KDM6A_HUMAN
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 03-AUG-2022, entry version 204.
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 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 [15]
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 [16]
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). {ECO:0000250|UniProtKB:O70546,
CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:17713478}.
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}.
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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; 145.
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; 76.
DR MINT; O15550; -.
DR STRING; 9606.ENSP00000367203; -.
DR BindingDB; O15550; -.
DR ChEMBL; CHEMBL2069164; -.
DR GuidetoPHARMACOLOGY; 2684; -.
DR GlyGen; O15550; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O15550; -.
DR PhosphoSitePlus; O15550; -.
DR BioMuta; KDM6A; -.
DR EPD; O15550; -.
DR jPOST; O15550; -.
DR MassIVE; O15550; -.
DR MaxQB; O15550; -.
DR PaxDb; O15550; -.
DR PeptideAtlas; O15550; -.
DR PRIDE; O15550; -.
DR ProteomicsDB; 48752; -.
DR Antibodypedia; 639; 209 antibodies from 26 providers.
DR DNASU; 7403; -.
DR Ensembl; ENST00000377967.9; ENSP00000367203.4; ENSG00000147050.17.
DR GeneID; 7403; -.
DR KEGG; hsa:7403; -.
DR UCSC; uc004dge.5; human.
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; 268901at2759; -.
DR PhylomeDB; O15550; -.
DR TreeFam; TF317405; -.
DR BioCyc; MetaCyc:ENSG00000147050-MON; -.
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 SignaLink; O15550; -.
DR SIGNOR; O15550; -.
DR BioGRID-ORCS; 7403; 36 hits in 722 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 198 other tissues.
DR ExpressionAtlas; O15550; baseline and differential.
DR Genevisible; O15550; HS.
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 H3-tri/di-methyl-lysine-27 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:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0071557; P:histone H3-K27 demethylation; IBA:GO_Central.
DR GO; GO:0051568; P:histone H3-K4 methylation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR Gene3D; 1.25.40.10; -; 2.
DR IDEAL; IID00431; -.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00028; TPR; 6.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS50005; TPR; 7.
DR PROSITE; PS50293; TPR_REGION; 1.
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
