidence="ECO:0007829|PDB:4AJ5"
FT HELIX 104..112
FT /evidence="ECO:0007829|PDB:4AJ5"
SQ SEQUENCE 121 AA; 14188 MW; D079F77E5BD4D7B0 CRC64;
MEAEVDKLEL MFQKAESDLD YIQYRLEYEI KTNHPDSASE KNPVTLLKEL SVIKSRYQTL
YARFKPVAVE QKESKSRICA TVKKTMNMIQ KLQKQTDLEL SPLTKEEKTA AEQFKFHMPD
L
