MBD2 (NM_003927.3) is a gene of 70,583 bp coded by 7 exons from 33,240,260 to 33,169,677 according to NCBI reference sequence NT_010966.14 or 51,751,158 to 51,680,575 according to Genome reference consortium human build 37 GRCh37. There is an alternative transcript for MBD2 (NM_015832.3) of 22,111 bp from 33,240,260 to 33,218,149 on NCBI reference sequence NT_010966.14. This transcript shares the first 2 exons (coding for the methyl binding domain) but differs in the 3rd exon, resulting in a shorter truncated protein.

The longer transcript encoded by NM_003927.3, mRNA length of 2584bp, is expressed ubiquitiously (according to symatlas).
The shorter transcript NM_015832.3, mRNA length of 1357bp is expressed in germ cells (according to symatlas).

In somatic tissues MBD2 is expressed from a single transcript, and is detected by western blot as 2 stable proteins at approximately 50 kDa (MBD2a) and 30 kDa (MBD2b). Human MBD2a (Q9UBB5) has 411 amino acids. It is unknown whether MBD2b is due to use of an alternative translation start site (creating protein of 262 amino acids) or due to protein cleavage/processing/degradation.
Human germ cells express a short form of MBD2 from the alternative transcript with an expected length of 302 amino acids.

MBD2a and MBD2b are expressed in all tissues tested with highest levels in spleen and colon nuclei (non-published observation).

MBD2 is a nuclear protein. MBD2-GFP localises to major satellite in mouse ES cells, but not in DNA methylation deficient cells (Hendrich and Bird, 1998).

MBD2 is a methyl binding protein that is thought to repress gene expression as part of the NuRD complex. The NuRD complex was identified independently by four separate groups (Wade et al., 1998; Tong et al., 1998; Xue et al., 1998; Zhang et al., 1998). NuRD consists of a chromatin remodelling ATPase Mi2alpha or beta, histone deacetylase HDAC1/HDAC2, MTA1 or MTA2, RbAp46/RbAp48, p66alpha/beta and can also contain MBD2 or MBD3. TAP tagged MBD2a associates with NuRD with equimolar stoichometry implying that most MBD2a is complexed with NuRD in cells (Le Guezennec et al., 2006). MBD2 is required for repression of methylated reporter genes (Hendrich, 2001) and many endogenous target genes of MBD2 have been reported. However the global genomic targets of MBD2 have not been characterised. MBD2 knock out are viable and fertile, and show only mild physiological defects. These are abnormal maternal behaviour and T helper cell deficiencies (Hendrich, 2001; Hutchins, 2002; Hutchins, 2005).

MBD2 is a member of the methyl-binding domain proteins (Hendrich and Bird, 1998). Other members of this family are MeCp2, MBD2, MBD3 and MBD4 (Klose and Bird, 2006). These proteins share a region of homology (145-213 of MBD2a), which have been shown to form a stable domain consisting of a beta sheet, an alpha helix and a positioned loop (Ohki et al., 2001). The crystal structure of the MBD of MeCP2 complexed with a methylated CpG containing 20mer of DNA indicates that the protein-DNA interactions are dependent on water molecules (Ho et al., 2008). The protein with closest homology to MBD2 is MBD3, however MBD3 has two crucial amino acid substitutions in the MBD and does not specifically bind to methylated DNA (Hendrich and Tweedie, 2003).

MBD2 is mutated only infrequently in human cancer tissues.