MBD2: Methyl-CpG Binding Domain Protein 2
A key reader of DNA methylation involved in gene silencing, development, and cancer
Gene Information Card
| Symbol | MBD2 |
|---|---|
| Full Name | Methyl-CpG Binding Domain Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.2 |
| NCBI Gene ID | 8932 ncbi.nlm.nih.gov/gene/8932 |
| Ensembl ID | ENSG00000134046 |
| UniProt ID | Q9UBB5 |
| OMIM ID | 603547 |
| HGNC ID | 6916 |
| Aliases | DMTase, NY-CO-41, MBD2b, MBD2a |
Description
MBD2 (Methyl-CpG Binding Domain Protein 2) encodes a member of the methyl-CpG-binding domain (MBD) family. The protein binds specifically to methylated DNA and recruits histone deacetylase and chromatin remodeling complexes to silence gene expression. MBD2 is also reported to possess DNA demethylase activity, though this remains controversial. It plays roles in development, genomic imprinting, and tumor suppression. Alternative splicing generates two isoforms: MBD2a and MBD2b.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | MBD2 overexpression correlates with hypermethylation of tumor suppressor gene promoters, contributing to gene silencing and tumor progression. | PMID: 15601830; COSMIC |
| Breast Cancer | MBD2 is upregulated in breast tumors and promotes metastasis by repressing pro-apoptotic genes. | PMID: 19258506; COSMIC |
| Prostate Cancer | MBD2 expression is elevated and associated with poor prognosis; it mediates silencing of GSTP1 and other tumor suppressors. | PMID: 16982746; COSMIC |
| Lung Cancer | MBD2 is overexpressed in non-small cell lung cancer and linked to aberrant DNA methylation patterns. | PMID: 19706757; COSMIC |
| Rett Syndrome (atypical) | Mutations in MBD2 have been reported in patients with Rett-like phenotypes, though MECP2 is the primary gene. | ClinVar; PMID: 20613863 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Lung | 6.5 | Medium |
| Colon | 5.1 | Low |
| Breast | 4.8 | Low |
| Prostate | 4.3 | Low |
| Testis | 3.9 | Low |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 7.8 | Cervical cancer cell line |
| MCF7 | 6.2 | Breast cancer cell line |
| A549 | 5.9 | Lung cancer cell line |
| HCT116 | 5.5 | Colorectal cancer cell line |
| PC3 | 4.1 | Prostate cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.286C>T (p.Arg96Trp) | Missense | <0.1% | Disrupts methyl-CpG binding domain; reduced DNA binding |
| c.421G>A (p.Glu141Lys) | Missense | <0.1% | Unknown significance |
| c.1030C>T (p.Arg344*) | Nonsense | <0.1% | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg344*) lead to truncated protein lacking the C-terminal domain required for transcriptional repression.
Gain of Function (GOF)
Not well documented; overexpression in cancers may act as a gain-of-function by enhancing silencing of tumor suppressors.
Dominant Negative (DN)
Mutations in the methyl-CpG binding domain (e.g., p.Arg96Trp) may produce a protein that binds DNA but fails to recruit repressor complexes, interfering with wild-type MBD2 function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003677 - DNA binding | • GO:0008327 - methyl-CpG binding |
| • GO:0005515 - protein binding | • GO:0005634 - nucleus |
| • GO:0006355 - regulation of transcription | • DNA-templated |
| • GO:0000122 - negative regulation of transcription by RNA polymerase II | • GO:0006306 - DNA methylation-dependent heterochromatin formation |
| • GO:0035511 - oxidative DNA demethylase activity |
Pathways
• DNA methylation and transcriptional repression (Reactome: R-HSA-212300)
• Chromatin modifying enzymes (Reactome: R-HSA-3244102)
• Epigenetic regulation of gene expression (KEGG: hsa05200)
Protein Summary
MBD2 is a 411-amino acid protein (isoform MBD2a) containing an N-terminal methyl-CpG binding domain (MBD) and a C-terminal transcriptional repression domain (TRD). It binds symmetrically methylated CpG dinucleotides and recruits the NuRD (nucleosome remodeling and deacetylase) complex to silence gene expression. MBD2 is also implicated in active DNA demethylation via its putative demethylase activity. The protein is widely expressed, with highest levels in brain and lung. Overexpression in multiple cancers suggests an oncogenic role through epigenetic silencing of tumor suppressor genes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MBD2 Knockout HEK293 Cell Line | EDJ-KQ2162 | Human | 8932 | Details Get a Quote |
| MBD2 Knockout A-549 Cell Line | EDJ-KQ22361 | Human | 8932 | Details Get a Quote |
| MBD2 Knockout HCT 116 Cell Line | EDJ-KQ22362 | Human | 8932 | Details Get a Quote |
| MBD2 Knockout HeLa Cell Line | EDJ-KQ22363 | Human | 8932 | Details Get a Quote |
| MBD2 Knockout T-47D-CAS9 Cell Line | EDC08338 | Human | 8932 | Details Get a Quote |
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