O15550 · KDM6A_HUMAN
- ProteinLysine-specific demethylase 6A
- GeneKDM6A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1401 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17761849, PubMed:17851529).
Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17713478, PubMed:17761849, PubMed:17851529).
Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529).
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 (PubMed:17761849).
Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity).
Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17713478, PubMed:17761849, PubMed:17851529).
Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529).
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 (PubMed:17761849).
Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity).
Miscellaneous
Escapes X chromosome inactivation.
Catalytic activity
- 2 2-oxoglutarate + N6,N6,N6-trimethyl-L-lysyl27-[histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + N6-methyl-L-lysyl27-[histone H3] + 2 succinate
2 CHEBI:16810 + RHEA-COMP:15535 CHEBI:61961 Position: 27+ 2 CHEBI:15379 = 2 CHEBI:16526 + 2 CHEBI:16842 + RHEA-COMP:15544 CHEBI:61929 Position: 27+ 2 CHEBI:30031
Cofactor
Protein has several cofactor binding sites:
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 1146 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1148 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 1226 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1331 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1334 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1358 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1361 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | histone methyltransferase complex | |
Cellular Component | MLL3/4 complex | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | chromatin DNA binding | |
Molecular Function | histone demethylase activity | |
Molecular Function | histone H3K27me2/H3K27me3 demethylase activity | |
Molecular Function | metal ion binding | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Biological Process | chromatin remodeling | |
Biological Process | regulation of gene expression |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLysine-specific demethylase 6A
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO15550
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Kabuki syndrome 2 (KABUK2)
- Note
- DescriptionA congenital intellectual disability 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 alsoMIM:300867
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_014492 | 30 | in dbSNP:rs6529 | |||
Sequence: A → T | ||||||
Natural variant | VAR_067225 | 270 | in a patient with chronic myelomonocytic leukemia | |||
Sequence: I → V | ||||||
Natural variant | VAR_014493 | 497 | in dbSNP:rs6530 | |||
Sequence: Q → H | ||||||
Natural variant | VAR_046527 | 581 | in dbSNP:rs34922269 | |||
Sequence: T → A | ||||||
Natural variant | VAR_020313 | 726 | in dbSNP:rs2230018 | |||
Sequence: T → K | ||||||
Natural variant | VAR_067226 | 834 | in a patient with chronic myelomonocytic leukemia; dbSNP:rs2148052943 | |||
Sequence: E → D | ||||||
Natural variant | VAR_067227 | 922 | in a patient with chronic myelomonocytic leukemia; dbSNP:rs2148101953 | |||
Sequence: R → K | ||||||
Natural variant | VAR_035871 | 1106 | in a colorectal cancer sample; somatic mutation | |||
Sequence: L → R | ||||||
Mutagenesis | 1146 | Abolishes histone demethylase activity. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4,017 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000106409 | 1-1401 | UniProt | Lysine-specific demethylase 6A | |||
Sequence: MKSCGVSLATAAAAAAAFGDEEKKMAAGKASGESEEASPSLTAEEREALGGLDSRLFGFVRFHEDGARTKALLGKAVRCYESLILKAEGKVESDFFCQLGHFNLLLEDYPKALSAYQRYYSLQSDYWKNAAFLYGLGLVYFHYNAFQWAIKAFQEVLYVDPSFCRAKEIHLRLGLMFKVNTDYESSLKHFQLALVDCNPCTLSNAEIQFHIAHLYETQRKYHSAKEAYEQLLQTENLSAQVKATVLQQLGWMHHTVDLLGDKATKESYAIQYLQKSLEADPNSGQSWYFLGRCYSSIGKVQDAFISYRQSIDKSEASADTWCSIGVLYQQQNQPMDALQAYICAVQLDHGHAAAWMDLGTLYESCNQPQDAIKCYLNATRSKSCSNTSALAARIKYLQAQLCNLPQGSLQNKTKLLPSIEEAWSLPIPAELTSRQGAMNTAQQNTSDNWSGGHAVSHPPVQQQAHSWCLTPQKLQHLEQLRANRNNLNPAQKLMLEQLESQFVLMQQHQMRPTGVAQVRSTGIPNGPTADSSLPTNSVSGQQPQLALTRVPSVSQPGVRPACPGQPLANGPFSAGHVPCSTSRTLGSTDTILIGNNHITGSGSNGNVPYLQRNALTLPHNRTNLTSSAEEPWKNQLSNSTQGLHKGQSSHSAGPNGERPLSSTGPSQHLQAAGSGIQNQNGHPTLPSNSVTQGAALNHLSSHTATSGGQQGITLTKESKPSGNILTVPETSRHTGETPNSTASVEGLPNHVHQMTADAVCSPSHGDSKSPGLLSSDNPQLSALLMGKANNNVGTGTCDKVNNIHPAVHTKTDNSVASSPSSAISTATPSPKSTEQTTTNSVTSLNSPHSGLHTINGEGMEESQSPMKTDLLLVNHKPSPQIIPSMSVSIYPSSAEVLKACRNLGKNGLSNSSILLDKCPPPRPPSSPYPPLPKDKLNPPTPSIYLENKRDAFFPPLHQFCTNPNNPVTVIRGLAGALKLDLGLFSTKTLVEANNEHMVEVRTQLLQPADENWDPTGTKKIWHCESNRSHTTIAKYAQYQASSFQESLREENEKRSHHKDHSDSESTSSDNSGRRRKGPFKTIKFGTNIDLSDDKKWKLQLHELTKLPAFVRVVSAGNLLSHVGHTILGMNTVQLYMKVPGSRTPGHQENNNFCSVNINIGPGDCEWFVVPEGYWGVLNDFCEKNNLNFLMGSWWPNLEDLYEANVPVYRFIQRPGDLVWINAGTVHWVQAIGWCNNIAWNVGPLTACQYKLAVERYEWNKLQSVKSIVPMVHLSWNMARNIKVSDPKLFEMIKYCLLRTLKQCQTLREALIAAGKEIIWHGRTKEEPAHYCSICEVEVFDLLFVTNESNSRKTYIVHCQDCARKTSGNLENFVVLEQYKMEDLMQVYDQFTLAPPLPSASS | |||||||
Modified residue | 519 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue | 549 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue (large scale data) | 761 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 769 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 769 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 817 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 818 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 827 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 827 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 829 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 829 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1061 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
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 (PubMed:17500065, PubMed:17713478).
Interacts with SUPT6H. Interacts with SMARCA4 (By similarity).
Interacts with PROSER1 (PubMed:34667079).
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 (PubMed:17500065, PubMed:17713478).
Interacts with SUPT6H. Interacts with SMARCA4 (By similarity).
Interacts with PROSER1 (PubMed:34667079).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O15550 | GSC2 O15499 | 3 | EBI-4292203, EBI-19954058 | |
BINARY | O15550 | MEOX2 Q6FHY5 | 3 | EBI-4292203, EBI-16439278 | |
BINARY | O15550 | WDR5 P61964 | 7 | EBI-4292203, EBI-540834 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-1095 | Interaction with SUPT6H | ||||
Sequence: MKSCGVSLATAAAAAAAFGDEEKKMAAGKASGESEEASPSLTAEEREALGGLDSRLFGFVRFHEDGARTKALLGKAVRCYESLILKAEGKVESDFFCQLGHFNLLLEDYPKALSAYQRYYSLQSDYWKNAAFLYGLGLVYFHYNAFQWAIKAFQEVLYVDPSFCRAKEIHLRLGLMFKVNTDYESSLKHFQLALVDCNPCTLSNAEIQFHIAHLYETQRKYHSAKEAYEQLLQTENLSAQVKATVLQQLGWMHHTVDLLGDKATKESYAIQYLQKSLEADPNSGQSWYFLGRCYSSIGKVQDAFISYRQSIDKSEASADTWCSIGVLYQQQNQPMDALQAYICAVQLDHGHAAAWMDLGTLYESCNQPQDAIKCYLNATRSKSCSNTSALAARIKYLQAQLCNLPQGSLQNKTKLLPSIEEAWSLPIPAELTSRQGAMNTAQQNTSDNWSGGHAVSHPPVQQQAHSWCLTPQKLQHLEQLRANRNNLNPAQKLMLEQLESQFVLMQQHQMRPTGVAQVRSTGIPNGPTADSSLPTNSVSGQQPQLALTRVPSVSQPGVRPACPGQPLANGPFSAGHVPCSTSRTLGSTDTILIGNNHITGSGSNGNVPYLQRNALTLPHNRTNLTSSAEEPWKNQLSNSTQGLHKGQSSHSAGPNGERPLSSTGPSQHLQAAGSGIQNQNGHPTLPSNSVTQGAALNHLSSHTATSGGQQGITLTKESKPSGNILTVPETSRHTGETPNSTASVEGLPNHVHQMTADAVCSPSHGDSKSPGLLSSDNPQLSALLMGKANNNVGTGTCDKVNNIHPAVHTKTDNSVASSPSSAISTATPSPKSTEQTTTNSVTSLNSPHSGLHTINGEGMEESQSPMKTDLLLVNHKPSPQIIPSMSVSIYPSSAEVLKACRNLGKNGLSNSSILLDKCPPPRPPSSPYPPLPKDKLNPPTPSIYLENKRDAFFPPLHQFCTNPNNPVTVIRGLAGALKLDLGLFSTKTLVEANNEHMVEVRTQLLQPADENWDPTGTKKIWHCESNRSHTTIAKYAQYQASSFQESLREENEKRSHHKDHSDSESTSSDNSGRRRKGPFKTIKFGTNIDLSDDKK | ||||||
Repeat | 93-126 | TPR 1 | ||||
Sequence: SDFFCQLGHFNLLLEDYPKALSAYQRYYSLQSDY | ||||||
Repeat | 130-163 | TPR 2 | ||||
Sequence: AAFLYGLGLVYFHYNAFQWAIKAFQEVLYVDPSF | ||||||
Repeat | 170-199 | TPR 3 | ||||
Sequence: HLRLGLMFKVNTDYESSLKHFQLALVDCNP | ||||||
Repeat | 205-238 | TPR 4 | ||||
Sequence: AEIQFHIAHLYETQRKYHSAKEAYEQLLQTENLS | ||||||
Repeat | 250-283 | TPR 5 | ||||
Sequence: GWMHHTVDLLGDKATKESYAIQYLQKSLEADPNS | ||||||
Repeat | 284-317 | TPR 6 | ||||
Sequence: GQSWYFLGRCYSSIGKVQDAFISYRQSIDKSEAS | ||||||
Repeat | 318-351 | TPR 7 | ||||
Sequence: ADTWCSIGVLYQQQNQPMDALQAYICAVQLDHGH | ||||||
Repeat | 352-385 | TPR 8 | ||||
Sequence: AAAWMDLGTLYESCNQPQDAIKCYLNATRSKSCS | ||||||
Region | 437-457 | Disordered | ||||
Sequence: AMNTAQQNTSDNWSGGHAVSH | ||||||
Region | 521-541 | Disordered | ||||
Sequence: TGIPNGPTADSSLPTNSVSGQ | ||||||
Region | 624-746 | Disordered | ||||
Sequence: LTSSAEEPWKNQLSNSTQGLHKGQSSHSAGPNGERPLSSTGPSQHLQAAGSGIQNQNGHPTLPSNSVTQGAALNHLSSHTATSGGQQGITLTKESKPSGNILTVPETSRHTGETPNSTASVEG | ||||||
Region | 758-778 | Disordered | ||||
Sequence: AVCSPSHGDSKSPGLLSSDNP | ||||||
Compositional bias | 810-862 | Polar residues | ||||
Sequence: KTDNSVASSPSSAISTATPSPKSTEQTTTNSVTSLNSPHSGLHTINGEGMEES | ||||||
Region | 810-864 | Disordered | ||||
Sequence: KTDNSVASSPSSAISTATPSPKSTEQTTTNSVTSLNSPHSGLHTINGEGMEESQS | ||||||
Region | 914-940 | Disordered | ||||
Sequence: LLDKCPPPRPPSSPYPPLPKDKLNPPT | ||||||
Compositional bias | 917-937 | Pro residues | ||||
Sequence: KCPPPRPPSSPYPPLPKDKLN | ||||||
Region | 1043-1079 | Disordered | ||||
Sequence: FQESLREENEKRSHHKDHSDSESTSSDNSGRRRKGPF | ||||||
Compositional bias | 1046-1076 | Basic and acidic residues | ||||
Sequence: SLREENEKRSHHKDHSDSESTSSDNSGRRRK | ||||||
Domain | 1095-1258 | JmjC | ||||
Sequence: KWKLQLHELTKLPAFVRVVSAGNLLSHVGHTILGMNTVQLYMKVPGSRTPGHQENNNFCSVNINIGPGDCEWFVVPEGYWGVLNDFCEKNNLNFLMGSWWPNLEDLYEANVPVYRFIQRPGDLVWINAGTVHWVQAIGWCNNIAWNVGPLTACQYKLAVERYEW |
Sequence similarities
Belongs to the UTX family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,401
- Mass (Da)154,177
- Last updated2008-09-23 v2
- Checksum9DD7EA6C61E79229
Computationally mapped potential isoform sequences
There are 18 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A6Q8PFK0 | A0A6Q8PFK0_HUMAN | KDM6A | 1367 | ||
A0A6Q8PFD0 | A0A6Q8PFD0_HUMAN | KDM6A | 1256 | ||
A0A6Q8PG92 | A0A6Q8PG92_HUMAN | KDM6A | 1293 | ||
A0A6Q8PG32 | A0A6Q8PG32_HUMAN | KDM6A | 1355 | ||
A0A6Q8PGN0 | A0A6Q8PGN0_HUMAN | KDM6A | 1336 | ||
A0A6Q8PGG6 | A0A6Q8PGG6_HUMAN | KDM6A | 151 | ||
A0A6Q8PH94 | A0A6Q8PH94_HUMAN | KDM6A | 126 | ||
A0A6Q8PHJ0 | A0A6Q8PHJ0_HUMAN | KDM6A | 1129 | ||
A0A6Q8PHB6 | A0A6Q8PHB6_HUMAN | KDM6A | 1427 | ||
F8W8R6 | F8W8R6_HUMAN | KDM6A | 1408 | ||
H0Y6V5 | H0Y6V5_HUMAN | KDM6A | 161 | ||
A0A804HIZ7 | A0A804HIZ7_HUMAN | KDM6A | 142 | ||
A0A804HLJ3 | A0A804HLJ3_HUMAN | KDM6A | 842 | ||
A0A804HJA2 | A0A804HJA2_HUMAN | KDM6A | 1374 | ||
A0A087X0R0 | A0A087X0R0_HUMAN | KDM6A | 1453 | ||
A0A087WUN6 | A0A087WUN6_HUMAN | KDM6A | 224 | ||
F5H6S1 | F5H6S1_HUMAN | KDM6A | 1356 | ||
F5H5V6 | F5H5V6_HUMAN | KDM6A | 1322 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 173 | in Ref. 1; AAC51839/AAC51840 | ||||
Sequence: L → V | ||||||
Sequence conflict | 585 | in Ref. 1; AAC51839/AAC51840 | ||||
Sequence: L → R | ||||||
Sequence conflict | 601 | in Ref. 1; AAC51839/AAC51840 | ||||
Sequence: S → N | ||||||
Sequence conflict | 629 | in Ref. 1; AAC51839/AAC51840 | ||||
Sequence: E → K | ||||||
Compositional bias | 810-862 | Polar residues | ||||
Sequence: KTDNSVASSPSSAISTATPSPKSTEQTTTNSVTSLNSPHSGLHTINGEGMEES | ||||||
Compositional bias | 917-937 | Pro residues | ||||
Sequence: KCPPPRPPSSPYPPLPKDKLN | ||||||
Compositional bias | 1046-1076 | Basic and acidic residues | ||||
Sequence: SLREENEKRSHHKDHSDSESTSSDNSGRRRK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF000992 EMBL· GenBank· DDBJ | AAC51839.1 EMBL· GenBank· DDBJ | mRNA | ||
AF000993 EMBL· GenBank· DDBJ | AAC51840.1 EMBL· GenBank· DDBJ | mRNA | ||
AC136488 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL133545 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL138744 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471141 EMBL· GenBank· DDBJ | EAW59368.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC093868 EMBL· GenBank· DDBJ | AAH93868.1 EMBL· GenBank· DDBJ | mRNA | ||
BC113381 EMBL· GenBank· DDBJ | AAI13382.1 EMBL· GenBank· DDBJ | mRNA |