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 28-JUN-2023, sequence version 3. DT 27-MAR-2024, entry version 163. 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. [Q7Z3B3-1] DR RefSeq; NP_056258.1; NM_015443.3. [Q7Z3B3-1] 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; 96. DR ComplexPortal; CPX-809; NSL histone acetyltransferase complex. DR CORUM; Q7Z3B3; -. DR ELM; Q7Z3B3; -. DR IntAct; Q7Z3B3; 54. DR MINT; Q7Z3B3; -. DR STRING; 9606.ENSP00000387393; -. DR MoonProt; Q7Z3B3; -. DR GlyGen; Q7Z3B3; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000262419; -. DR PeptideAtlas; Q7Z3B3; -. DR ProteomicsDB; 47521; -. DR ProteomicsDB; 69022; -. [Q7Z3B3-1] DR ProteomicsDB; 69023; -. [Q7Z3B3-2] DR Pumba; Q7Z3B3; -. DR Antibodypedia; 2016; 92 antibodies from 15 providers. DR DNASU; 284058; -. DR Ensembl; ENST00000262419.10; ENSP00000262419.6; ENSG00000120071.15. [Q7Z3B3-1] DR Ensembl; ENST00000432791.7; ENSP00000387393.3; ENSG00000120071.15. [Q7Z3B3-1] DR Ensembl; ENST00000572904.6; ENSP00000461484.1; ENSG00000120071.15. [Q7Z3B3-1] DR GeneID; 284058; -. DR KEGG; hsa:284058; -. DR MANE-Select; ENST00000432791.7; ENSP00000387393.3; NM_015443.4; NP_056258.1. DR UCSC; uc002ikc.4; human. [Q7Z3B3-1] DR UCSC; uc060gjw.1; human. DR AGR; HGNC:24565; -. 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 OpenTargets; ENSG00000120071; -. 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 GeneTree; ENSGT00530000063688; -. DR InParanoid; Q7Z3B3; -. DR OMA; ERHAKCE; -. DR OrthoDB; 5359304at2759; -. DR PhylomeDB; Q7Z3B3; -. DR TreeFam; TF336511; -. DR PathwayCommons; Q7Z3B3; -. DR Reactome; R-HSA-3214847; HATs acetylate histones. DR Reactome; R-HSA-9772755; Formation of WDR5-containing histone-modifying complexes. DR SignaLink; Q7Z3B3; -. DR SIGNOR; Q7Z3B3; -. DR BioGRID-ORCS; 284058; 487 hits in 1168 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 176 other cell types or tissues. DR ExpressionAtlas; Q7Z3B3; baseline and differential. 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:0045893; P:positive regulation of DNA-templated transcription; NAS:ComplexPortal. DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:ComplexPortal. DR Gene3D; 6.10.250.3170; -; 1. DR InterPro; IPR026180; NSL1. DR InterPro; IPR029332; PEHE_dom. DR PANTHER; PTHR22443:SF14; KAT8 REGULATORY NSL COMPLEX SUBUNIT 1; 1. DR PANTHER; PTHR22443; NON-SPECIFIC LETHAL 1, ISOFORM M; 1. DR Pfam; PF15275; PEHE; 1. DR SMART; SM01300; PEHE; 1. DR Genevisible; Q7Z3B3; HS. 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 1058..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 COMPBIAS 1058..1072 FT /note="Basic and acidic 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 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; 120966 MW; 240A04F652B717DA 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 NHGAPIIGHI 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 //