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Protein

Lysine-specific demethylase 6A

Gene

Kdm6a

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi1146 – 11461IronBy similarity
Metal bindingi1148 – 11481IronBy similarity
Metal bindingi1226 – 12261IronBy similarity
Metal bindingi1331 – 13311ZincBy similarity
Metal bindingi1334 – 13341ZincBy similarity
Metal bindingi1358 – 13581ZincBy similarity
Metal bindingi1361 – 13611ZincBy similarity

GO - Molecular functioni

  • chromatin DNA binding Source: MGI
  • dioxygenase activity Source: UniProtKB-KW
  • histone demethylase activity (H3-K27 specific) Source: MGI
  • identical protein binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI

GO - Biological processi

  • canonical Wnt signaling pathway Source: MGI
  • cardiovascular system development Source: MGI
  • embryonic organ development Source: MGI
  • heart development Source: MGI
  • heart morphogenesis Source: MGI
  • histone H3-K27 demethylation Source: MGI
  • in utero embryonic development Source: MGI
  • mesodermal cell differentiation Source: MGI
  • multicellular organism growth Source: MGI
  • neural tube closure Source: MGI
  • neural tube development Source: MGI
  • notochord morphogenesis Source: MGI
  • positive regulation of gene expression Source: MGI
  • regulation of gene expression Source: MGI
  • respiratory system process Source: MGI
  • somite rostral/caudal axis specification Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3214842. HDMs demethylate histones.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1095419. Kdm6a.

Subcellular locationi

GO - Cellular componenti

  • histone methyltransferase complex Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14011401Lysine-specific demethylase 6APRO_0000106410Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei769 – 7691PhosphoserineCombined sources
Modified residuei827 – 8271PhosphothreonineCombined sources
Modified residuei829 – 8291PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO70546.
MaxQBiO70546.
PaxDbiO70546.
PRIDEiO70546.

PTM databases

iPTMnetiO70546.
PhosphoSiteiO70546.

Expressioni

Tissue specificityi

Expressed in brain, heart and spleen.

Developmental stagei

Widely expressed at E13.5.

Gene expression databases

BgeeiO70546.
GenevisibleiO70546. MM.

Interactioni

Subunit structurei

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 (By similarity). Interacts with TLE1. Interacts with SUPT6H.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Six4Q613212EBI-1573712,EBI-986524

GO - Molecular functioni

  • identical protein binding Source: MGI

Protein-protein interaction databases

BioGridi204471. 3 interactions.
IntActiO70546. 5 interactions.
MINTiMINT-4584348.
STRINGi10090.ENSMUSP00000061539.

Structurei

3D structure databases

ProteinModelPortaliO70546.
SMRiO70546. Positions 886-1395.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati95 – 12834TPR 1Add
BLAST
Repeati132 – 16534TPR 2Add
BLAST
Repeati169 – 20335TPR 3Add
BLAST
Repeati207 – 24034TPR 4Add
BLAST
Repeati245 – 28541TPR 5Add
BLAST
Repeati286 – 31934TPR 6Add
BLAST
Repeati321 – 35333TPR 7Add
BLAST
Repeati355 – 38733TPR 8Add
BLAST
Domaini1095 – 1258164JmjCPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 10951095Interaction with SUPT6HAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi9 – 1911Poly-AlaAdd
BLAST
Compositional biasi919 – 94123Pro-richAdd
BLAST

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.
HOGENOMiHOG000220834.
InParanoidiO70546.
KOiK11447.
OMAiCLEEYRL.
OrthoDBiEOG7CG6Z5.
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. 2 hits.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 5 hits.
PROSITEiPS51184. JMJC. 1 hit.
PS50005. TPR. 7 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O70546-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKSCGVSLAT AAAAAAAAAF GDEEKKMAAG KASGESEEAS PSLTAEEREA
60 70 80 90 100
LGGLDSRLFG FVRFHEDGAR MKALLGKAVR CYESLILKAE GKVESDFFCQ
110 120 130 140 150
LGHFNLLLED YPKALSAYQR YYSLQSDYWK NAAFLYGLGL VYFHYNAFQW
160 170 180 190 200
AIKAFQEVLY VDPSFCRAKE IHLRLGLMFK VNTDYESSLK HFQLALVDCN
210 220 230 240 250
PCTLSNAEIQ FHIAHLYETQ RKYHSAKEAY EQLLQTENLS AQVKATILQQ
260 270 280 290 300
LGWMHHTVDL LGDKATKESY AIQYLQKSLE ADPNSGQSWY FLGRCYSSIG
310 320 330 340 350
KVQDAFISYR QSIDKSEASA DTWCSIGVLY QQQNQPMDAL QAYICAVQLD
360 370 380 390 400
HGHAAAWMDL GTLYESCNQP QDAIKCYLNA TRSKNCSNTS GLAARIKYLQ
410 420 430 440 450
AQLCNLPQGS LQNKTKLLPS IEEAWSLPIP AELTSRQGAM NTAQQNTSDN
460 470 480 490 500
WSGGNAPPPV EQQTHSWCLT PQKLQHLEQL RANRNNLNPA QKLMLEQLES
510 520 530 540 550
QFVLMQQHQM RQTGVAQVRP TGILNGPTVD SSLPTNSVSG QQPQLPLTRM
560 570 580 590 600
PSVSQPGVHT ACPRQTLANG PFSAGHVPCS TSRTLGSTDT VLIGNNHVTG
610 620 630 640 650
SGSNGNVPYL QRNAPTLPHN RTNLTSSTEE PWKNQLSNST QGLHKGPSSH
660 670 680 690 700
LAGPNGERPL SSTGPSQHLQ AAGSGIQNQN GHPTLPSNSV TQGAALNHLS
710 720 730 740 750
SHTATSGGQQ GITLTKESKP SGNTLTVPET SRQTGETPNS TASVEGLPNH
760 770 780 790 800
VHQVMADAVC SPSHGDSKSP GLLSSDNPQL SALLMGKANN NVGPGTCDKV
810 820 830 840 850
NNIHPTVHTK TDNSVASSPS SAISTATPSP KSTEQTTTNS VTSLNSPHSG
860 870 880 890 900
LHTINGEGME ESQSPIKTDL LLVSHRPSPQ 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 SGKRRKGPFK 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 LQNVKSIVPM 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):154,355
Last modified:January 9, 2007 - v2
Checksum:i293DA417F49EECFF
GO
Isoform 2 (identifier: O70546-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1393-1401: APPLPSASS → VSEINMLLHYHPPHLDIVPWTLNMRPFLLFRK

Show »
Length:1,424
Mass (Da):157,458
Checksum:iFD83D03980684B3C
GO

Sequence cautioni

The sequence AAH75703.1 differs from that shown.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti321 – 3211D → G in AAH75703 (PubMed:15489334).Curated
Sequence conflicti1198 – 11981E → G in AAH75703 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1393 – 14019APPLPSASS → VSEINMLLHYHPPHLDIVPW TLNMRPFLLFRK in isoform 2. 1 PublicationVSP_022196

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL732451, AL773547 Genomic DNA. Translation: CAM27157.1.
AL773547, AL732451 Genomic DNA. Translation: CAM18408.1.
BC053433 mRNA. Translation: AAH53433.1.
BC075703 mRNA. Translation: AAH75703.1. Different initiation.
AJ002730 mRNA. Translation: CAA05692.1.
CCDSiCCDS30037.1. [O70546-2]
CCDS81102.1. [O70546-1]
RefSeqiNP_001297373.1. NM_001310444.1. [O70546-1]
NP_033509.1. NM_009483.2. [O70546-2]
UniGeneiMm.257498.
Mm.417709.

Genome annotation databases

EnsembliENSMUST00000044484; ENSMUSP00000045862; ENSMUSG00000037369. [O70546-1]
ENSMUST00000052368; ENSMUSP00000061539; ENSMUSG00000037369. [O70546-2]
GeneIDi22289.
KEGGimmu:22289.
UCSCiuc009ssk.1. mouse. [O70546-1]
uc009ssm.1. mouse. [O70546-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL732451, AL773547 Genomic DNA. Translation: CAM27157.1.
AL773547, AL732451 Genomic DNA. Translation: CAM18408.1.
BC053433 mRNA. Translation: AAH53433.1.
BC075703 mRNA. Translation: AAH75703.1. Different initiation.
AJ002730 mRNA. Translation: CAA05692.1.
CCDSiCCDS30037.1. [O70546-2]
CCDS81102.1. [O70546-1]
RefSeqiNP_001297373.1. NM_001310444.1. [O70546-1]
NP_033509.1. NM_009483.2. [O70546-2]
UniGeneiMm.257498.
Mm.417709.

3D structure databases

ProteinModelPortaliO70546.
SMRiO70546. Positions 886-1395.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204471. 3 interactions.
IntActiO70546. 5 interactions.
MINTiMINT-4584348.
STRINGi10090.ENSMUSP00000061539.

PTM databases

iPTMnetiO70546.
PhosphoSiteiO70546.

Proteomic databases

EPDiO70546.
MaxQBiO70546.
PaxDbiO70546.
PRIDEiO70546.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000044484; ENSMUSP00000045862; ENSMUSG00000037369. [O70546-1]
ENSMUST00000052368; ENSMUSP00000061539; ENSMUSG00000037369. [O70546-2]
GeneIDi22289.
KEGGimmu:22289.
UCSCiuc009ssk.1. mouse. [O70546-1]
uc009ssm.1. mouse. [O70546-2]

Organism-specific databases

CTDi7403.
MGIiMGI:1095419. Kdm6a.

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
KOG1246. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00410000025758.
HOGENOMiHOG000220834.
InParanoidiO70546.
KOiK11447.
OMAiCLEEYRL.
OrthoDBiEOG7CG6Z5.
TreeFamiTF317405.

Enzyme and pathway databases

ReactomeiR-MMU-3214842. HDMs demethylate histones.

Miscellaneous databases

ChiTaRSiKdm6a. mouse.
NextBioi302431.
PROiO70546.
SOURCEiSearch...

Gene expression databases

BgeeiO70546.
GenevisibleiO70546. MM.

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. 2 hits.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 5 hits.
PROSITEiPS51184. JMJC. 1 hit.
PS50005. TPR. 7 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 255-1401 (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Embryonic germ cell and Limb.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 69-1401 (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Embryo.
  4. "Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms."
    Grbavec D., Lo R., Liu Y., Greenfield A., Stifani S.
    Biochem. J. 337:13-17(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TLE1.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic brain.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-769; THR-827 AND SER-829, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Kidney, Lung and Spleen.
  7. "The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis."
    Wang A.H., Zare H., Mousavi K., Wang C., Moravec C.E., Sirotkin H.I., Ge K., Gutierrez-Cruz G., Sartorelli V.
    EMBO J. 32:1075-1086(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SUPT6H.

Entry informationi

Entry nameiKDM6A_MOUSE
AccessioniPrimary (citable) accession number: O70546
Secondary accession number(s): A2AID2, Q6DI80, Q7TSG4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 9, 2007
Last modified: May 11, 2016
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Escapes X chromosome inactivation.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.