ID   F5H6S1_HUMAN            Unreviewed;      1356 AA.
AC   F5H6S1;
DT   28-JUN-2011, integrated into UniProtKB/TrEMBL.
DT   02-DEC-2020, sequence version 3.
DT   27-MAR-2024, entry version 95.
DE   RecName: Full=[histone H3]-trimethyl-L-lysine(27) demethylase {ECO:0000256|ARBA:ARBA00034525};
DE            EC=1.14.11.68 {ECO:0000256|ARBA:ARBA00034525};
GN   Name=KDM6A {ECO:0000313|Ensembl:ENSP00000437405.3};
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 {ECO:0000313|Ensembl:ENSP00000437405.3, ECO:0000313|Proteomes:UP000005640};
RN   [1] {ECO:0000313|Ensembl:ENSP00000437405.3, ECO:0000313|Proteomes:UP000005640}
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   [2] {ECO:0007829|PubMed:19413330}
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   [3] {ECO:0007829|PubMed:19690332}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [4] {ECO:0007829|PubMed:23186163}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=23186163;
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   [5] {ECO:0000313|Ensembl:ENSP00000437405.3}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00034421};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000256|ARBA:ARBA00001954};
CC   -!- COFACTOR:
CC       Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC         Evidence={ECO:0000256|ARBA:ARBA00001961};
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|ARBA:ARBA00004123}.
CC   -!- SIMILARITY: Belongs to the UTX family. {ECO:0000256|ARBA:ARBA00034483}.
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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; KF510678; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001278346.1; NM_001291417.1.
DR   SMR; F5H6S1; -.
DR   MassIVE; F5H6S1; -.
DR   PeptideAtlas; F5H6S1; -.
DR   ProteomicsDB; 27272; -.
DR   Antibodypedia; 639; 237 antibodies from 27 providers.
DR   Ensembl; ENST00000536777.6; ENSP00000437405.3; ENSG00000147050.18.
DR   GeneID; 7403; -.
DR   UCSC; uc064yrv.1; human.
DR   CTD; 7403; -.
DR   HGNC; HGNC:12637; KDM6A.
DR   VEuPathDB; HostDB:ENSG00000147050; -.
DR   GeneTree; ENSGT00940000155202; -.
DR   HOGENOM; CLU_003187_0_0_1; -.
DR   OrthoDB; 20251at2759; -.
DR   ChiTaRS; KDM6A; human.
DR   Proteomes; UP000005640; Chromosome X.
DR   Bgee; ENSG00000147050; Expressed in secondary oocyte and 200 other cell types or tissues.
DR   ExpressionAtlas; F5H6S1; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0032452; F:histone demethylase activity; IEA:UniProt.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
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   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; 2.
PE   1: Evidence at protein level;
KW   Iron {ECO:0000256|ARBA:ARBA00023004};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Nucleus {ECO:0000256|ARBA:ARBA00023242};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW   Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Proteomics identification {ECO:0007829|EPD:F5H6S1,
KW   ECO:0007829|MaxQB:F5H6S1};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}.
FT   REPEAT          130..163
FT                   /note="TPR"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU00339"
FT   REPEAT          318..351
FT                   /note="TPR"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU00339"
FT   DOMAIN          1050..1213
FT                   /note="JmjC"
FT                   /evidence="ECO:0000259|PROSITE:PS51184"
FT   REGION          579..701
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          713..733
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          765..819
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          869..895
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          998..1034
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        765..817
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        872..892
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1001..1031
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   1356 AA;  149317 MW;  C2B91A66F2166107 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 AARIKYLQNT SDNWSGGHAV SHPPVQQQAH
     SWCLTPQKLQ HLEQLRANRN NLNPAQKLML EQLESQFVLM QQHQMRPTGV AQVRSTGIPN
     GPTADSSLPT NSVSGQQPQL ALTRVPSVSQ PGVRPACPGQ PLANGPFSAG HVPCSTSRTL
     GSTDTILIGN NHITGSGSNG NVPYLQRNAL TLPHNRTNLT SSAEEPWKNQ LSNSTQGLHK
     GQSSHSAGPN GERPLSSTGP SQHLQAAGSG IQNQNGHPTL PSNSVTQGAA LNHLSSHTAT
     SGGQQGITLT KESKPSGNIL TVPETSRHTG ETPNSTASVE GLPNHVHQMT ADAVCSPSHG
     DSKSPGLLSS DNPQLSALLM GKANNNVGTG TCDKVNNIHP AVHTKTDNSV ASSPSSAIST
     ATPSPKSTEQ TTTNSVTSLN SPHSGLHTIN GEGMEESQSP MKTDLLLVNH KPSPQIIPSM
     SVSIYPSSAE VLKACRNLGK NGLSNSSILL DKCPPPRPPS SPYPPLPKDK LNPPTPSIYL
     ENKRDAFFPP LHQFCTNPNN PVTVIRGLAG ALKLDLGLFS TKTLVEANNE HMVEVRTQLL
     QPADENWDPT GTKKIWHCES NRSHTTIAKY AQYQASSFQE SLREENEKRS HHKDHSDSES
     TSSDNSGRRR KGPFKTIKFG TNIDLSDDKK WKLQLHELTK LPAFVRVVSA GNLLSHVGHT
     ILGMNTVQLY MKVPGSRTPG HQENNNFCSV NINIGPGDCE WFVVPEGYWG VLNDFCEKNN
     LNFLMGSWWP NLEDLYEANV PVYRFIQRPG DLVWINAGTV HWVQAIGWCN NIAWNVGPLT
     ACQYKLAVER YEWNKLQSVK SIVPMVHLSW NMARNIKVSD PKLFEMIKYC LLRTLKQCQT
     LREALIAAGK EIIWHGRTKE EPAHYCSICE VEVFDLLFVT NESNSRKTYI VHCQDCARKT
     SGNLENFVVL EQYKMEDLMQ VYDQFTLAPP LPSASS
//