ID KDM6A_HUMAN Reviewed; 1401 AA. AC O15550; Q52LL9; Q5JVQ7; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 23-SEP-2008, sequence version 2. DT 24-JAN-2024, entry version 212. DE RecName: Full=Lysine-specific demethylase 6A; DE EC=1.14.11.68 {ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914}; DE AltName: Full=Histone demethylase UTX; DE AltName: Full=Ubiquitously-transcribed TPR protein on the X chromosome; DE AltName: Full=Ubiquitously-transcribed X chromosome tetratricopeptide repeat protein; DE AltName: Full=[histone H3]-trimethyl-L-lysine(27) demethylase 6A {ECO:0000305}; GN Name=KDM6A; Synonyms=UTX; 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]. RX PubMed=9381176; DOI=10.1126/science.278.5338.675; RA Lahn B.T., Page D.C.; RT "Functional coherence of the human Y chromosome."; RL Science 278:675-680(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-726. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MLL2/3 RP COMPLEX. RX PubMed=17500065; DOI=10.1074/jbc.m701574200; RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T., RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.; RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 RT methyltransferase complex."; RL J. Biol. Chem. 282:20395-20406(2007). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1146. RX PubMed=17851529; DOI=10.1038/nature06192; RA Lan F., Bayliss P.E., Rinn J.L., Whetstine J.R., Wang J.K., Chen S., RA Iwase S., Alpatov R., Issaeva I., Canaani E., Roberts T.M., Chang H.Y., RA Shi Y.; RT "A histone H3 lysine 27 demethylase regulates animal posterior RT development."; RL Nature 449:689-694(2007). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=17713478; DOI=10.1038/nature06145; RA Agger K., Cloos P.A., Christensen J., Pasini D., Rose S., Rappsilber J., RA Issaeva I., Canaani E., Salcini A.E., Helin K.; RT "UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene RT regulation and development."; RL Nature 449:731-734(2007). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1146. RX PubMed=18003914; DOI=10.1073/pnas.0707292104; RA Hong S., Cho Y.W., Yu L.-R., Yu H., Veenstra T.D., Ge K.; RT "Identification of JmjC domain-containing UTX and JMJD3 as histone H3 RT lysine 27 demethylases."; RL Proc. Natl. Acad. Sci. U.S.A. 104:18439-18444(2007). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF HIS-1146, AND RP IDENTIFICATION IN THE MLL2/3 COMPLEX. RX PubMed=17761849; DOI=10.1126/science.1149042; RA Lee M.G., Villa R., Trojer P., Norman J., Yan K.P., Reinberg D., RA Di Croce L., Shiekhattar R.; RT "Demethylation of H3K27 regulates polycomb recruitment and H2A RT ubiquitination."; RL Science 318:447-450(2007). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-769 AND SER-829, AND RP IDENTIFICATION BY 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 [12] RP INVOLVEMENT IN KABUK2. RX PubMed=22197486; DOI=10.1016/j.ajhg.2011.11.021; RA Lederer D., Grisart B., Digilio M.C., Benoit V., Crespin M., Ghariani S.C., RA Maystadt I., Dallapiccola B., Verellen-Dumoulin C.; RT "Deletion of KDM6A, a histone demethylase interacting with MLL2, in three RT patients with Kabuki syndrome."; RL Am. J. Hum. Genet. 90:119-124(2012). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP INTERACTION WITH PROSER1, AND IDENTIFICATION IN THE MLL3/4 COMPLEX. RX PubMed=34667079; DOI=10.26508/lsa.202101228; RA Wang X., Rosikiewicz W., Sedkov Y., Martinez T., Hansen B.S., Schreiner P., RA Christensen J., Xu B., Pruett-Miller S.M., Helin K., Herz H.M.; RT "PROSER1 mediates TET2 O-GlcNAcylation to regulate DNA demethylation on RT UTX-dependent enhancers and CpG islands."; RL Life. Sci Alliance 5:0-0(2022). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 880-1401 IN COMPLEX WITH HISTONE RP H3 PEPTIDE, IRON-BINDING SITES, AND ZINC-BINDING SITES. RX PubMed=22002947; DOI=10.1101/gad.172296.111; RA Sengoku T., Yokoyama S.; RT "Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A."; RL Genes Dev. 25:2266-2277(2011). RN [16] RP VARIANT [LARGE SCALE ANALYSIS] ARG-1106. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [17] RP VARIANTS VAL-270; ASP-834 AND LYS-922. RX PubMed=21828135; DOI=10.1182/blood-2010-10-311019; RA Jankowska A.M., Makishima H., Tiu R.V., Szpurka H., Huang Y., Traina F., RA Visconte V., Sugimoto Y., Prince C., O'Keefe C., Hsi E.D., List A., RA Sekeres M.A., Rao A., McDevitt M.A., Maciejewski J.P.; RT "Mutational spectrum analysis of chronic myelomonocytic leukemia includes RT genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A."; RL Blood 118:3932-3941(2011). CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-27' CC of histone H3, thereby playing a central role in histone code CC (PubMed:17851529, PubMed:17713478, PubMed:17761849). Demethylates CC trimethylated and dimethylated but not monomethylated H3 'Lys-27' CC (PubMed:17851529, PubMed:17713478, PubMed:17761849). Plays a central CC role in regulation of posterior development, by regulating HOX gene CC expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 CC is concomitant with methylation of 'Lys-4' of histone H3, and regulates CC the recruitment of the PRC1 complex and monoubiquitination of histone CC H2A (PubMed:17761849). Plays a demethylase-independent role in CC chromatin remodeling to regulate T-box family member-dependent gene CC expression (By similarity). {ECO:0000250|UniProtKB:O70546, CC ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, CC ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(27)- CC [histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + N(6)-methyl-L- CC lysyl(27)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:60224, CC Rhea:RHEA-COMP:15535, Rhea:RHEA-COMP:15544, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61929, ChEBI:CHEBI:61961; CC EC=1.14.11.68; Evidence={ECO:0000269|PubMed:17713478, CC ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, CC ECO:0000269|PubMed:18003914}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC Evidence={ECO:0000269|PubMed:17761849}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:17761849}; CC -!- SUBUNIT: Interacts with TLE1 (By similarity). Component of the MLL2/3 CC complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or CC KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A (or KDM6B), CC PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (PubMed:17500065, CC PubMed:17713478). Interacts with SUPT6H. Interacts with SMARCA4 (By CC similarity). Interacts with PROSER1 (PubMed:34667079). CC {ECO:0000250|UniProtKB:O70546, ECO:0000269|PubMed:17500065, CC ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:34667079}. CC -!- INTERACTION: CC O15550; O15499: GSC2; NbExp=3; IntAct=EBI-4292203, EBI-19954058; CC O15550; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-4292203, EBI-16439278; CC O15550; P61964: WDR5; NbExp=6; IntAct=EBI-4292203, EBI-540834; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- DISEASE: Kabuki syndrome 2 (KABUK2) [MIM:300867]: A congenital CC intellectual disability syndrome with additional features, including CC postnatal dwarfism, a peculiar facies characterized by long palpebral CC fissures with eversion of the lateral third of the lower eyelids, a CC broad and depressed nasal tip, large prominent earlobes, a cleft or CC high-arched palate, scoliosis, short fifth finger, persistence of CC fingerpads, radiographic abnormalities of the vertebrae, hands, and hip CC joints, and recurrent otitis media in infancy. CC {ECO:0000269|PubMed:22197486}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Escapes X chromosome inactivation. CC -!- SIMILARITY: Belongs to the UTX family. {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; AF000992; AAC51839.1; -; mRNA. DR EMBL; AF000993; AAC51840.1; -; mRNA. DR EMBL; AC136488; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133545; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL138744; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471141; EAW59368.1; -; Genomic_DNA. DR EMBL; BC093868; AAH93868.1; -; mRNA. DR EMBL; BC113381; AAI13382.1; -; mRNA. DR CCDS; CCDS14265.1; -. DR PIR; T02255; T02255. DR RefSeq; NP_066963.2; NM_021140.3. DR PDB; 3AVR; X-ray; 1.80 A; A=880-1401. DR PDB; 3AVS; X-ray; 1.85 A; A=880-1401. DR PDB; 6FUK; X-ray; 2.00 A; A=877-1401. DR PDB; 6FUL; X-ray; 1.65 A; A=877-1401. DR PDBsum; 3AVR; -. DR PDBsum; 3AVS; -. DR PDBsum; 6FUK; -. DR PDBsum; 6FUL; -. DR AlphaFoldDB; O15550; -. DR SMR; O15550; -. DR BioGRID; 113246; 150. DR ComplexPortal; CPX-7091; Histone-lysine N-methyltransferase complex, KMT2C variant. DR ComplexPortal; CPX-7104; Histone-lysine N-methyltransferase complex, KMT2D variant. DR CORUM; O15550; -. DR DIP; DIP-46192N; -. DR IntAct; O15550; 80. DR MINT; O15550; -. DR STRING; 9606.ENSP00000367203; -. DR BindingDB; O15550; -. DR ChEMBL; CHEMBL2069164; -. DR GuidetoPHARMACOLOGY; 2684; -. DR GlyCosmos; O15550; 2 sites, 1 glycan. DR GlyGen; O15550; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; O15550; -. DR PhosphoSitePlus; O15550; -. DR BioMuta; KDM6A; -. DR EPD; O15550; -. DR jPOST; O15550; -. DR MassIVE; O15550; -. DR MaxQB; O15550; -. DR PaxDb; 9606-ENSP00000367203; -. DR PeptideAtlas; O15550; -. DR ProteomicsDB; 48752; -. DR Pumba; O15550; -. DR Antibodypedia; 639; 237 antibodies from 27 providers. DR DNASU; 7403; -. DR Ensembl; ENST00000377967.9; ENSP00000367203.4; ENSG00000147050.18. DR GeneID; 7403; -. DR KEGG; hsa:7403; -. DR UCSC; uc004dge.5; human. DR AGR; HGNC:12637; -. DR CTD; 7403; -. DR DisGeNET; 7403; -. DR GeneCards; KDM6A; -. DR GeneReviews; KDM6A; -. DR HGNC; HGNC:12637; KDM6A. DR HPA; ENSG00000147050; Low tissue specificity. DR MalaCards; KDM6A; -. DR MIM; 300128; gene. DR MIM; 300867; phenotype. DR neXtProt; NX_O15550; -. DR OpenTargets; ENSG00000147050; -. DR Orphanet; 2322; Kabuki syndrome. DR PharmGKB; PA37262; -. DR VEuPathDB; HostDB:ENSG00000147050; -. DR eggNOG; KOG1124; Eukaryota. DR eggNOG; KOG1246; Eukaryota. DR GeneTree; ENSGT00940000155202; -. DR InParanoid; O15550; -. DR OrthoDB; 20251at2759; -. DR PhylomeDB; O15550; -. DR TreeFam; TF317405; -. DR BioCyc; MetaCyc:ENSG00000147050-MONOMER; -. DR BRENDA; 1.14.11.68; 2681. DR PathwayCommons; O15550; -. DR Reactome; R-HSA-3214842; HDMs demethylate histones. DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis. DR Reactome; R-HSA-9772755; Formation of WDR5-containing histone-modifying complexes. DR Reactome; R-HSA-9821002; Chromatin modifications during the maternal to zygotic transition (MZT). DR SignaLink; O15550; -. DR SIGNOR; O15550; -. DR BioGRID-ORCS; 7403; 51 hits in 822 CRISPR screens. DR ChiTaRS; KDM6A; human. DR GeneWiki; UTX_(gene); -. DR GenomeRNAi; 7403; -. DR Pharos; O15550; Tchem. DR PRO; PR:O15550; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O15550; Protein. DR Bgee; ENSG00000147050; Expressed in secondary oocyte and 200 other cell types or tissues. DR ExpressionAtlas; O15550; baseline and differential. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI. DR GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0031490; F:chromatin DNA binding; IBA:GO_Central. DR GO; GO:0032452; F:histone demethylase activity; TAS:Reactome. DR GO; GO:0071558; F:histone H3K27me2/H3K27me3 demethylase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR Gene3D; 1.20.58.1370; -; 2. DR Gene3D; 2.10.110.20; -; 1. DR Gene3D; 2.60.120.650; Cupin; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 2. DR IDEAL; IID00431; -. DR InterPro; IPR003347; JmjC_dom. DR InterPro; IPR046941; KDM6_GATAL_sf. DR InterPro; IPR048562; KDM6A_B-like_C-hel. DR InterPro; IPR048560; KDM6A_B-like_GATAL. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR14017; LYSINE-SPECIFIC DEMETHYLASE; 1. DR PANTHER; PTHR14017:SF9; LYSINE-SPECIFIC DEMETHYLASE 6A; 1. DR Pfam; PF02373; JmjC; 1. DR Pfam; PF21322; KDM6_C-hel; 1. DR Pfam; PF21326; KDM6_GATAL; 1. DR Pfam; PF13432; TPR_16; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00558; JmjC; 1. DR SMART; SM00028; TPR; 6. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR SUPFAM; SSF48452; TPR-like; 2. DR PROSITE; PS51184; JMJC; 1. DR PROSITE; PS50005; TPR; 7. DR PROSITE; PS50293; TPR_REGION; 1. DR Genevisible; O15550; HS. PE 1: Evidence at protein level; KW 3D-structure; Chromatin regulator; Dioxygenase; Intellectual disability; KW Iron; Metal-binding; Methylation; Nucleus; Oxidoreductase; Phosphoprotein; KW Reference proteome; Repeat; TPR repeat; Zinc. FT CHAIN 1..1401 FT /note="Lysine-specific demethylase 6A" FT /id="PRO_0000106409" FT REPEAT 93..126 FT /note="TPR 1" FT REPEAT 130..163 FT /note="TPR 2" FT REPEAT 170..199 FT /note="TPR 3" FT REPEAT 205..238 FT /note="TPR 4" FT REPEAT 250..283 FT /note="TPR 5" FT REPEAT 284..317 FT /note="TPR 6" FT REPEAT 318..351 FT /note="TPR 7" FT REPEAT 352..385 FT /note="TPR 8" FT DOMAIN 1095..1258 FT /note="JmjC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538" FT REGION 1..1095 FT /note="Interaction with SUPT6H" FT /evidence="ECO:0000250" FT REGION 437..457 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 521..541 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 624..746 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 758..778 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 810..864 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 914..940 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1043..1079 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 810..862 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 917..937 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1046..1076 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1146 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:22002947" FT BINDING 1148 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:22002947" FT BINDING 1226 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:22002947" FT BINDING 1331 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22002947" FT BINDING 1334 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22002947" FT BINDING 1358 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22002947" FT BINDING 1361 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22002947" FT MOD_RES 519 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:O70546" FT MOD_RES 549 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:O70546" FT MOD_RES 769 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 827 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O70546" FT MOD_RES 829 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT VARIANT 30 FT /note="A -> T (in dbSNP:rs6529)" FT /id="VAR_014492" FT VARIANT 270 FT /note="I -> V (in a patient with chronic myelomonocytic FT leukemia)" FT /evidence="ECO:0000269|PubMed:21828135" FT /id="VAR_067225" FT VARIANT 497 FT /note="Q -> H (in dbSNP:rs6530)" FT /id="VAR_014493" FT VARIANT 581 FT /note="T -> A (in dbSNP:rs34922269)" FT /id="VAR_046527" FT VARIANT 726 FT /note="T -> K (in dbSNP:rs2230018)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_020313" FT VARIANT 834 FT /note="E -> D (in a patient with chronic myelomonocytic FT leukemia)" FT /evidence="ECO:0000269|PubMed:21828135" FT /id="VAR_067226" FT VARIANT 922 FT /note="R -> K (in a patient with chronic myelomonocytic FT leukemia)" FT /evidence="ECO:0000269|PubMed:21828135" FT /id="VAR_067227" FT VARIANT 1106 FT /note="L -> R (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035871" FT MUTAGEN 1146 FT /note="H->A: Abolishes histone demethylase activity." FT /evidence="ECO:0000269|PubMed:17761849, FT ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914" FT CONFLICT 173 FT /note="L -> V (in Ref. 1; AAC51839/AAC51840)" FT /evidence="ECO:0000305" FT CONFLICT 585 FT /note="L -> R (in Ref. 1; AAC51839/AAC51840)" FT /evidence="ECO:0000305" FT CONFLICT 601 FT /note="S -> N (in Ref. 1; AAC51839/AAC51840)" FT /evidence="ECO:0000305" FT CONFLICT 629 FT /note="E -> K (in Ref. 1; AAC51839/AAC51840)" FT /evidence="ECO:0000305" FT HELIX 893..900 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 933..935 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 942..944 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 948..951 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 955..961 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 966..971 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 973..977 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 981..984 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 986..993 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 997..1004 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1016..1019 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1025..1031 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1032..1047 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1081..1089 FT /evidence="ECO:0007829|PDB:6FUL" FT TURN 1093..1095 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1097..1103 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1108..1110 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1118..1121 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1122..1124 FT /evidence="ECO:0007829|PDB:6FUL" FT TURN 1127..1129 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1133..1137 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1142..1146 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1149..1151 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1153..1162 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1164..1169 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1171..1173 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1174..1183 FT /evidence="ECO:0007829|PDB:6FUL" FT TURN 1188..1190 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1197..1202 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1208..1212 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1217..1220 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1225..1241 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1243..1245 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1246..1262 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1270..1280 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1286..1312 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1317..1319 FT /evidence="ECO:0007829|PDB:6FUL" FT TURN 1332..1334 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1340..1345 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1346..1350 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1351..1357 FT /evidence="ECO:0007829|PDB:3AVR" FT HELIX 1359..1365 FT /evidence="ECO:0007829|PDB:6FUL" FT STRAND 1372..1376 FT /evidence="ECO:0007829|PDB:6FUL" FT HELIX 1380..1389 FT /evidence="ECO:0007829|PDB:6FUL" SQ SEQUENCE 1401 AA; 154177 MW; 9DD7EA6C61E79229 CRC64; MKSCGVSLAT AAAAAAAFGD EEKKMAAGKA SGESEEASPS LTAEEREALG GLDSRLFGFV RFHEDGARTK ALLGKAVRCY ESLILKAEGK VESDFFCQLG HFNLLLEDYP KALSAYQRYY SLQSDYWKNA AFLYGLGLVY FHYNAFQWAI KAFQEVLYVD PSFCRAKEIH LRLGLMFKVN TDYESSLKHF QLALVDCNPC TLSNAEIQFH IAHLYETQRK YHSAKEAYEQ LLQTENLSAQ VKATVLQQLG WMHHTVDLLG DKATKESYAI QYLQKSLEAD PNSGQSWYFL GRCYSSIGKV QDAFISYRQS IDKSEASADT WCSIGVLYQQ QNQPMDALQA YICAVQLDHG HAAAWMDLGT LYESCNQPQD AIKCYLNATR SKSCSNTSAL AARIKYLQAQ LCNLPQGSLQ NKTKLLPSIE EAWSLPIPAE LTSRQGAMNT AQQNTSDNWS GGHAVSHPPV QQQAHSWCLT PQKLQHLEQL RANRNNLNPA QKLMLEQLES QFVLMQQHQM RPTGVAQVRS TGIPNGPTAD SSLPTNSVSG QQPQLALTRV PSVSQPGVRP ACPGQPLANG PFSAGHVPCS TSRTLGSTDT ILIGNNHITG SGSNGNVPYL QRNALTLPHN RTNLTSSAEE PWKNQLSNST QGLHKGQSSH SAGPNGERPL SSTGPSQHLQ AAGSGIQNQN GHPTLPSNSV TQGAALNHLS SHTATSGGQQ GITLTKESKP SGNILTVPET SRHTGETPNS TASVEGLPNH VHQMTADAVC SPSHGDSKSP GLLSSDNPQL SALLMGKANN NVGTGTCDKV NNIHPAVHTK TDNSVASSPS SAISTATPSP KSTEQTTTNS VTSLNSPHSG LHTINGEGME ESQSPMKTDL LLVNHKPSPQ IIPSMSVSIY PSSAEVLKAC RNLGKNGLSN SSILLDKCPP PRPPSSPYPP LPKDKLNPPT PSIYLENKRD AFFPPLHQFC TNPNNPVTVI RGLAGALKLD LGLFSTKTLV EANNEHMVEV RTQLLQPADE NWDPTGTKKI WHCESNRSHT TIAKYAQYQA SSFQESLREE NEKRSHHKDH SDSESTSSDN SGRRRKGPFK TIKFGTNIDL SDDKKWKLQL HELTKLPAFV RVVSAGNLLS HVGHTILGMN TVQLYMKVPG SRTPGHQENN NFCSVNINIG PGDCEWFVVP EGYWGVLNDF CEKNNLNFLM GSWWPNLEDL YEANVPVYRF IQRPGDLVWI NAGTVHWVQA IGWCNNIAWN VGPLTACQYK LAVERYEWNK LQSVKSIVPM VHLSWNMARN IKVSDPKLFE MIKYCLLRTL KQCQTLREAL IAAGKEIIWH GRTKEEPAHY CSICEVEVFD LLFVTNESNS RKTYIVHCQD CARKTSGNLE NFVVLEQYKM EDLMQVYDQF TLAPPLPSAS S //