InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Kdm1a

Summary

InnateDB Protein

IDBP-274526.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Kdm1a

Protein Name

lysine (K)-specific demethylase 1A

Synonyms

1810043O07Rik; AA408884; Aof2; D4Ertd478e; Kdm1; Lsd1; mKIAA0601;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000111977

InnateDB Gene

IDBG-198084 (Kdm1a)

Protein Structure

UniProt Annotation

Function

Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. 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. 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. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-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. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation (By similarity). Demethylates and stabilizes the DNA methylase DNMT1. 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. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7. {ECO:0000250, ECO:0000269PubMed:17707228, ECO:0000269PubMed:19098913}.

Subcellular Localization

Nucleus {ECO:0000250}.

Disease Associations

Tissue Specificity

Ubiquitously expressed. {ECO:0000269PubMed:16079795}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 46 experimentally validated interaction(s) in this database.
They are also associated with 98 interaction(s) predicted by orthology.

Experimentally validated
Total	46 [view]
Protein-Protein	46 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	98 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001085	RNA polymerase II transcription factor binding
GO:0002039	p53 binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0016491	oxidoreductase activity
GO:0019899	enzyme binding
GO:0030374	ligand-dependent nuclear receptor transcription coactivator activity
GO:0032451	demethylase activity
GO:0032452	histone demethylase activity
GO:0032453	histone demethylase activity (H3-K4 specific)
GO:0032454	histone demethylase activity (H3-K9 specific)
GO:0034648	histone demethylase activity (H3-dimethyl-K4 specific)
GO:0043426	MRF binding
GO:0044212	transcription regulatory region DNA binding
GO:0050660	flavin adenine dinucleotide binding
GO:0050681	androgen receptor binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001701	in utero embryonic development
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006482	protein demethylation
GO:0008283	cell proliferation
GO:0010725	regulation of primitive erythrocyte differentiation
GO:0021983	pituitary gland development
GO:0030851	granulocyte differentiation
GO:0032091	negative regulation of protein binding
GO:0033169	histone H3-K9 demethylation
GO:0034401	regulation of transcription by chromatin organization
GO:0034720	histone H3-K4 demethylation
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator
GO:0045648	positive regulation of erythrocyte differentiation
GO:0045654	positive regulation of megakaryocyte differentiation
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046886	positive regulation of hormone biosynthetic process
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051572	negative regulation of histone H3-K4 methylation
GO:0051573	negative regulation of histone H3-K9 methylation
GO:0055001	muscle cell development
GO:0055114	oxidation-reduction process
GO:1902166	negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:2000179	positive regulation of neural precursor cell proliferation
GO:2000648	positive regulation of stem cell proliferation

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005667	transcription factor complex

Protein Structure and Domains

PDB ID

MGI:1196256

InterPro

IPR001327 Pyridine nucleotide-disulphide oxidoreductase, NAD-binding domain
IPR002937 Amine oxidase
IPR003953 FAD binding domain
IPR006076 FAD dependent oxidoreductase
IPR007526 SWIRM domain
IPR009057 Homeodomain-like
IPR017366 Histone lysine-specific demethylase

PFAM

PF00070
PF01593
PF00890
PF01266
PF04433

PRINTS

PIRSF

PIRSF038051

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q6ZQ88