InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Dnmt1

Summary

InnateDB Protein

IDBP-138143.6

Last Modified

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

Gene Symbol

Dnmt1

Protein Name

DNA methyltransferase (cytosine-5) 1

Synonyms

Cxxc9; Dnmt; Dnmt1o; m.MmuI; MCMT; Met-1; Met1; MommeD2; MTase;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000004202

InnateDB Gene

IDBG-138141 (Dnmt1)

Protein Structure

UniProt Annotation

Function

Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. {ECO:0000269PubMed:11290321, ECO:0000269PubMed:15550930, ECO:0000269PubMed:17576694}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:11290321}. Cytoplasm {ECO:0000269PubMed:11290321}. Note=It is nucleoplasmic through most of the cell cycle and associates with replication foci during S-phase. In germ cells, spermatogonia, preleptotene and leptotene spermatocytes all express high levels of nuclear protein, while the protein is not detected in pachytene spermatocytes, despite the fact they expressed high levels of mRNA. In females, the protein is not detected in non-growing oocytes, in contrast to the growing oocytes. During the growing, the protein is no longer detectable in nuclei but accumulates to very high levels first throughout the cytoplasm. At the time of ovulation, all the protein is cytoplasmic and is actively associated with the oocyte cortex. After fecondation, in the preimplantation embryo, the protein remains cytoplasmic and after implantation, it is exclusively nuclear in all tissue types. Isoform 2 is sequestered in the cytoplasm of maturing oocytes and of preimplantation embryos, except for the 8-cell stage, while isoform 1 is exclusively nuclear.

Disease Associations

Tissue Specificity

Isoform 1 is expressed in embryonic stem cells and in somatic tissues. Isoform 2 is expressed in oocytes, preimplantation embryos, testis and in skeletal muscle during myogenesis.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 40 experimentally validated interaction(s) in this database.
They are also associated with 96 interaction(s) predicted by orthology.

Experimentally validated
Total	40 [view]
Protein-Protein	36 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	96 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003723	RNA binding
GO:0003886	DNA (cytosine-5-)-methyltransferase activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008168	methyltransferase activity
GO:0008270	zinc ion binding
GO:0008327	methyl-CpG binding
GO:0009008	DNA-methyltransferase activity

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006306	DNA methylation
GO:0006351	transcription, DNA-templated
GO:0010216	maintenance of DNA methylation
GO:0010468	regulation of gene expression
GO:0010628	positive regulation of gene expression
GO:0016458	gene silencing
GO:0016568	chromatin modification
GO:0042127	regulation of cell proliferation
GO:0045892	negative regulation of transcription, DNA-templated
GO:0051571	positive regulation of histone H3-K4 methylation
GO:0051573	negative regulation of histone H3-K9 methylation
GO:0071230	cellular response to amino acid stimulus
GO:0090116	C-5 methylation of cytosine

Cellular Component

GO:0000792	heterochromatin
GO:0005634	nucleus
GO:0005657	replication fork
GO:0005721	centromeric heterochromatin
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

MGI:94912

InterPro

IPR001025 Bromo adjacent homology (BAH) domain
IPR001525 C-5 cytosine methyltransferase
IPR002857 Zinc finger, CXXC-type
IPR010506 DMAP1-binding
IPR017198 DNA (cytosine-5)-methyltransferase 1, eukaryote
IPR022702 DNA (cytosine-5)-methyltransferase 1, replication foci domain
IPR029063 S-adenosyl-L-methionine-dependent methyltransferase-like

PFAM

PF01426
PF00145
PF02008
PF06464
PF12047

PRINTS

PR00105

PIRSF

PIRSF037404

SMART

SM00439

TIGRFAMs

Post-translational Modifications

Modification

Cross-References