KANL1_HUMAN
ID KANL1_HUMAN Reviewed; 1105 AA.
AC Q7Z3B3; A8K5E4; B3KT49; I3L4J3; Q6AW85; Q8IYH1; Q9BRH0; Q9NTE7; Q9UFT0;
AC Q9ULF3;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=KAT8 regulatory NSL complex subunit 1;
DE AltName: Full=MLL1/MLL complex subunit KANSL1;
DE AltName: Full=MSL1 homolog 1;
DE Short=hMSL1v1;
DE AltName: Full=NSL complex protein NSL1;
DE AltName: Full=Non-specific lethal 1 homolog;
GN Name=KANSL1; Synonyms=CENP-36, KIAA1267, MSL1V1, NSL1;
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 3), AND VARIANTS
RP PRO-718; LEU-1010 AND THR-1085.
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-1010.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LEU-1010.
RC TISSUE=Fetal kidney, Mammary cancer, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-1010.
RC TISSUE=Leukocyte, and PNS;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=11641718; DOI=10.1007/s00335-001-2044-8;
RA Poorkaj P., Kas A., D'Souza I., Zhou Y., Pham Q., Stone M., Olson M.V.,
RA Schellenberg G.D.;
RT "A genomic sequence analysis of the mouse and human microtubule-associated
RT protein tau.";
RL Mamm. Genome 12:700-712(2001).
RN [7]
RP IDENTIFICATION IN THE MLL1/MLL COMPLEX.
RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031;
RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J.,
RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.;
RT "Physical association and coordinate function of the H3 K4
RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.";
RL Cell 121:873-885(2005).
RN [8]
RP IDENTIFICATION IN A MULTIPROTEIN COMPLEX.
RX PubMed=16227571; DOI=10.1128/mcb.25.21.9175-9188.2005;
RA Smith E.R., Cayrou C., Huang R., Lane W.S., Cote J., Lucchesi J.C.;
RT "A human protein complex homologous to the Drosophila MSL complex is
RT responsible for the majority of histone H4 acetylation at lysine 16.";
RL Mol. Cell. Biol. 25:9175-9188(2005).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP IDENTIFICATION IN THE NSL COMPLEX, AND INTERACTION WITH KAT8.
RX PubMed=16543150; DOI=10.1016/j.molcel.2006.02.007;
RA Mendjan S., Taipale M., Kind J., Holz H., Gebhardt P., Schelder M.,
RA Vermeulen M., Buscaino A., Duncan K., Mueller J., Wilm M.,
RA Stunnenberg H.G., Saumweber H., Akhtar A.;
RT "Nuclear pore components are involved in the transcriptional regulation of
RT dosage compensation in Drosophila.";
RL Mol. Cell 21:811-823(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268; SER-991 AND THR-1003,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249; SER-268 AND SER-1045,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, 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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-104, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=20813266; DOI=10.1016/j.cell.2010.07.047;
RA Ohta S., Bukowski-Wills J.C., Sanchez-Pulido L., Alves Fde L., Wood L.,
RA Chen Z.A., Platani M., Fischer L., Hudson D.F., Ponting C.P., Fukagawa T.,
RA Earnshaw W.C., Rappsilber J.;
RT "The protein composition of mitotic chromosomes determined using
RT multiclassifier combinatorial proteomics.";
RL Cell 142:810-821(2010).
RN [16]
RP FUNCTION IN HISTONE H4 ACETYLATION, IDENTIFICATION IN NSL COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20018852; DOI=10.1074/jbc.c109.087981;
RA Cai Y., Jin J., Swanson S.K., Cole M.D., Choi S.H., Florens L.,
RA Washburn M.P., Conaway J.W., Conaway R.C.;
RT "Subunit composition and substrate specificity of a MOF-containing histone
RT acetyltransferase distinct from the male-specific lethal (MSL) complex.";
RL J. Biol. Chem. 285:4268-4272(2010).
RN [17]
RP INTERACTION WITH KAT8.
RX PubMed=20620954; DOI=10.1016/j.molcel.2010.05.021;
RA Raja S.J., Charapitsa I., Conrad T., Vaquerizas J.M., Gebhardt P., Holz H.,
RA Kadlec J., Fraterman S., Luscombe N.M., Akhtar A.;
RT "The nonspecific lethal complex is a transcriptional regulator in
RT Drosophila.";
RL Mol. Cell 38:827-841(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268; SER-991 AND THR-1003,
RP 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 [19]
RP INTERACTION WITH KAT8, AND MUTAGENESIS OF GLU-910; PHE-917 AND HIS-921.
RX PubMed=21217699; DOI=10.1038/nsmb.1960;
RA Kadlec J., Hallacli E., Lipp M., Holz H., Sanchez-Weatherby J., Cusack S.,
RA Akhtar A.;
RT "Structural basis for MOF and MSL3 recruitment into the dosage compensation
RT complex by MSL1.";
RL Nat. Struct. Mol. Biol. 18:142-149(2011).
RN [20]
RP FUNCTION IN NSL COMPLEX, INTERACTION WITH KAT8, AND MUTAGENESIS OF
RP 852-ARG--ARG-855; 856-GLY--SER-859; 860-PHE--ASN-863; 864-ASN--ILE-867 AND
RP 868-PRO--VAL-871.
RX PubMed=22547026; DOI=10.1038/cr.2012.72;
RA Huang J., Wan B., Wu L., Yang Y., Dou Y., Lei M.;
RT "Structural insight into the regulation of MOF in the male-specific lethal
RT complex and the non-specific lethal complex.";
RL Cell Res. 22:1078-1081(2012).
RN [21]
RP INVOLVEMENT IN KDVS, AND VARIANT KDVS 606-ARG--ARG-1105 DEL.
RX PubMed=22544367; DOI=10.1038/ng.2257;
RA Zollino M., Orteschi D., Murdolo M., Lattante S., Battaglia D.,
RA Stefanini C., Mercuri E., Chiurazzi P., Neri G., Marangi G.;
RT "Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype.";
RL Nat. Genet. 44:636-638(2012).
RN [22]
RP INVOLVEMENT IN KDVS, AND VARIANT KDVS 306-GLN--ARG-1105 DEL.
RX PubMed=22544363; DOI=10.1038/ng.2262;
RA Koolen D.A., Kramer J.M., Neveling K., Nillesen W.M., Moore-Barton H.L.,
RA Elmslie F.V., Toutain A., Amiel J., Malan V., Tsai A.C., Cheung S.W.,
RA Gilissen C., Verwiel E.T., Martens S., Feuth T., Bongers E.M., de Vries P.,
RA Scheffer H., Vissers L.E., de Brouwer A.P., Brunner H.G., Veltman J.A.,
RA Schenck A., Yntema H.G., de Vries B.B.;
RT "Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31
RT microdeletion syndrome.";
RL Nat. Genet. 44:639-641(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249; SER-268; SER-991;
RP SER-994 AND SER-1045, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-262 AND LYS-331, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [26]
RP INVOLVEMENT IN KDVS, AND VARIANT KDVS 348-ARG--ARG-1105 DEL.
RX PubMed=26424144; DOI=10.1136/jmedgenet-2015-103184;
RA Zollino M., Marangi G., Ponzi E., Orteschi D., Ricciardi S., Lattante S.,
RA Murdolo M., Battaglia D., Contaldo I., Mercuri E., Stefanini M.C.,
RA Caumes R., Edery P., Rossi M., Piccione M., Corsello G., Della Monica M.,
RA Scarano F., Priolo M., Gentile M., Zampino G., Vijzelaar R.,
RA Abdulrahman O., Rauch A., Oneda B., Deardorff M.A., Saitta S.C., Falk M.J.,
RA Dubbs H., Zackai E.;
RT "Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening
RT the clinical spectrum and genotype-phenotype correlations in a large cohort
RT of patients.";
RL J. Med. Genet. 52:804-814(2015).
CC -!- FUNCTION: As part of the NSL complex it is involved in acetylation of
CC nucleosomal histone H4 on several lysine residues and therefore may be
CC involved in the regulation of transcription.
CC {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22547026}.
CC -!- SUBUNIT: Component of some MLL1/MLL complex, at least composed of the
CC core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as
CC the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1,
CC LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2,
CC RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and
CC TEX10. Component of the NSL complex at least composed of MOF/KAT8,
CC KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.
CC Interacts with KAT8; the interaction is direct.
CC {ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:16227571,
CC ECO:0000269|PubMed:16543150, ECO:0000269|PubMed:20018852,
CC ECO:0000269|PubMed:20620954, ECO:0000269|PubMed:21217699,
CC ECO:0000269|PubMed:22547026}.
CC -!- INTERACTION:
CC Q7Z3B3; Q13137: CALCOCO2; NbExp=5; IntAct=EBI-740244, EBI-739580;
CC Q7Z3B3; Q96JN2-2: CCDC136; NbExp=3; IntAct=EBI-740244, EBI-10171416;
CC Q7Z3B3; Q15834: CCDC85B; NbExp=2; IntAct=EBI-740244, EBI-739674;
CC Q7Z3B3; Q99459: CDC5L; NbExp=3; IntAct=EBI-740244, EBI-374880;
CC Q7Z3B3; Q01850: CDR2; NbExp=4; IntAct=EBI-740244, EBI-1181367;
CC Q7Z3B3; Q8NHQ1: CEP70; NbExp=4; IntAct=EBI-740244, EBI-739624;
CC Q7Z3B3; Q96EV8: DTNBP1; NbExp=3; IntAct=EBI-740244, EBI-465804;
CC Q7Z3B3; A1L4K1: FSD2; NbExp=3; IntAct=EBI-740244, EBI-5661036;
CC Q7Z3B3; Q08379: GOLGA2; NbExp=4; IntAct=EBI-740244, EBI-618309;
CC Q7Z3B3; Q96ED9: HOOK2; NbExp=4; IntAct=EBI-740244, EBI-743290;
CC Q7Z3B3; Q9BVG8: KIFC3; NbExp=4; IntAct=EBI-740244, EBI-2125614;
CC Q7Z3B3; P19012: KRT15; NbExp=5; IntAct=EBI-740244, EBI-739566;
CC Q7Z3B3; P43365: MAGEA12; NbExp=3; IntAct=EBI-740244, EBI-749530;
CC Q7Z3B3; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-740244, EBI-10172876;
CC Q7Z3B3; P37198: NUP62; NbExp=4; IntAct=EBI-740244, EBI-347978;
CC Q7Z3B3; Q86Y26: NUTM1; NbExp=3; IntAct=EBI-740244, EBI-10178410;
CC Q7Z3B3; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-740244, EBI-302345;
CC Q7Z3B3; Q96R06: SPAG5; NbExp=3; IntAct=EBI-740244, EBI-413317;
CC Q7Z3B3; Q9UBB9: TFIP11; NbExp=5; IntAct=EBI-740244, EBI-1105213;
CC Q7Z3B3; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-740244, EBI-3650647;
CC Q7Z3B3; P14373: TRIM27; NbExp=4; IntAct=EBI-740244, EBI-719493;
CC Q7Z3B3; P61964: WDR5; NbExp=12; IntAct=EBI-740244, EBI-540834;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20018852}. Nucleus.
CC Chromosome, centromere, kinetochore {ECO:0000269|PubMed:20813266}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z3B3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z3B3-2; Sequence=VSP_041132, VSP_041133;
CC Name=3;
CC IsoId=Q7Z3B3-4; Sequence=VSP_041132, VSP_041133, VSP_058944;
CC -!- TISSUE SPECIFICITY: Expressed in the brain.
CC {ECO:0000269|PubMed:11641718}.
CC -!- DISEASE: Koolen-De Vries syndrome (KDVS) [MIM:610443]: An autosomal
CC dominant, multisystem disorder characterized by hypotonia,
CC developmental delay, moderate to severe intellectual disability, and
CC distinctive dysmorphic features including tall, broad forehead, long
CC face, upslanting palpebral fissures, epicanthal folds, tubular nose
CC with bulbous nasal tip, and large ears. Expressive language development
CC is particularly impaired compared with receptive language or motor
CC skills. Additional features include social and friendly behavior,
CC epilepsy, musculoskeletal anomalies, congenital heart defects,
CC urogenital malformations, and ectodermal anomalies.
CC {ECO:0000269|PubMed:22544363, ECO:0000269|PubMed:22544367,
CC ECO:0000269|PubMed:26424144}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH10565.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB033093; BAA86581.1; -; mRNA.
DR EMBL; AK094946; BAG52961.1; -; mRNA.
DR EMBL; AK291259; BAF83948.1; -; mRNA.
DR EMBL; AL117476; CAB55949.1; -; mRNA.
DR EMBL; AL137317; CAB70694.1; -; mRNA.
DR EMBL; BX538006; CAD97958.1; -; mRNA.
DR EMBL; BX648760; CAH10565.1; ALT_INIT; mRNA.
DR EMBL; AC217773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR936218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF495991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035892; AAH35892.1; -; mRNA.
DR EMBL; BC098376; AAH98376.1; -; mRNA.
DR CCDS; CCDS11503.2; -. [Q7Z3B3-1]
DR PIR; T17259; T17259.
DR PIR; T46385; T46385.
DR RefSeq; NP_001180394.1; NM_001193465.1.
DR RefSeq; NP_001180395.1; NM_001193466.1.
DR RefSeq; NP_056258.1; NM_015443.3.
DR RefSeq; XP_006721886.1; XM_006721823.1.
DR RefSeq; XP_006721887.1; XM_006721824.3.
DR PDB; 4CY1; X-ray; 1.50 A; C/D=585-598.
DR PDB; 4CY2; X-ray; 2.00 A; D=585-598.
DR PDBsum; 4CY1; -.
DR PDBsum; 4CY2; -.
DR AlphaFoldDB; Q7Z3B3; -.
DR SMR; Q7Z3B3; -.
DR BioGRID; 129744; 91.
DR ComplexPortal; CPX-809; NSL histone acetyltransferase complex.
DR CORUM; Q7Z3B3; -.
DR ELM; Q7Z3B3; -.
DR IntAct; Q7Z3B3; 54.
DR MINT; Q7Z3B3; -.
DR STRING; 9606.ENSP00000262419; -.
DR iPTMnet; Q7Z3B3; -.
DR PhosphoSitePlus; Q7Z3B3; -.
DR BioMuta; KANSL1; -.
DR DMDM; 334302834; -.
DR EPD; Q7Z3B3; -.
DR jPOST; Q7Z3B3; -.
DR MassIVE; Q7Z3B3; -.
DR MaxQB; Q7Z3B3; -.
DR PaxDb; Q7Z3B3; -.
DR PeptideAtlas; Q7Z3B3; -.
DR PRIDE; Q7Z3B3; -.
DR ProteomicsDB; 47521; -.
DR ProteomicsDB; 69022; -. [Q7Z3B3-1]
DR ProteomicsDB; 69023; -. [Q7Z3B3-2]
DR Antibodypedia; 2016; 78 antibodies from 15 providers.
DR DNASU; 284058; -.
DR Ensembl; ENST00000262419.10; ENSP00000262419.6; ENSG00000120071.15.
DR Ensembl; ENST00000432791.7; ENSP00000387393.3; ENSG00000120071.15.
DR Ensembl; ENST00000572904.6; ENSP00000461484.1; ENSG00000120071.15.
DR Ensembl; ENST00000574590.6; ENSP00000461812.2; ENSG00000120071.15.
DR GeneID; 284058; -.
DR KEGG; hsa:284058; -.
DR UCSC; uc002ikc.4; human. [Q7Z3B3-1]
DR UCSC; uc060gjw.1; human.
DR CTD; 284058; -.
DR DisGeNET; 284058; -.
DR GeneCards; KANSL1; -.
DR GeneReviews; KANSL1; -.
DR HGNC; HGNC:24565; KANSL1.
DR HPA; ENSG00000120071; Low tissue specificity.
DR MalaCards; KANSL1; -.
DR MIM; 610443; phenotype.
DR MIM; 612452; gene.
DR neXtProt; NX_Q7Z3B3; -.
DR Orphanet; 363958; 17q21.31 microdeletion syndrome.
DR Orphanet; 363965; Koolen-De Vries syndrome due to a point mutation.
DR PharmGKB; PA142671604; -.
DR VEuPathDB; HostDB:ENSG00000120071; -.
DR eggNOG; ENOG502QYK7; Eukaryota.
DR InParanoid; Q7Z3B3; -.
DR OrthoDB; 191128at2759; -.
DR PhylomeDB; Q7Z3B3; -.
DR TreeFam; TF336511; -.
DR PathwayCommons; Q7Z3B3; -.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR SignaLink; Q7Z3B3; -.
DR SIGNOR; Q7Z3B3; -.
DR BioGRID-ORCS; 284058; 457 hits in 1089 CRISPR screens.
DR ChiTaRS; KANSL1; human.
DR GeneWiki; KIAA1267; -.
DR GenomeRNAi; 284058; -.
DR Pharos; Q7Z3B3; Tbio.
DR PRO; PR:Q7Z3B3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q7Z3B3; protein.
DR Bgee; ENSG00000120071; Expressed in bone marrow cell and 174 other tissues.
DR ExpressionAtlas; Q7Z3B3; baseline and differential.
DR Genevisible; Q7Z3B3; HS.
DR GO; GO:0000123; C:histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0000776; C:kinetochore; IEA:UniProtKB-KW.
DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB.
DR GO; GO:0044545; C:NSL complex; IDA:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0035035; F:histone acetyltransferase binding; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0043984; P:histone H4-K16 acetylation; IDA:UniProtKB.
DR GO; GO:0043981; P:histone H4-K5 acetylation; IDA:UniProtKB.
DR GO; GO:0043982; P:histone H4-K8 acetylation; IDA:UniProtKB.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:ComplexPortal.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:ComplexPortal.
DR InterPro; IPR026180; NSL1.
DR InterPro; IPR029332; PEHE_dom.
DR PANTHER; PTHR22443; PTHR22443; 1.
DR Pfam; PF15275; PEHE; 1.
DR SMART; SM01300; PEHE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Centromere;
KW Chromatin regulator; Chromosome; Coiled coil; Disease variant;
KW Intellectual disability; Isopeptide bond; Kinetochore; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1105
FT /note="KAT8 regulatory NSL complex subunit 1"
FT /id="PRO_0000234565"
FT REGION 145..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 225..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 399..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 733..857
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..882
FT /note="Required for activation of KAT8 histone
FT acetyltransferase activity"
FT REGION 883..1105
FT /note="Sufficient for interaction with KAT8"
FT REGION 938..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1061..1105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 283..314
FT /evidence="ECO:0000255"
FT COMPBIAS 158..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 782..802
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 821..853
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 938..994
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 104
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 994
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1003
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 1045
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 262
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 331
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..669
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_041132"
FT VAR_SEQ 670..673
FT /note="AFPD -> MFLA (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_041133"
FT VAR_SEQ 735..798
FT /note="KLSHHQTRPDRTHRQHLDDVGAVPMVERVTAPKAERLLNPPPPVHDPNHSKM
FT RLRDHSSERSEV -> M (in isoform 3)"
FT /id="VSP_058944"
FT VARIANT 104
FT /note="K -> T (in dbSNP:rs17585974)"
FT /id="VAR_049515"
FT VARIANT 221
FT /note="T -> I (in dbSNP:rs17662853)"
FT /id="VAR_049516"
FT VARIANT 225
FT /note="N -> D (in dbSNP:rs35643216)"
FT /id="VAR_049517"
FT VARIANT 306..1105
FT /note="Missing (in KDVS)"
FT /evidence="ECO:0000269|PubMed:22544363"
FT /id="VAR_081891"
FT VARIANT 348..1105
FT /note="Missing (in KDVS)"
FT /evidence="ECO:0000269|PubMed:26424144"
FT /id="VAR_081892"
FT VARIANT 606..1105
FT /note="Missing (in KDVS)"
FT /evidence="ECO:0000269|PubMed:22544367"
FT /id="VAR_081893"
FT VARIANT 718
FT /note="S -> P (in dbSNP:rs34043286)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_049518"
FT VARIANT 1010
FT /note="P -> L (in dbSNP:rs7220988)"
FT /evidence="ECO:0000269|PubMed:10574462,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_026287"
FT VARIANT 1085
FT /note="I -> T (in dbSNP:rs34579536)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_049519"
FT MUTAGEN 852..855
FT /note="RRRR->AAAA: Abolishes KAT8 histone acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:22547026"
FT MUTAGEN 856..859
FT /note="GESS->AAAA: Strongly reduces KAT8 histone
FT acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:22547026"
FT MUTAGEN 860..863
FT /note="FDIN->AAAA: Strongly reduces KAT8 histone
FT acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:22547026"
FT MUTAGEN 864..867
FT /note="NIVI->AAAA: Abolishes KAT8 histone acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:22547026"
FT MUTAGEN 868..871
FT /note="PMSV->AAAA: Reduces KAT8 histone acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:22547026"
FT MUTAGEN 910
FT /note="E->R: Abolishes interaction with KAT8."
FT /evidence="ECO:0000269|PubMed:21217699"
FT MUTAGEN 917
FT /note="F->R: No effect on interaction with KAT8."
FT /evidence="ECO:0000269|PubMed:21217699"
FT MUTAGEN 921
FT /note="H->R: Abolishes interaction with KAT8."
FT /evidence="ECO:0000269|PubMed:21217699"
FT CONFLICT 525
FT /note="R -> P (in Ref. 4; KF495991)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="I -> F (in Ref. 3; CAB70694)"
FT /evidence="ECO:0000305"
FT CONFLICT 683
FT /note="S -> G (in Ref. 3; CAH10565)"
FT /evidence="ECO:0000305"
FT CONFLICT 849
FT /note="Missing (in Ref. 2; BAF83948 and 4; KF495991)"
FT /evidence="ECO:0000305"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:4CY1"
SQ SEQUENCE 1105 AA; 121025 MW; B69D11BC522B9CAD CRC64;
MAAMAPALTD AAAEAHHIRF KLAPPSSTLS PGSAENNGNA NILIAANGTK RKAIAAEDPS
LDFRNNPTKE DLGKLQPLVA SYLCSDVTSV PSKESLKLQG VFSKQTVLKS HPLLSQSYEL
RAELLGRQPV LEFSLENLRT MNTSGQTALP QAPVNGLAKK LTKSSTHSDH DNSTSLNGGK
RALTSSALHG GEMGGSESGD LKGGMTNCTL PHRSLDVEHT TLYSNNSTAN KSSVNSMEQP
ALQGSSRLSP GTDSSSNLGG VKLEGKKSPL SSILFSALDS DTRITALLRR QADIESRARR
LQKRLQVVQA KQVERHIQHQ LGGFLEKTLS KLPNLESLRP RSQLMLTRKA EAALRKAASE
TTTSEGLSNF LKSNSISEEL ERFTASGIAN LRCSEQAFDS DVTDSSSGGE SDIEEEELTR
ADPEQRHVPL RRRSEWKWAA DRAAIVSRWN WLQAHVSDLE YRIRQQTDIY KQIRANKGLI
VLGEVPPPEH TTDLFLPLSS EVKTDHGTDK LIESVSQPLE NHGARIIGHI SESLSTKSCG
ALRPVNGVIN TLQPVLADHI PGDSSDAEEQ LHKKQRLNLV SSSSDGTCVA ARTRPVLSCK
KRRLVRPNSI VPLSKKVHRN STIRPGCDVN PSCALCGSGS INTMPPEIHY EAPLLERLSQ
LDSCVHPVLA FPDDVPTSLH FQSMLKSQWQ NKPFDKIKPP KKLSLKHRAP MPGSLPDSAR
KDRHKLVSSF LTTAKLSHHQ TRPDRTHRQH LDDVGAVPMV ERVTAPKAER LLNPPPPVHD
PNHSKMRLRD HSSERSEVLK HHTDMSSSSY LAATHHPPHS PLVRQLSTSS DSPAPASSSS
QVTASTSQQP VRRRRGESSF DINNIVIPMS VAATTRVEKL QYKEILTPSW REVDLQSLKG
SPDEENEEIE DLSDAAFAAL HAKCEEMERA RWLWTTSVPP QRRGSRSYRS SDGRTTPQLG
SANPSTPQPA SPDVSSSHSL SEYSHGQSPR SPISPELHSA PLTPVARDTP RHLASEDTRC
STPELGLDEQ SVQPWERRTF PLAHSPQAEC EDQLDAQERA ARCTRRTSGS KTGRETEAAP
TSPPIVPLKS RHLVAAATAQ RPTHR
