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Protein

Lysine-specific demethylase 6A

Gene

KDM6A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A.2 Publications

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1146Iron1 Publication1
Metal bindingi1148Iron1 Publication1
Metal bindingi1226Iron1 Publication1
Metal bindingi1331Zinc1 Publication1
Metal bindingi1334Zinc1 Publication1
Metal bindingi1358Zinc1 Publication1
Metal bindingi1361Zinc1 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000147050-MONOMER.
ReactomeiR-HSA-3214842. HDMs demethylate histones.
R-HSA-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase 6A (EC:1.14.11.-)
Alternative name(s):
Histone demethylase UTX
Ubiquitously-transcribed TPR protein on the X chromosome
Ubiquitously-transcribed X chromosome tetratricopeptide repeat protein
Gene namesi
Name:KDM6A
Synonyms:UTX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:12637. KDM6A.

Subcellular locationi

GO - Cellular componenti

  • histone methyltransferase complex Source: MGI
  • MLL3/4 complex Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Kabuki syndrome 2 (KABUK2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.
See also OMIM:300867

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1146H → A: Abolishes histone demethylase activity. 3 Publications1

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi7403.
MalaCardsiKDM6A.
MIMi300867. phenotype.
OpenTargetsiENSG00000147050.
Orphaneti2322. Kabuki syndrome.
PharmGKBiPA37262.

Chemistry databases

ChEMBLiCHEMBL2069164.
GuidetoPHARMACOLOGYi2684.

Polymorphism and mutation databases

BioMutaiKDM6A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001064091 – 1401Lysine-specific demethylase 6AAdd BLAST1401

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei519Omega-N-methylarginineBy similarity1
Modified residuei549Omega-N-methylarginineBy similarity1
Modified residuei769PhosphoserineCombined sources1
Modified residuei827PhosphothreonineBy similarity1
Modified residuei829PhosphoserineCombined sources1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiO15550.
MaxQBiO15550.
PaxDbiO15550.
PeptideAtlasiO15550.
PRIDEiO15550.

PTM databases

iPTMnetiO15550.
PhosphoSitePlusiO15550.

Expressioni

Gene expression databases

BgeeiENSG00000147050.
CleanExiHS_UTX.
ExpressionAtlasiO15550. baseline and differential.
GenevisibleiO15550. HS.

Organism-specific databases

HPAiHPA000568.
HPA001165.
HPA002111.

Interactioni

Subunit structurei

Interacts with TLE1 (By similarity). Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A (or KDM6B), PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with SUPT6H (By similarity).By similarity

Protein-protein interaction databases

BioGridi113246. 27 interactors.
DIPiDIP-46192N.
IntActiO15550. 13 interactors.
MINTiMINT-1188304.
STRINGi9606.ENSP00000367203.

Chemistry databases

BindingDBiO15550.

Structurei

Secondary structure

11401
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi893 – 900Combined sources8
Helixi933 – 935Combined sources3
Beta strandi942 – 944Combined sources3
Helixi948 – 951Combined sources4
Helixi954 – 961Combined sources8
Beta strandi966 – 971Combined sources6
Helixi973 – 977Combined sources5
Helixi981 – 984Combined sources4
Helixi986 – 992Combined sources7
Beta strandi997 – 1004Combined sources8
Beta strandi1016 – 1019Combined sources4
Beta strandi1025 – 1031Combined sources7
Helixi1032 – 1045Combined sources14
Beta strandi1081 – 1089Combined sources9
Turni1093 – 1096Combined sources4
Helixi1097 – 1102Combined sources6
Helixi1103 – 1105Combined sources3
Helixi1108 – 1110Combined sources3
Helixi1118 – 1121Combined sources4
Beta strandi1122 – 1124Combined sources3
Turni1127 – 1129Combined sources3
Beta strandi1133 – 1137Combined sources5
Beta strandi1142 – 1146Combined sources5
Helixi1149 – 1151Combined sources3
Beta strandi1153 – 1162Combined sources10
Beta strandi1164 – 1169Combined sources6
Helixi1171 – 1173Combined sources3
Helixi1174 – 1183Combined sources10
Turni1188 – 1190Combined sources3
Helixi1197 – 1202Combined sources6
Beta strandi1208 – 1212Combined sources5
Beta strandi1217 – 1220Combined sources4
Beta strandi1225 – 1241Combined sources17
Beta strandi1243 – 1245Combined sources3
Helixi1246 – 1262Combined sources17
Helixi1270 – 1280Combined sources11
Helixi1286 – 1312Combined sources27
Beta strandi1317 – 1319Combined sources3
Turni1332 – 1334Combined sources3
Beta strandi1340 – 1346Combined sources7
Beta strandi1351 – 1357Combined sources7
Helixi1359 – 1365Combined sources7
Beta strandi1373 – 1376Combined sources4
Helixi1380 – 1388Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AVRX-ray1.80A880-1401[»]
3AVSX-ray1.85A880-1401[»]
ProteinModelPortaliO15550.
SMRiO15550.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati93 – 126TPR 1Add BLAST34
Repeati130 – 163TPR 2Add BLAST34
Repeati170 – 199TPR 3Add BLAST30
Repeati205 – 238TPR 4Add BLAST34
Repeati250 – 283TPR 5Add BLAST34
Repeati284 – 317TPR 6Add BLAST34
Repeati318 – 351TPR 7Add BLAST34
Repeati352 – 385TPR 8Add BLAST34
Domaini1095 – 1258JmjCPROSITE-ProRule annotationAdd BLAST164

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 1095Interaction with SUPT6HBy similarityAdd BLAST1095

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi9 – 17Poly-Ala9

Sequence similaritiesi

Belongs to the UTX family.Curated
Contains 1 JmjC domain.PROSITE-ProRule annotation
Contains 8 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
KOG1246. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00410000025758.
InParanoidiO15550.
KOiK11447.
PhylomeDBiO15550.
TreeFamiTF317405.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR003347. JmjC_dom.
IPR029517. KDM6A.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR14017:SF9. PTHR14017:SF9. 2 hits.
PfamiPF02373. JmjC. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS51184. JMJC. 1 hit.
PS50005. TPR. 7 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O15550-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSCGVSLAT AAAAAAAFGD EEKKMAAGKA SGESEEASPS LTAEEREALG
60 70 80 90 100
GLDSRLFGFV RFHEDGARTK ALLGKAVRCY ESLILKAEGK VESDFFCQLG
110 120 130 140 150
HFNLLLEDYP KALSAYQRYY SLQSDYWKNA AFLYGLGLVY FHYNAFQWAI
160 170 180 190 200
KAFQEVLYVD PSFCRAKEIH LRLGLMFKVN TDYESSLKHF QLALVDCNPC
210 220 230 240 250
TLSNAEIQFH IAHLYETQRK YHSAKEAYEQ LLQTENLSAQ VKATVLQQLG
260 270 280 290 300
WMHHTVDLLG DKATKESYAI QYLQKSLEAD PNSGQSWYFL GRCYSSIGKV
310 320 330 340 350
QDAFISYRQS IDKSEASADT WCSIGVLYQQ QNQPMDALQA YICAVQLDHG
360 370 380 390 400
HAAAWMDLGT LYESCNQPQD AIKCYLNATR SKSCSNTSAL AARIKYLQAQ
410 420 430 440 450
LCNLPQGSLQ NKTKLLPSIE EAWSLPIPAE LTSRQGAMNT AQQNTSDNWS
460 470 480 490 500
GGHAVSHPPV QQQAHSWCLT PQKLQHLEQL RANRNNLNPA QKLMLEQLES
510 520 530 540 550
QFVLMQQHQM RPTGVAQVRS TGIPNGPTAD SSLPTNSVSG QQPQLALTRV
560 570 580 590 600
PSVSQPGVRP ACPGQPLANG PFSAGHVPCS TSRTLGSTDT ILIGNNHITG
610 620 630 640 650
SGSNGNVPYL QRNALTLPHN RTNLTSSAEE PWKNQLSNST QGLHKGQSSH
660 670 680 690 700
SAGPNGERPL SSTGPSQHLQ AAGSGIQNQN GHPTLPSNSV TQGAALNHLS
710 720 730 740 750
SHTATSGGQQ GITLTKESKP SGNILTVPET SRHTGETPNS TASVEGLPNH
760 770 780 790 800
VHQMTADAVC SPSHGDSKSP GLLSSDNPQL SALLMGKANN NVGTGTCDKV
810 820 830 840 850
NNIHPAVHTK TDNSVASSPS SAISTATPSP KSTEQTTTNS VTSLNSPHSG
860 870 880 890 900
LHTINGEGME ESQSPMKTDL LLVNHKPSPQ IIPSMSVSIY PSSAEVLKAC
910 920 930 940 950
RNLGKNGLSN SSILLDKCPP PRPPSSPYPP LPKDKLNPPT PSIYLENKRD
960 970 980 990 1000
AFFPPLHQFC TNPNNPVTVI RGLAGALKLD LGLFSTKTLV EANNEHMVEV
1010 1020 1030 1040 1050
RTQLLQPADE NWDPTGTKKI WHCESNRSHT TIAKYAQYQA SSFQESLREE
1060 1070 1080 1090 1100
NEKRSHHKDH SDSESTSSDN SGRRRKGPFK TIKFGTNIDL SDDKKWKLQL
1110 1120 1130 1140 1150
HELTKLPAFV RVVSAGNLLS HVGHTILGMN TVQLYMKVPG SRTPGHQENN
1160 1170 1180 1190 1200
NFCSVNINIG PGDCEWFVVP EGYWGVLNDF CEKNNLNFLM GSWWPNLEDL
1210 1220 1230 1240 1250
YEANVPVYRF IQRPGDLVWI NAGTVHWVQA IGWCNNIAWN VGPLTACQYK
1260 1270 1280 1290 1300
LAVERYEWNK LQSVKSIVPM VHLSWNMARN IKVSDPKLFE MIKYCLLRTL
1310 1320 1330 1340 1350
KQCQTLREAL IAAGKEIIWH GRTKEEPAHY CSICEVEVFD LLFVTNESNS
1360 1370 1380 1390 1400
RKTYIVHCQD CARKTSGNLE NFVVLEQYKM EDLMQVYDQF TLAPPLPSAS

S
Length:1,401
Mass (Da):154,177
Last modified:September 23, 2008 - v2
Checksum:i9DD7EA6C61E79229
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti173L → V in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti173L → V in AAC51840 (PubMed:9381176).Curated1
Sequence conflicti585L → R in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti585L → R in AAC51840 (PubMed:9381176).Curated1
Sequence conflicti601S → N in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti601S → N in AAC51840 (PubMed:9381176).Curated1
Sequence conflicti629E → K in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti629E → K in AAC51840 (PubMed:9381176).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01449230A → T.Corresponds to variant rs6529dbSNPEnsembl.1
Natural variantiVAR_067225270I → V in a patient with chronic myelomonocytic leukemia. 1 Publication1
Natural variantiVAR_014493497Q → H.Corresponds to variant rs6530dbSNPEnsembl.1
Natural variantiVAR_046527581T → A.Corresponds to variant rs34922269dbSNPEnsembl.1
Natural variantiVAR_020313726T → K.1 PublicationCorresponds to variant rs2230018dbSNPEnsembl.1
Natural variantiVAR_067226834E → D in a patient with chronic myelomonocytic leukemia. 1 Publication1
Natural variantiVAR_067227922R → K in a patient with chronic myelomonocytic leukemia. 1 Publication1
Natural variantiVAR_0358711106L → R in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000992 mRNA. Translation: AAC51839.1.
AF000993 mRNA. Translation: AAC51840.1.
AL133545, AC136488, AL138744 Genomic DNA. Translation: CAI40508.1.
AL138744, AC136488, AL133545 Genomic DNA. Translation: CAI41479.1.
CH471141 Genomic DNA. Translation: EAW59368.1.
BC093868 mRNA. Translation: AAH93868.1.
BC113381 mRNA. Translation: AAI13382.1.
CCDSiCCDS14265.1.
PIRiT02255.
RefSeqiNP_066963.2. NM_021140.3.
UniGeneiHs.522616.

Genome annotation databases

EnsembliENST00000377967; ENSP00000367203; ENSG00000147050.
GeneIDi7403.
KEGGihsa:7403.
UCSCiuc004dge.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000992 mRNA. Translation: AAC51839.1.
AF000993 mRNA. Translation: AAC51840.1.
AL133545, AC136488, AL138744 Genomic DNA. Translation: CAI40508.1.
AL138744, AC136488, AL133545 Genomic DNA. Translation: CAI41479.1.
CH471141 Genomic DNA. Translation: EAW59368.1.
BC093868 mRNA. Translation: AAH93868.1.
BC113381 mRNA. Translation: AAI13382.1.
CCDSiCCDS14265.1.
PIRiT02255.
RefSeqiNP_066963.2. NM_021140.3.
UniGeneiHs.522616.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AVRX-ray1.80A880-1401[»]
3AVSX-ray1.85A880-1401[»]
ProteinModelPortaliO15550.
SMRiO15550.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113246. 27 interactors.
DIPiDIP-46192N.
IntActiO15550. 13 interactors.
MINTiMINT-1188304.
STRINGi9606.ENSP00000367203.

Chemistry databases

BindingDBiO15550.
ChEMBLiCHEMBL2069164.
GuidetoPHARMACOLOGYi2684.

PTM databases

iPTMnetiO15550.
PhosphoSitePlusiO15550.

Polymorphism and mutation databases

BioMutaiKDM6A.

Proteomic databases

EPDiO15550.
MaxQBiO15550.
PaxDbiO15550.
PeptideAtlasiO15550.
PRIDEiO15550.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377967; ENSP00000367203; ENSG00000147050.
GeneIDi7403.
KEGGihsa:7403.
UCSCiuc004dge.5. human.

Organism-specific databases

CTDi7403.
DisGeNETi7403.
GeneCardsiKDM6A.
GeneReviewsiKDM6A.
H-InvDBHIX0019137.
HGNCiHGNC:12637. KDM6A.
HPAiHPA000568.
HPA001165.
HPA002111.
MalaCardsiKDM6A.
MIMi300128. gene.
300867. phenotype.
neXtProtiNX_O15550.
OpenTargetsiENSG00000147050.
Orphaneti2322. Kabuki syndrome.
PharmGKBiPA37262.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
KOG1246. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00410000025758.
InParanoidiO15550.
KOiK11447.
PhylomeDBiO15550.
TreeFamiTF317405.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000147050-MONOMER.
ReactomeiR-HSA-3214842. HDMs demethylate histones.
R-HSA-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.

Miscellaneous databases

ChiTaRSiKDM6A. human.
GeneWikiiUTX_(gene).
GenomeRNAii7403.
PROiO15550.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147050.
CleanExiHS_UTX.
ExpressionAtlasiO15550. baseline and differential.
GenevisibleiO15550. HS.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR003347. JmjC_dom.
IPR029517. KDM6A.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR14017:SF9. PTHR14017:SF9. 2 hits.
PfamiPF02373. JmjC. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS51184. JMJC. 1 hit.
PS50005. TPR. 7 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKDM6A_HUMAN
AccessioniPrimary (citable) accession number: O15550
Secondary accession number(s): Q52LL9, Q5JVQ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 23, 2008
Last modified: November 30, 2016
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Escapes X chromosome inactivation.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.