KNL1_HUMAN
ID KNL1_HUMAN Reviewed; 2342 AA.
AC Q8NG31; Q8NHE1; Q8WXA6; Q9HCK2; Q9NR92;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Kinetochore scaffold 1;
DE AltName: Full=ALL1-fused gene from chromosome 15q14 protein;
DE Short=AF15q14;
DE AltName: Full=Bub-linking kinetochore protein;
DE Short=Blinkin;
DE AltName: Full=Cancer susceptibility candidate gene 5 protein;
DE AltName: Full=Cancer/testis antigen 29;
DE Short=CT29;
DE AltName: Full=Kinetochore-null protein 1;
DE AltName: Full=Protein CASC5;
DE AltName: Full=Protein D40/AF15q14;
GN Name=KNL1 {ECO:0000312|HGNC:HGNC:24054}; Synonyms=CASC5, KIAA1570;
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] (ISOFORMS 2 AND 4), CHROMOSOMAL TRANSLOCATION
RP WITH KMT2A/MLL1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANTS
RP SER-486; THR-598; GLY-936; GLU-1285 AND ALA-1473.
RX PubMed=10980622; DOI=10.1038/sj.onc.1203789;
RA Hayette S., Tigaud I., Vanier A., Martel S., Corbo L., Charrin C.,
RA Beillard E., Deleage G., Magaud J.-P., Rimokh R.;
RT "AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid
RT leukaemia with a t(11;15)(q23;q14).";
RL Oncogene 19:4446-4450(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND VARIANTS
RP THR-43; ALA-113; SER-486; THR-598 AND GLY-936.
RC TISSUE=Testis;
RX PubMed=12087463; DOI=10.1038/sj.bjc.6600328;
RA Takimoto M., Wei G., Dosaka-Akita H., Mao P., Kondo S., Sakuragi N.,
RA Chiba I., Miura T., Itoh N., Sasao T., Koya R.C., Tsukamoto T.,
RA Fujimoto S., Kato H., Kuzumaki N.;
RT "Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancer
RT of smokers.";
RL Br. J. Cancer 86:1757-1762(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION WITH
RP KMT2A/MLL1, TISSUE SPECIFICITY, AND VARIANTS THR-598 AND GLY-936.
RX PubMed=12618768; DOI=10.1038/sj.onc.1206272;
RA Kuefer M.U., Chinwalla V., Zeleznik-Le N.J., Behm F.G., Naeve C.W.,
RA Rakestraw K.M., Mukatira S.T., Raimondi S.C., Morris S.W.;
RT "Characterization of the MLL partner gene AF15q14 involved in
RT t(11;15)(q23;q14).";
RL Oncogene 22:1418-1424(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 983-2342.
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [6]
RP CHROMOSOMAL TRANSLOCATION WITH KMT2A.
RX PubMed=12618766; DOI=10.1038/sj.onc.1206273;
RA Chinwalla V., Chien A., Odero M., Neilly M.B., Zeleznik-Le N.J.,
RA Rowley J.D.;
RT "A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene
RT MPFYVE on chromosome 15.";
RL Oncogene 22:1400-1410(2003).
RN [7]
RP INTERACTION WITH DSN1 AND MIS12, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP FUNCTION.
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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=15579588; DOI=10.1530/rep.1.00312;
RA Sasao T., Itoh N., Takano H., Watanabe S., Wei G., Tsukamoto T.,
RA Kuzumaki N., Takimoto M.;
RT "The protein encoded by cancer/testis gene D40/AF15q14 is localized in
RT spermatocytes, acrosomes of spermatids and ejaculated spermatozoa.";
RL Reproduction 128:709-716(2004).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BUB1; BUB1B; NSL1;
RP DSN1 AND ZWINT.
RX PubMed=17981135; DOI=10.1016/j.devcel.2007.09.005;
RA Kiyomitsu T., Obuse C., Yanagida M.;
RT "Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic
RT checkpoint through direct interaction with Bub1 and BubR1.";
RL Dev. Cell 13:663-676(2007).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18045986; DOI=10.1091/mbc.e07-10-1051;
RA Cheeseman I.M., Hori T., Fukagawa T., Desai A.;
RT "KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly
RT in vertebrates.";
RL Mol. Biol. Cell 19:587-594(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1076, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-60; SER-1076;
RP SER-1773 AND SER-1845, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=19450515; DOI=10.1016/j.cell.2009.03.035;
RA Wan X., O'Quinn R.P., Pierce H.L., Joglekar A.P., Gall W.E., DeLuca J.G.,
RA Carroll C.W., Liu S.-T., Yen T.J., McEwen B.F., Stukenberg P.T., Desai A.,
RA Salmon E.D.;
RT "Protein architecture of the human kinetochore microtubule attachment
RT site.";
RL Cell 137:672-684(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1076, 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-539; SER-956; SER-1076 AND
RP SER-1831, AND IDENTIFICATION BY 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-60; THR-539; SER-578;
RP SER-584; THR-586; SER-767; SER-956; SER-1039; SER-1076; SER-1088; SER-1448;
RP SER-1675; SER-1845 AND SER-1860, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [17]
RP VARIANT [LARGE SCALE ANALYSIS] THR-598.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
RN [18]
RP VARIANT MCPH4 ILE-2041.
RX PubMed=22983954; DOI=10.1093/hmg/dds386;
RA Genin A., Desir J., Lambert N., Biervliet M., Van Der Aa N., Pierquin G.,
RA Killian A., Tosi M., Urbina M., Lefort A., Libert F., Pirson I.,
RA Abramowicz M.;
RT "Kinetochore KMN network gene CASC5 mutated in primary microcephaly.";
RL Hum. Mol. Genet. 21:5306-5317(2012).
RN [19]
RP VARIANT MCPH4 ILE-2041.
RX PubMed=26626498; DOI=10.1007/s10048-015-0468-7;
RA Saadi A., Verny F., Siquier-Pernet K., Bole-Feysot C., Nitschke P.,
RA Munnich A., Abada-Dendib M., Chaouch M., Abramowicz M., Colleaux L.;
RT "Refining the phenotype associated with CASC5 mutation.";
RL Neurogenetics 17:71-78(2016).
CC -!- FUNCTION: Performs two crucial functions during mitosis: it is
CC essential for spindle-assembly checkpoint signaling and for correct
CC chromosome alignment. Required for attachment of the kinetochores to
CC the spindle microtubules. Directly links BUB1 and BUB1B to
CC kinetochores. Part of the MIS12 complex, which may be fundamental for
CC kinetochore formation and proper chromosome segregation during mitosis.
CC Acts in coordination with CENPK to recruit the NDC80 complex to the
CC outer kinetochore. {ECO:0000269|PubMed:15502821,
CC ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986}.
CC -!- SUBUNIT: Interacts with DSN1, MIS12, BUB1, BUB1B, NSL1 and ZWINT.
CC {ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135}.
CC -!- INTERACTION:
CC Q8NG31; O43683: BUB1; NbExp=2; IntAct=EBI-1001161, EBI-748936;
CC Q8NG31; P62136: PPP1CA; NbExp=2; IntAct=EBI-1001161, EBI-357253;
CC Q8NG31-2; O43683: BUB1; NbExp=3; IntAct=EBI-10973816, EBI-748936;
CC Q8NG31-2; O60566: BUB1B; NbExp=10; IntAct=EBI-10973816, EBI-1001438;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore.
CC Note=Weakly expressed in interphase nuclei. Expression increases from
CC prophase to late anaphase, but greatly diminishes from the telophase
CC and cytokinesis to early G1 phase of cell cycle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8NG31-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NG31-2; Sequence=VSP_013795;
CC Name=3;
CC IsoId=Q8NG31-3; Sequence=VSP_013795, VSP_013796, VSP_013797;
CC Name=4;
CC IsoId=Q8NG31-4; Sequence=VSP_013795, VSP_018524, VSP_018525;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, where it is localized
CC in germ cells, in particular in spermatocytes and in the pre-acrosome
CC of round spermatids. Detected in the acrosome of ejaculated
CC spermatozoa. Detected in adult thymus, bone marrow, colon, small
CC intestine, appendix and placenta, and in fetal liver and thymus.
CC {ECO:0000269|PubMed:10980622, ECO:0000269|PubMed:12087463,
CC ECO:0000269|PubMed:12618768}.
CC -!- DISEASE: Note=A chromosomal aberration involving KNL1 is associated
CC with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14)
CC with KMT2A. May give rise to a KMT2A-KNL1 fusion protein.
CC {ECO:0000269|PubMed:12618766}.
CC -!- DISEASE: Microcephaly 4, primary, autosomal recessive (MCPH4)
CC [MIM:604321]: A disease defined as a head circumference more than 3
CC standard deviations below the age-related mean. Brain weight is
CC markedly reduced and the cerebral cortex is disproportionately small.
CC Despite this marked reduction in size, the gyral pattern is relatively
CC well preserved, with no major abnormality in cortical architecture.
CC Affected individuals are mentally retarded. Primary microcephaly is
CC further defined by the absence of other syndromic features or
CC significant neurological deficits due to degenerative brain disorder.
CC {ECO:0000269|PubMed:22983954, ECO:0000269|PubMed:26626498}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AF15q14ID318.html";
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DR EMBL; AF248041; AAF97513.1; -; mRNA.
DR EMBL; AF461041; AAL67803.1; -; mRNA.
DR EMBL; AB022190; BAC05691.1; -; mRNA.
DR EMBL; AF173994; AAM45143.1; -; mRNA.
DR EMBL; AC022405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB046790; BAB13396.1; -; mRNA.
DR CCDS; CCDS42023.1; -. [Q8NG31-1]
DR CCDS; CCDS42024.1; -. [Q8NG31-2]
DR RefSeq; NP_653091.3; NM_144508.4. [Q8NG31-2]
DR RefSeq; NP_733468.3; NM_170589.4. [Q8NG31-1]
DR PDB; 3SI5; X-ray; 2.20 A; X/Y=234-252.
DR PDB; 4A1G; X-ray; 2.60 A; E/F/G/H=176-226.
DR PDB; 4NF9; X-ray; 2.80 A; A/B=2117-2337.
DR PDB; 4NFA; X-ray; 2.50 A; A=2131-2337.
DR PDBsum; 3SI5; -.
DR PDBsum; 4A1G; -.
DR PDBsum; 4NF9; -.
DR PDBsum; 4NFA; -.
DR AlphaFoldDB; Q8NG31; -.
DR BMRB; Q8NG31; -.
DR SMR; Q8NG31; -.
DR BioGRID; 121354; 100.
DR ComplexPortal; CPX-5644; Kinetochore KNL1 complex.
DR CORUM; Q8NG31; -.
DR DIP; DIP-36474N; -.
DR ELM; Q8NG31; -.
DR IntAct; Q8NG31; 60.
DR MINT; Q8NG31; -.
DR STRING; 9606.ENSP00000335463; -.
DR GlyGen; Q8NG31; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NG31; -.
DR PhosphoSitePlus; Q8NG31; -.
DR BioMuta; KNL1; -.
DR DMDM; 223590239; -.
DR EPD; Q8NG31; -.
DR jPOST; Q8NG31; -.
DR MassIVE; Q8NG31; -.
DR MaxQB; Q8NG31; -.
DR PaxDb; Q8NG31; -.
DR PeptideAtlas; Q8NG31; -.
DR PRIDE; Q8NG31; -.
DR ProteomicsDB; 73413; -. [Q8NG31-1]
DR ProteomicsDB; 73414; -. [Q8NG31-2]
DR ProteomicsDB; 73415; -. [Q8NG31-3]
DR ProteomicsDB; 73416; -. [Q8NG31-4]
DR ABCD; Q8NG31; 1 sequenced antibody.
DR Antibodypedia; 23122; 121 antibodies from 20 providers.
DR CPTC; Q8NG31; 1 antibody.
DR DNASU; 57082; -.
DR Ensembl; ENST00000346991.9; ENSP00000335463.6; ENSG00000137812.21. [Q8NG31-1]
DR Ensembl; ENST00000399668.7; ENSP00000382576.3; ENSG00000137812.21. [Q8NG31-2]
DR GeneID; 57082; -.
DR KEGG; hsa:57082; -.
DR MANE-Select; ENST00000399668.7; ENSP00000382576.3; NM_144508.5; NP_653091.3. [Q8NG31-2]
DR UCSC; uc010bbs.2; human. [Q8NG31-1]
DR CTD; 57082; -.
DR DisGeNET; 57082; -.
DR GeneCards; KNL1; -.
DR HGNC; HGNC:24054; KNL1.
DR HPA; ENSG00000137812; Group enriched (bone marrow, lymphoid tissue, testis).
DR MalaCards; KNL1; -.
DR MIM; 604321; phenotype.
DR MIM; 609173; gene.
DR neXtProt; NX_Q8NG31; -.
DR OpenTargets; ENSG00000137812; -.
DR Orphanet; 2512; Autosomal recessive primary microcephaly.
DR PharmGKB; PA142672201; -.
DR VEuPathDB; HostDB:ENSG00000137812; -.
DR eggNOG; ENOG502QW5H; Eukaryota.
DR GeneTree; ENSGT00410000025918; -.
DR InParanoid; Q8NG31; -.
DR OMA; DINRNLW; -.
DR OrthoDB; 1249457at2759; -.
DR PhylomeDB; Q8NG31; -.
DR TreeFam; TF335517; -.
DR PathwayCommons; Q8NG31; -.
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-606279; Deposition of new CENPA-containing nucleosomes at the centromere.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q8NG31; -.
DR SIGNOR; Q8NG31; -.
DR BioGRID-ORCS; 57082; 577 hits in 1090 CRISPR screens.
DR ChiTaRS; KNL1; human.
DR EvolutionaryTrace; Q8NG31; -.
DR GeneWiki; CASC5; -.
DR GenomeRNAi; 57082; -.
DR Pharos; Q8NG31; Tbio.
DR PRO; PR:Q8NG31; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8NG31; protein.
DR Bgee; ENSG00000137812; Expressed in ventricular zone and 129 other tissues.
DR ExpressionAtlas; Q8NG31; baseline and differential.
DR Genevisible; Q8NG31; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:WormBase.
DR GO; GO:0031617; C:NMS complex; IC:ComplexPortal.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001675; P:acrosome assembly; NAS:UniProtKB.
DR GO; GO:0008608; P:attachment of spindle microtubules to kinetochore; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034501; P:protein localization to kinetochore; IDA:MGI.
DR DisProt; DP01269; -.
DR IDEAL; IID00417; -.
DR InterPro; IPR037388; Blinkin.
DR InterPro; IPR043651; KNL1_MELT_rep.
DR InterPro; IPR040850; Knl1_RWD_C.
DR PANTHER; PTHR16520; PTHR16520; 1.
DR Pfam; PF18210; Knl1_RWD_C; 1.
DR Pfam; PF19221; MELT; 12.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Centromere;
KW Chromosomal rearrangement; Chromosome; Chromosome partition; Coiled coil;
KW Disease variant; Intellectual disability; Kinetochore; Mitosis; Nucleus;
KW Phosphoprotein; Primary microcephaly; Reference proteome; Repeat.
FT CHAIN 1..2342
FT /note="Kinetochore scaffold 1"
FT /id="PRO_0000089327"
FT REPEAT 885..989
FT /note="1"
FT REPEAT 1099..1201
FT /note="2"
FT REGION 1..728
FT /note="Interaction with BUB1 and BUB1B"
FT /evidence="ECO:0000269|PubMed:17981135"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 620..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 855..1201
FT /note="2 X 104 AA approximate repeats"
FT REGION 1639..1662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1834..2316
FT /note="Necessary for kinetochore localization and for
FT interaction with NSL1 and DSN1"
FT /evidence="ECO:0000269|PubMed:17981135"
FT COILED 1942..2133
FT /evidence="ECO:0000255"
FT MOTIF 1789..1803
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 632..646
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1818..1819
FT /note="Breakpoint for translocation to form KMT2A-KNL1"
FT /evidence="ECO:0000269|PubMed:12618766"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 539
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 584
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 586
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 767
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 956
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1039
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1076
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1088
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1675
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1773
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1831
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1845
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1860
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 84..109
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10980622,
FT ECO:0000303|PubMed:12087463"
FT /id="VSP_013795"
FT VAR_SEQ 1764..1772
FT /note="LIETYQKEI -> VGTRRRRYS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12087463"
FT /id="VSP_013796"
FT VAR_SEQ 1773..2342
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12087463"
FT /id="VSP_013797"
FT VAR_SEQ 1819..1859
FT /note="IFDHHTEEDIDKSANSVLIKNLSRTPSSCSSSLDSIKADGT -> VSSVLNQ
FT RMFLNFGFCFVFLNCGYSQILILVSGRQKIIIST (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10980622"
FT /id="VSP_018524"
FT VAR_SEQ 1860..2342
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10980622"
FT /id="VSP_018525"
FT VARIANT 43
FT /note="R -> T (in dbSNP:rs7177192)"
FT /evidence="ECO:0000269|PubMed:12087463"
FT /id="VAR_026428"
FT VARIANT 70
FT /note="T -> A (in dbSNP:rs16970874)"
FT /id="VAR_026429"
FT VARIANT 113
FT /note="T -> A (in dbSNP:rs12911738)"
FT /evidence="ECO:0000269|PubMed:12087463"
FT /id="VAR_026430"
FT VARIANT 177
FT /note="M -> V (in dbSNP:rs35146555)"
FT /id="VAR_061568"
FT VARIANT 486
FT /note="A -> S (in dbSNP:rs2412541)"
FT /evidence="ECO:0000269|PubMed:10980622,
FT ECO:0000269|PubMed:12087463"
FT /id="VAR_026431"
FT VARIANT 598
FT /note="M -> T (in dbSNP:rs11858113)"
FT /evidence="ECO:0000269|PubMed:10980622,
FT ECO:0000269|PubMed:12087463, ECO:0000269|PubMed:12618768,
FT ECO:0000269|PubMed:18987736"
FT /id="VAR_054342"
FT VARIANT 936
FT /note="R -> G (in dbSNP:rs8040502)"
FT /evidence="ECO:0000269|PubMed:10980622,
FT ECO:0000269|PubMed:12087463, ECO:0000269|PubMed:12618768"
FT /id="VAR_026432"
FT VARIANT 1190
FT /note="L -> V (in dbSNP:rs58614880)"
FT /id="VAR_061569"
FT VARIANT 1285
FT /note="K -> E (in dbSNP:rs17747633)"
FT /evidence="ECO:0000269|PubMed:10980622"
FT /id="VAR_026433"
FT VARIANT 1473
FT /note="T -> A (in dbSNP:rs16970911)"
FT /evidence="ECO:0000269|PubMed:10980622"
FT /id="VAR_026434"
FT VARIANT 2041
FT /note="M -> I (in MCPH4; may inactivate an exonic splicing
FT enhancer and result in abnormal splicing;
FT dbSNP:rs763915472)"
FT /evidence="ECO:0000269|PubMed:22983954,
FT ECO:0000269|PubMed:26626498"
FT /id="VAR_069085"
FT VARIANT 2338
FT /note="C -> Y (in dbSNP:rs61164860)"
FT /id="VAR_061570"
FT CONFLICT 37
FT /note="L -> H (in Ref. 3; AAM45143)"
FT /evidence="ECO:0000305"
FT CONFLICT 1332
FT /note="P -> A (in Ref. 2; BAC05691)"
FT /evidence="ECO:0000305"
FT CONFLICT 1357
FT /note="N -> H (in Ref. 2; BAC05691)"
FT /evidence="ECO:0000305"
FT CONFLICT 1756
FT /note="N -> Y (in Ref. 2; BAC05691)"
FT /evidence="ECO:0000305"
FT HELIX 205..211
FT /evidence="ECO:0007829|PDB:4A1G"
FT HELIX 241..250
FT /evidence="ECO:0007829|PDB:3SI5"
FT HELIX 2123..2130
FT /evidence="ECO:0007829|PDB:4NF9"
FT STRAND 2136..2140
FT /evidence="ECO:0007829|PDB:4NFA"
FT STRAND 2146..2151
FT /evidence="ECO:0007829|PDB:4NFA"
FT STRAND 2154..2162
FT /evidence="ECO:0007829|PDB:4NFA"
FT TURN 2168..2170
FT /evidence="ECO:0007829|PDB:4NFA"
FT HELIX 2172..2174
FT /evidence="ECO:0007829|PDB:4NF9"
FT STRAND 2177..2184
FT /evidence="ECO:0007829|PDB:4NFA"
FT TURN 2188..2190
FT /evidence="ECO:0007829|PDB:4NF9"
FT HELIX 2193..2210
FT /evidence="ECO:0007829|PDB:4NFA"
FT TURN 2213..2215
FT /evidence="ECO:0007829|PDB:4NF9"
FT HELIX 2219..2221
FT /evidence="ECO:0007829|PDB:4NF9"
FT HELIX 2222..2249
FT /evidence="ECO:0007829|PDB:4NFA"
FT HELIX 2250..2253
FT /evidence="ECO:0007829|PDB:4NFA"
FT STRAND 2255..2261
FT /evidence="ECO:0007829|PDB:4NFA"
FT STRAND 2264..2271
FT /evidence="ECO:0007829|PDB:4NFA"
FT TURN 2272..2275
FT /evidence="ECO:0007829|PDB:4NFA"
FT STRAND 2276..2283
FT /evidence="ECO:0007829|PDB:4NFA"
FT TURN 2286..2289
FT /evidence="ECO:0007829|PDB:4NFA"
FT STRAND 2295..2302
FT /evidence="ECO:0007829|PDB:4NFA"
FT HELIX 2306..2315
FT /evidence="ECO:0007829|PDB:4NFA"
FT HELIX 2322..2334
FT /evidence="ECO:0007829|PDB:4NFA"
SQ SEQUENCE 2342 AA; 265391 MW; 8E29150CA4F5B5C1 CRC64;
MDGVSSEANE ENDNIERPVR RRHSSILKPP RSPLQDLRGG NERVQESNAL RNKKNSRRVS
FADTIKVFQT ESHMKIVRKS EMEGCSAMVP SQLQLLPPGF KRFSCLSLPE TETGENLLLI
QNKKLEDNYC EITGMNTLLS APIHTQMQQK EFSIIEHTRE RKHANDQTVI FSDENQMDLT
SSHTVMITKG LLDNPISEKS TKIDTTSFLA NLKLHTEDSR MKKEVNFSVD QNTSSENKID
FNDFIKRLKT GKCSAFPDVP DKENFEIPIY SKEPNSASST HQMHVSLKED ENNSNITRLF
REKDDGMNFT QCHTANIQTL IPTSSETNSR ESKGNDITIY GNDFMDLTFN HTLQILPATG
NFSEIENQTQ NAMDVTTGYG TKASGNKTVF KSKQNTAFQD LSINSADKIH ITRSHIMGAE
THIVSQTCNQ DARILAMTPE SIYSNPSIQG CKTVFYSSCN DAMEMTKCLS NMREEKNLLK
HDSNYAKMYC NPDAMSSLTE KTIYSGEENM DITKSHTVAI DNQIFKQDQS NVQIAAAPTP
EKEMMLQNLM TTSEDGKMNV NCNSVPHVSK ERIQQSLSNP LSISLTDRKT ELLSGENMDL
TESHTSNLGS QVPLAAYNLA PESTSESHSQ SKSSSDECEE ITKSRNEPFQ RSDIIAKNSL
TDTWNKDKDW VLKILPYLDK DSPQSADCNQ EIATSHNIVY CGGVLDKQIT NRNTVSWEQS
LFSTTKPLFS SGQFSMKNHD TAISSHTVKS VLGQNSKLAE PLRKSLSNPT PDYCHDKMII
CSEEEQNMDL TKSHTVVIGF GPSELQELGK TNLEHTTGQL TTMNRQIAVK VEKCGKSPIE
KSGVLKSNCI MDVLEDESVQ KPKFPKEKQN VKIWGRKSVG GPKIDKTIVF SEDDKNDMDI
TKSYTIEINH RPLLEKRDCH LVPLAGTSET ILYTCRQDDM EITRSHTTAL ECKTVSPDEI
TTRPMDKTVV FVDNHVELEM TESHTVFIDY QEKERTDRPN FELSQRKSLG TPTVICTPTE
ESVFFPGNGE SDRLVANDSQ LTPLEEWSNN RGPVEVADNM ELSKSATCKN IKDVQSPGFL
NEPLSSKSQR RKSLKLKNDK TIVFSENHKN DMDITQSCMV EIDNESALED KEDFHLAGAS
KTILYSCGQD DMEITRSHTT ALECKTLLPN EIAIRPMDKT VLFTDNYSDL EVTDSHTVFI
DCQATEKILE ENPKFGIGKG KNLGVSFPKD NSCVQEIAEK QALAVGNKIV LHTEQKQQLF
AATNRTTNEI IKFHSAAMDE KVIGKVVDQA CTLEKAQVES CQLNNRDRRN VDFTSSHATA
VCGSSDNYSC LPNVISCTDN LEGSAMLLCD KDEEKANYCP VQNDLAYAND FASEYYLESE
GQPLSAPCPL LEKEEVIQTS TKGQLDCVIT LHKDQDLIKD PRNLLANQTL VYSQDLGEMT
KLNSKRVSFK LPKDQMKVYV DDIYVIPQPH FSTDQPPLPK KGQSSINKEE VILSKAGNKS
LNIIENSSAP ICENKPKILN SEEWFAAACK KELKENIQTT NYNTALDFHS NSDVTKQVIQ
THVNAGEAPD PVITSNVPCF HSIKPNLNNL NGKTGEFLAF QTVHLPPLPE QLLELGNKAH
NDMHIVQATE IHNINIISSN AKDSRDEENK KSHNGAETTS LPPKTVFKDK VRRCSLGIFL
PRLPNKRNCS VTGIDDLEQI PADTTDINHL ETQPVSSKDS GIGSVAGKLN LSPSQYINEE
NLPVYPDEIN SSDSINIETE EKALIETYQK EISPYENKMG KTCNSQKRTW VQEEEDIHKE
KKIRKNEIKF SDTTQDREIF DHHTEEDIDK SANSVLIKNL SRTPSSCSSS LDSIKADGTS
LDFSTYRSSQ MESQFLRDTI CEESLREKLQ DGRITIREFF ILLQVHILIQ KPRQSNLPGN
FTVNTPPTPE DLMLSQYVYR PKIQIYREDC EARRQKIEEL KLSASNQDKL LVDINKNLWE
KMRHCSDKEL KAFGIYLNKI KSCFTKMTKV FTHQGKVALY GKLVQSAQNE REKLQIKIDE
MDKILKKIDN CLTEMETETK NLEDEEKNNP VEEWDSEMRA AEKELEQLKT EEEELQRNLL
ELEVQKEQTL AQIDFMQKQR NRTEELLDQL SLSEWDVVEW SDDQAVFTFV YDTIQLTITF
EESVVGFPFL DKRYRKIVDV NFQSLLDEDQ APPSSLLVHK LIFQYVEEKE SWKKTCTTQH
QLPKMLEEFS LVVHHCRLLG EEIEYLKRWG PNYNLMNIDI NNNELRLLFS SSAAFAKFEI
TLFLSAYYPS VPLPSTIQNH VGNTSQDDIA TILSKVPLEN NYLKNVVKQI YQDLFQDCHF
YH
