SKA1_HUMAN
ID SKA1_HUMAN Reviewed; 255 AA.
AC Q96BD8; B2R9Y6; B4E0P4;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Spindle and kinetochore-associated protein 1;
GN Name=SKA1; Synonyms=C18orf24;
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] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-91.
RC TISSUE=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 [2]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [4]
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SKA2.
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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE SKA1 COMPLEX, AND
RP INTERACTION WITH MICROTUBULES; SKA2 AND SKA3.
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 [8]
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 [9]
RP FUNCTION, INTERACTION WITH SKA3 AND MICROTUBULES, AND MUTAGENESIS OF
RP ARG-155; SER-185; ARG-236; SER-242 AND ARG-245.
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).
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:19289083). Affinity for microtubules is
CC synergistically enhanced in the presence of the ndc-80 complex and may
CC allow the ndc-80 complex to track depolymerizing microtubules
CC (PubMed:23085020). In the complex, it mediates the interaction with
CC microtubules (PubMed:19289083, PubMed:23085020).
CC {ECO:0000269|PubMed:17093495, ECO:0000269|PubMed:19289083,
CC ECO:0000269|PubMed:23085020}.
CC -!- SUBUNIT: Component of the SKA1 complex, composed of SKA1, SKA2 and SKA3
CC (PubMed:17093495). Forms a heterodimer with SKA2; the heterodimer
CC interacting with SKA3 (PubMed:17093495, PubMed:19289083,
CC PubMed:23085020). The core SKA1 complex is composed of 2 SKA1-SKA2
CC heterodimers, each heterodimer interacting with a molecule of the SKA3
CC homodimer (PubMed:19289083). The core SKA1 complex associates with
CC microtubules and forms oligomeric assemblies (PubMed:17093495,
CC PubMed:19289083). Interacts with microtubules; the interaction is
CC direct (PubMed:19289083, PubMed:23085020). Interacts with SKA2
CC (PubMed:19289083). Interacts with SKA3 (PubMed:19289083,
CC PubMed:23085020). {ECO:0000269|PubMed:17093495,
CC ECO:0000269|PubMed:19289083, ECO:0000269|PubMed:23085020}.
CC -!- INTERACTION:
CC Q96BD8; Q9UL45: BLOC1S6; NbExp=8; IntAct=EBI-741854, EBI-465781;
CC Q96BD8; A0A1B0GWI1: CCDC196; NbExp=3; IntAct=EBI-741854, EBI-10181422;
CC Q96BD8; Q8IZT9: FAM9C; NbExp=3; IntAct=EBI-741854, EBI-2870039;
CC Q96BD8; P62195: PSMC5; NbExp=7; IntAct=EBI-741854, EBI-357745;
CC Q96BD8; Q8WVK7: SKA2; NbExp=11; IntAct=EBI-741854, EBI-1773994;
CC Q96BD8; Q8IX90: SKA3; NbExp=11; IntAct=EBI-741854, EBI-1773976;
CC Q96BD8; O95295: SNAPIN; NbExp=5; IntAct=EBI-741854, EBI-296723;
CC Q96BD8; A1L4H1: SSC5D; NbExp=3; IntAct=EBI-741854, EBI-10172867;
CC Q96BD8; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-741854, EBI-6872807;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:15561729}. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:17093495}. Note=Localizes to the outer kinetochore
CC and spindle microtubules during mitosis in a NDC80 complex-dependent
CC manner (PubMed:17093495). Localizes to both the mitotic spindle and
CC kinetochore-associated proteins (PubMed:17093495). Associates with
CC kinetochores following microtubule attachment from prometaphase,
CC through mid-anaphase and then vanishes in telophase (PubMed:17093495).
CC {ECO:0000269|PubMed:17093495}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96BD8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96BD8-2; Sequence=VSP_037250;
CC -!- SIMILARITY: Belongs to the SKA1 family. {ECO:0000305}.
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DR EMBL; AK303464; BAG64506.1; -; mRNA.
DR EMBL; AK313968; BAG36683.1; -; mRNA.
DR EMBL; CH471096; EAW62971.1; -; Genomic_DNA.
DR EMBL; BC015706; AAH15706.1; -; mRNA.
DR CCDS; CCDS11946.1; -. [Q96BD8-1]
DR RefSeq; NP_001034624.1; NM_001039535.2. [Q96BD8-1]
DR RefSeq; NP_659497.1; NM_145060.3. [Q96BD8-1]
DR PDB; 4AJ5; X-ray; 3.32 A; A/B/C/D/E/F/G/H/I/J=1-91.
DR PDB; 4C9Y; X-ray; 2.01 A; A/B=133-255.
DR PDB; 4CA0; X-ray; 2.26 A; A/B=133-255.
DR PDBsum; 4AJ5; -.
DR PDBsum; 4C9Y; -.
DR PDBsum; 4CA0; -.
DR AlphaFoldDB; Q96BD8; -.
DR SMR; Q96BD8; -.
DR BioGRID; 128632; 72.
DR ComplexPortal; CPX-5642; Kinetochore SKA complex.
DR IntAct; Q96BD8; 49.
DR MINT; Q96BD8; -.
DR STRING; 9606.ENSP00000285116; -.
DR iPTMnet; Q96BD8; -.
DR PhosphoSitePlus; Q96BD8; -.
DR BioMuta; SKA1; -.
DR DMDM; 74731226; -.
DR EPD; Q96BD8; -.
DR jPOST; Q96BD8; -.
DR MassIVE; Q96BD8; -.
DR MaxQB; Q96BD8; -.
DR PaxDb; Q96BD8; -.
DR PeptideAtlas; Q96BD8; -.
DR PRIDE; Q96BD8; -.
DR ProteomicsDB; 76069; -. [Q96BD8-1]
DR ProteomicsDB; 76070; -. [Q96BD8-2]
DR Antibodypedia; 22703; 103 antibodies from 23 providers.
DR DNASU; 220134; -.
DR Ensembl; ENST00000285116.8; ENSP00000285116.3; ENSG00000154839.10. [Q96BD8-1]
DR Ensembl; ENST00000398452.6; ENSP00000381470.1; ENSG00000154839.10. [Q96BD8-1]
DR Ensembl; ENST00000417656.6; ENSP00000397222.1; ENSG00000154839.10. [Q96BD8-2]
DR Ensembl; ENST00000571751.5; ENSP00000458992.1; ENSG00000262634.5. [Q96BD8-1]
DR Ensembl; ENST00000616604.2; ENSP00000478259.1; ENSG00000262634.5. [Q96BD8-1]
DR Ensembl; ENST00000633940.1; ENSP00000488815.1; ENSG00000262634.5. [Q96BD8-2]
DR GeneID; 220134; -.
DR KEGG; hsa:220134; -.
DR MANE-Select; ENST00000285116.8; ENSP00000285116.3; NM_145060.4; NP_659497.1.
DR UCSC; uc002let.4; human. [Q96BD8-1]
DR CTD; 220134; -.
DR DisGeNET; 220134; -.
DR GeneCards; SKA1; -.
DR HGNC; HGNC:28109; SKA1.
DR HPA; ENSG00000154839; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 616673; gene.
DR neXtProt; NX_Q96BD8; -.
DR OpenTargets; ENSG00000154839; -.
DR PharmGKB; PA165429102; -.
DR VEuPathDB; HostDB:ENSG00000154839; -.
DR eggNOG; KOG4832; Eukaryota.
DR GeneTree; ENSGT00390000011654; -.
DR HOGENOM; CLU_096842_0_0_1; -.
DR InParanoid; Q96BD8; -.
DR OMA; YQEQTNH; -.
DR PhylomeDB; Q96BD8; -.
DR TreeFam; TF324442; -.
DR PathwayCommons; Q96BD8; -.
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; Q96BD8; -.
DR SIGNOR; Q96BD8; -.
DR BioGRID-ORCS; 220134; 463 hits in 1092 CRISPR screens.
DR ChiTaRS; SKA1; human.
DR GenomeRNAi; 220134; -.
DR Pharos; Q96BD8; Tbio.
DR PRO; PR:Q96BD8; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q96BD8; protein.
DR Bgee; ENSG00000154839; Expressed in ventricular zone and 93 other tissues.
DR ExpressionAtlas; Q96BD8; baseline and differential.
DR Genevisible; Q96BD8; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IPI:ComplexPortal.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0072686; C:mitotic spindle; IBA:GO_Central.
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 Gene3D; 1.10.10.1890; -; 1.
DR InterPro; IPR009829; SKA1.
DR InterPro; IPR042031; SKA1-MBD.
DR PANTHER; PTHR28573; PTHR28573; 1.
DR Pfam; PF07160; SKA1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Centromere; Chromosome; Coiled coil; Cytoplasm; Cytoskeleton; Kinetochore;
KW Microtubule; Mitosis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..255
FT /note="Spindle and kinetochore-associated protein 1"
FT /id="PRO_0000273155"
FT REGION 106..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..255
FT /note="Microtubule binding"
FT /evidence="ECO:0000269|PubMed:23085020"
FT COILED 49..91
FT /evidence="ECO:0000255"
FT COMPBIAS 110..131
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT VAR_SEQ 104..150
FT /note="CVKGSDLDPEEPIKVEEPEPVKKPPKEQRSIKEMPFITCDEFNGVPS -> W
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037250"
FT VARIANT 91
FT /note="V -> I (in dbSNP:rs6507992)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_030091"
FT MUTAGEN 155
FT /note="R->A: Abolishes microtubule binding; when associated
FT with A-236 and A-245."
FT /evidence="ECO:0000269|PubMed:23085020"
FT MUTAGEN 185
FT /note="S->D: Phosphomimetic mutant which strongly reduces
FT microtubule binding; when associated with D-242."
FT /evidence="ECO:0000269|PubMed:23085020"
FT MUTAGEN 236
FT /note="R->A: Abolishes microtubule binding; when associated
FT with A-155 and A-245."
FT /evidence="ECO:0000269|PubMed:23085020"
FT MUTAGEN 242
FT /note="S->D: Phosphomimetic mutant which strongly reduces
FT microtubule binding; when associated with D-185."
FT /evidence="ECO:0000269|PubMed:23085020"
FT MUTAGEN 245
FT /note="R->A: Abolishes microtubule binding; when associated
FT with A-155 and A-236."
FT /evidence="ECO:0000269|PubMed:23085020"
FT HELIX 5..31
FT /evidence="ECO:0007829|PDB:4AJ5"
FT HELIX 33..79
FT /evidence="ECO:0007829|PDB:4AJ5"
FT HELIX 82..88
FT /evidence="ECO:0007829|PDB:4AJ5"
FT HELIX 142..146
FT /evidence="ECO:0007829|PDB:4C9Y"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:4C9Y"
FT HELIX 158..179
FT /evidence="ECO:0007829|PDB:4C9Y"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:4C9Y"
FT HELIX 188..200
FT /evidence="ECO:0007829|PDB:4C9Y"
FT TURN 203..207
FT /evidence="ECO:0007829|PDB:4C9Y"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:4CA0"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:4C9Y"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:4C9Y"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:4C9Y"
FT STRAND 251..254
FT /evidence="ECO:0007829|PDB:4C9Y"
SQ SEQUENCE 255 AA; 29484 MW; 40F578B0B6D9B64D CRC64;
MASSDLEQLC SHVNEKIGNI KKTLSLRNCG QEPTLKTVLN KIGDEIIVIN ELLNKLELEI
QYQEQTNNSL KELCESLEED YKDIEHLKEN VPSHLPQVTV TQSCVKGSDL DPEEPIKVEE
PEPVKKPPKE QRSIKEMPFI TCDEFNGVPS YMKSRLTYNQ INDVIKEINK AVISKYKILH
QPKKSMNSVT RNLYHRFIDE ETKDTKGRYF IVEADIKEFT TLKADKKFHV LLNILRHCRR
LSEVRGGGLT RYVIT
