O60341 · KDM1A_HUMAN
- ProteinLysine-specific histone demethylase 1A
- GeneKDM1A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids852 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290).
Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412).
May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412).
Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795).
Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1 (PubMed:29691401).
Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331).
Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16079794, PubMed:16140033).
Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636).
Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281).
Catalytic activity
- 2 A + 2 H2O + N6,N6-dimethyl-L-lysyl4-[histone H3] = 2 AH2 + 2 formaldehyde + L-lysyl4-[histone H3]
Cofactor
Activity regulation
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
3 μM | H3 monomethyl-K4 | |||||
4.2 μM | H3 dimethyl-K4 | |||||
3.9 μM | H3 monomethyl-K4-monomethyl-K9 | |||||
17.5 μM | monomethyl-K4-acetyl-K9 |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 289 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 308 | FAD (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 310 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 316 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 332-333 | FAD (UniProtKB | ChEBI) | ||||
Sequence: MV | ||||||
Binding site | 801 | FAD (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 810-811 | FAD (UniProtKB | ChEBI) | ||||
Sequence: TV |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
The subsequence QLQEKHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLVKSKHRDLTALCKEYDE shows transcriptional repressor activity in a high-throughput recruitment assay.
Names & Taxonomy
Protein names
- Recommended nameLysine-specific histone demethylase 1A
- EC number
- Alternative names
Gene names
- Community suggested namesKDM1A
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO60341
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Cleft palate, psychomotor retardation, and distinctive facial features (CPRF)
- Note
- DescriptionA syndrome characterized by cleft palate, developmental delay, psychomotor retardation, and facial dysmorphic features including a prominent forehead, slightly arched eyebrows, elongated palpebral fissures, a wide nasal bridge, thin lips, and widely spaced teeth. Cleft palate is a congenital fissure of the soft and/or hard palate, due to faulty fusion.
- See alsoMIM:616728
Natural variants in CPRF
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_076366 | 379 | E>K | in CPRF; dbSNP:rs864309715 | |
VAR_076367 | 556 | D>G | in CPRF; dbSNP:rs864309716 | |
VAR_076368 | 761 | Y>H | in CPRF; dbSNP:rs864309714 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_076366 | 379 | in CPRF; dbSNP:rs864309715 | |||
Sequence: E → K | ||||||
Mutagenesis | 432-436 | Mimics acetylation; preventing association with chromatin. | ||||
Sequence: KKIVK → QQIVQ | ||||||
Mutagenesis | 432-436 | Abolished acetylation by KAT8, promoting association with chromatin. | ||||
Sequence: KKIVK → RRIVR | ||||||
Mutagenesis | 503 | Loss of polyubiquitination. | ||||
Sequence: K → R | ||||||
Mutagenesis | 535 | Strongly reduces demethylase activity. | ||||
Sequence: N → A | ||||||
Natural variant | VAR_076367 | 556 | in CPRF; dbSNP:rs864309716 | |||
Sequence: D → G | ||||||
Mutagenesis | 564 | Strongly reduces demethylase activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 661 | Abolishes histone demethylase activity. | ||||
Sequence: K → A | ||||||
Natural variant | VAR_076368 | 761 | in CPRF; dbSNP:rs864309714 | |||
Sequence: Y → H | ||||||
Mutagenesis | 761 | Strongly reduces demethylase activity. | ||||
Sequence: Y → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 690 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), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000099881 | 1-852 | UniProt | Lysine-specific histone demethylase 1A | |||
Sequence: MLSGKKAAAAAAAAAAAATGTEAGPGTAGGSENGSEVAAQPAGLSGPAEVGPGAVGERTPRKKEPPRASPPGGLAEPPGSAGPQAGPTVVPGSATPMETGIAETPEGRRTSRRKRAKVEYREMDESLANLSEDEYYSEEERNAKAEKEKKLPPPPPQAPPEEENESEPEEPSGVEGAAFQSRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTFEATLQQLEAPYNSDTVLVHRVHSYLERHGLINFGIYKRIKPLPTKKTGKVIIIGSGVSGLAAARQLQSFGMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKCPLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQEKHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFANATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVRQVRYTASGCEVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLNKVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISDDVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGNDYDLMAQPITPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQATPGVPAQQSPSM | |||||||
Modified residue | 59 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 69 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 80 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 95 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 104 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 104 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 126 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 126 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 131 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 131 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 135 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 137 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 137 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 166 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 166 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 172 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 432 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 433 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 436 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Cross-link | 442 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 469 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 503 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue | 611 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 841 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 849 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 849 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 851 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Acetylation by KAT8 reduces KDM1A association with nucleosomes, thereby decreasing histone H3 demethylation, leading to transcription activatio of target genes (PubMed:27292636).
Deubiquitinated by USP38; preventing it from degradation by the 26S proteasome (PubMed:30497519).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of a RCOR/GFI/KDM1A/HDAC complex (PubMed:11102443, PubMed:12032298).
Interacts directly with GFI1 and GFI1B. Interacts with INSM1 (via N-terminus) (PubMed:23721412).
Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (PubMed:12493763, PubMed:16140033, PubMed:16885027).
In the complex, RCOR1/CoREST strongly enhances the demethylase activity and protects it from the proteasome while PHF21A/BHC80 inhibits the demethylase activity (PubMed:16079794, PubMed:16956976).
Interacts with the androgen receptor (AR) (PubMed:16079795).
Interacts with SNAI1 (via SNAG domain) (PubMed:20389281, PubMed:20562920, PubMed:21300290, PubMed:23721412).
Interacts (via AOD/Tower domain) with JADE2 (via C-terminus) (PubMed:25018020).
Interacts with ESRRB; co-occupes the core set of ESRRB targets (By similarity).
Interacts with SAMD1 (via WH domain); the interaction modulates KDM1A function (PubMed:33980486).
Interacts with RBPJ (PubMed:29030483).
Interacts with L3MBTL3 (PubMed:29030483).
Interacts with ZMYND8 (PubMed:25593309).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, coiled coil, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-176 | Disordered | ||||
Sequence: MLSGKKAAAAAAAAAAAATGTEAGPGTAGGSENGSEVAAQPAGLSGPAEVGPGAVGERTPRKKEPPRASPPGGLAEPPGSAGPQAGPTVVPGSATPMETGIAETPEGRRTSRRKRAKVEYREMDESLANLSEDEYYSEEERNAKAEKEKKLPPPPPQAPPEEENESEPEEPSGVEG | ||||||
Compositional bias | 105-151 | Basic and acidic residues | ||||
Sequence: PEGRRTSRRKRAKVEYREMDESLANLSEDEYYSEEERNAKAEKEKKL | ||||||
Coiled coil | 110-151 | |||||
Sequence: TSRRKRAKVEYREMDESLANLSEDEYYSEEERNAKAEKEKKL | ||||||
Domain | 174-273 | SWIRM | ||||
Sequence: VEGAAFQSRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTFEATLQQLEAPYNSDTVLVHRVHSYLERHGLINFGIYKRIKPL | ||||||
Region | 300-852 | Demethylase activity | ||||
Sequence: FGMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKCPLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQEKHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFANATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVRQVRYTASGCEVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLNKVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISDDVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGNDYDLMAQPITPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQATPGVPAQQSPSM | ||||||
Coiled coil | 428-514 | |||||
Sequence: IEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEAN |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O60341-1
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.
- Name1
- Length852
- Mass (Da)92,903
- Last updated2004-08-16 v2
- ChecksumA61CEDE51E4E0C1D
O60341-2
- Name2
Computationally mapped potential isoform sequences
There are 20 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I5QJJ5 | A0A8I5QJJ5_HUMAN | KDM1A | 790 | ||
A0A8I5QKM3 | A0A8I5QKM3_HUMAN | KDM1A | 794 | ||
A0A8I5QJX1 | A0A8I5QJX1_HUMAN | KDM1A | 229 | ||
A0A8I5QJR3 | A0A8I5QJR3_HUMAN | KDM1A | 729 | ||
R4GMQ1 | R4GMQ1_HUMAN | KDM1A | 858 | ||
R4GMP9 | R4GMP9_HUMAN | KDM1A | 301 | ||
A0A8I5KPV0 | A0A8I5KPV0_HUMAN | KDM1A | 586 | ||
A0A8I5KRX9 | A0A8I5KRX9_HUMAN | KDM1A | 757 | ||
A0A8I5KSH0 | A0A8I5KSH0_HUMAN | KDM1A | 802 | ||
A0A8I5KSI8 | A0A8I5KSI8_HUMAN | KDM1A | 196 | ||
A0A8I5KQU6 | A0A8I5KQU6_HUMAN | KDM1A | 700 | ||
A0A8I5KRF4 | A0A8I5KRF4_HUMAN | KDM1A | 684 | ||
A0A8I5KRB8 | A0A8I5KRB8_HUMAN | KDM1A | 774 | ||
A0A8I5KRC9 | A0A8I5KRC9_HUMAN | KDM1A | 566 | ||
A0A8I5KTR5 | A0A8I5KTR5_HUMAN | KDM1A | 582 | ||
A0A8I5KT29 | A0A8I5KT29_HUMAN | KDM1A | 771 | ||
A0A8I5KVZ4 | A0A8I5KVZ4_HUMAN | KDM1A | 820 | ||
A0A8I5KUU0 | A0A8I5KUU0_HUMAN | KDM1A | 249 | ||
A0A8I5KV76 | A0A8I5KV76_HUMAN | KDM1A | 840 | ||
A0A8I5KXU4 | A0A8I5KXU4_HUMAN | KDM1A | 878 |
Sequence caution
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 78 | in Ref. 3; AAH40194 | ||||
Sequence: P → Q | ||||||
Compositional bias | 105-151 | Basic and acidic residues | ||||
Sequence: PEGRRTSRRKRAKVEYREMDESLANLSEDEYYSEEERNAKAEKEKKL | ||||||
Alternative sequence | VSP_011198 | 173 | in isoform 2 | |||
Sequence: G → GQAGGLQDDSSGGYGDGQASG | ||||||
Alternative sequence | VSP_011199 | 369 | in isoform 2 | |||
Sequence: A → ADTVK | ||||||
Sequence conflict | 405 | in Ref. 3; AAH48134 | ||||
Sequence: P → H | ||||||
Sequence conflict | 669 | in Ref. 4; CAD38675 | ||||
Sequence: V → A | ||||||
Sequence conflict | 814 | in Ref. 3; AAH16639 | ||||
Sequence: A → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB011173 EMBL· GenBank· DDBJ | BAA25527.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AL031428 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC016639 EMBL· GenBank· DDBJ | AAH16639.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025362 EMBL· GenBank· DDBJ | AAH25362.1 EMBL· GenBank· DDBJ | mRNA | ||
BC040194 EMBL· GenBank· DDBJ | AAH40194.3 EMBL· GenBank· DDBJ | mRNA | ||
BC048134 EMBL· GenBank· DDBJ | AAH48134.2 EMBL· GenBank· DDBJ | mRNA | ||
AL833812 EMBL· GenBank· DDBJ | CAD38675.2 EMBL· GenBank· DDBJ | mRNA |