Entry - *156360 - METALLOTHIONEIN 2A; MT2A - OMIM
 
* 156360

METALLOTHIONEIN 2A; MT2A


Alternative titles; symbols

METALLOTHIONEIN II; MT2


Other entities represented in this entry:

METALLOTHIONEIN II PROCESSED PSEUDOGENE, INCLUDED; MT2P1, INCLUDED

HGNC Approved Gene Symbol: MT2A

Cytogenetic location: 16q13     Genomic coordinates (GRCh38): 16:56,608,584-56,609,497 (from NCBI)


TEXT

Cloning and Expression

For background information on metallothioneins, see 156350. Karin and Richards (1982) cloned a human MT-II gene and determined the sequence of the mRNA. It showed a GC-rich sequence; 79% of codons had G or C residues at the third position.


Mapping

Bates and Mulley (1988) identified a BamHI RFLP at the MT2A locus. This locus was assigned to 16q21 by in situ hybridization to chromosomes expressing FRA16B and FRA16C, 2 fragile sites on chromosome 16 (Simmers et al., 1987).

Pseudogenes

A polymorphic processed pseudogene of metallothionein II, called MT2P, is located on chromosome 4p11-4q21 (Schmidt et al., 1984; Lieberman et al., 1985), according to molecular studies in somatic cell hybrids and in situ hybridization. Pakstis et al. (1986) demonstrated that MTP1 is separated from GC (139200) by only 5% recombination; thus, it is probably on 4q.


Gene Function

Concentrations of acetyl-coenzyme A and NAD+ affect histone acetylation and thereby couple cellular metabolic status and transcriptional regulation. Shimazu et al. (2013) reported that the ketone body D-beta-hydroxybutyrate (beta-OHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous beta-OHB, or fasting or calorie restriction, 2 conditions associated with increased beta-OHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by beta-OHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors Foxo3a (602681) and Mt2. Treatment of cells with beta-OHB increased histone acetylation at the Foxo3a and Mt2 promoters, and both genes were activated by selective depletion of Hdac1 (601241) and Hdac2 (605164). Consistent with increased Foxo3a and Mt2 activity, treatment of mice with beta-OHB conferred substantial protection against oxidative stress.


REFERENCES

  1. Bates, L. J., Mulley, J. C. A BamHI RFLP at MT2A on human chromosome 16. Nucleic Acids Res. 16: 9071 only, 1988. [PubMed: 2902572, related citations] [Full Text]

  2. Karin, M., Richards, R. I. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene. Nature 299: 797-802, 1982. [PubMed: 7133118, related citations] [Full Text]

  3. Lieberman, H. B., Rabin, M., Barker, P. E., Ruddle, F. H., Varshney, U., Gedamu, L. Human metallothionein-II processed gene is located in region p11-q21 of chromosome 4. Cytogenet. Cell Genet. 39: 109-115, 1985. [PubMed: 2988861, related citations] [Full Text]

  4. Pakstis, A. J., Kidd, J. R., Castiglione, C., Sparkes, R. S., Kidd, K. K. Close linkage of MT2P1 with GC on chromosome 4. Cytogenet. Cell Genet. 41: 189-190, 1986. [PubMed: 3956270, related citations] [Full Text]

  5. Schmidt, C. J., Hamer, D. H., McBride, O. W. Chromosomal location of human metallothionein genes: implications for Menkes' disease. Science 224: 1104-1106, 1984. [PubMed: 6719135, related citations] [Full Text]

  6. Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., Newgard, C. B., Farese, R. V., Jr., de Cabo, R., Ulrich, S., Akassoglou, K., Verdin, E. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339: 211-214, 2013. [PubMed: 23223453, images, related citations] [Full Text]

  7. Simmers, R. N., Sutherland, G. R., West, A., Richards, R. I. Fragile sites at 16q22 are not at the breakpoint of the chromosomal rearrangement in AMMoL. Science 236: 92-94, 1987. [PubMed: 3470945, related citations] [Full Text]


Ada Hamosh - updated : 1/29/2013
Victor A. McKusick - edited : 2/26/1997
Creation Date:
Victor A. McKusick : 6/2/1986
carol : 06/19/2015
alopez : 1/31/2013
terry : 1/29/2013
mark : 2/26/1997
terry : 2/26/1997
supermim : 3/16/1992
carol : 2/18/1992
supermim : 3/20/1990
carol : 2/5/1990
ddp : 10/27/1989
root : 11/2/1988

* 156360

METALLOTHIONEIN 2A; MT2A


Alternative titles; symbols

METALLOTHIONEIN II; MT2


Other entities represented in this entry:

METALLOTHIONEIN II PROCESSED PSEUDOGENE, INCLUDED; MT2P1, INCLUDED

HGNC Approved Gene Symbol: MT2A

Cytogenetic location: 16q13     Genomic coordinates (GRCh38): 16:56,608,584-56,609,497 (from NCBI)


TEXT

Cloning and Expression

For background information on metallothioneins, see 156350. Karin and Richards (1982) cloned a human MT-II gene and determined the sequence of the mRNA. It showed a GC-rich sequence; 79% of codons had G or C residues at the third position.


Mapping

Bates and Mulley (1988) identified a BamHI RFLP at the MT2A locus. This locus was assigned to 16q21 by in situ hybridization to chromosomes expressing FRA16B and FRA16C, 2 fragile sites on chromosome 16 (Simmers et al., 1987).

Pseudogenes

A polymorphic processed pseudogene of metallothionein II, called MT2P, is located on chromosome 4p11-4q21 (Schmidt et al., 1984; Lieberman et al., 1985), according to molecular studies in somatic cell hybrids and in situ hybridization. Pakstis et al. (1986) demonstrated that MTP1 is separated from GC (139200) by only 5% recombination; thus, it is probably on 4q.


Gene Function

Concentrations of acetyl-coenzyme A and NAD+ affect histone acetylation and thereby couple cellular metabolic status and transcriptional regulation. Shimazu et al. (2013) reported that the ketone body D-beta-hydroxybutyrate (beta-OHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous beta-OHB, or fasting or calorie restriction, 2 conditions associated with increased beta-OHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by beta-OHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors Foxo3a (602681) and Mt2. Treatment of cells with beta-OHB increased histone acetylation at the Foxo3a and Mt2 promoters, and both genes were activated by selective depletion of Hdac1 (601241) and Hdac2 (605164). Consistent with increased Foxo3a and Mt2 activity, treatment of mice with beta-OHB conferred substantial protection against oxidative stress.


REFERENCES

  1. Bates, L. J., Mulley, J. C. A BamHI RFLP at MT2A on human chromosome 16. Nucleic Acids Res. 16: 9071 only, 1988. [PubMed: 2902572] [Full Text: https://doi.org/10.1093/nar/16.18.9071]

  2. Karin, M., Richards, R. I. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene. Nature 299: 797-802, 1982. [PubMed: 7133118] [Full Text: https://doi.org/10.1038/299797a0]

  3. Lieberman, H. B., Rabin, M., Barker, P. E., Ruddle, F. H., Varshney, U., Gedamu, L. Human metallothionein-II processed gene is located in region p11-q21 of chromosome 4. Cytogenet. Cell Genet. 39: 109-115, 1985. [PubMed: 2988861] [Full Text: https://doi.org/10.1159/000132117]

  4. Pakstis, A. J., Kidd, J. R., Castiglione, C., Sparkes, R. S., Kidd, K. K. Close linkage of MT2P1 with GC on chromosome 4. Cytogenet. Cell Genet. 41: 189-190, 1986. [PubMed: 3956270] [Full Text: https://doi.org/10.1159/000132226]

  5. Schmidt, C. J., Hamer, D. H., McBride, O. W. Chromosomal location of human metallothionein genes: implications for Menkes' disease. Science 224: 1104-1106, 1984. [PubMed: 6719135] [Full Text: https://doi.org/10.1126/science.6719135]

  6. Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., Newgard, C. B., Farese, R. V., Jr., de Cabo, R., Ulrich, S., Akassoglou, K., Verdin, E. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339: 211-214, 2013. [PubMed: 23223453] [Full Text: https://doi.org/10.1126/science.1227166]

  7. Simmers, R. N., Sutherland, G. R., West, A., Richards, R. I. Fragile sites at 16q22 are not at the breakpoint of the chromosomal rearrangement in AMMoL. Science 236: 92-94, 1987. [PubMed: 3470945] [Full Text: https://doi.org/10.1126/science.3470945]


Contributors:
Ada Hamosh - updated : 1/29/2013
Victor A. McKusick - edited : 2/26/1997

Creation Date:
Victor A. McKusick : 6/2/1986

Edit History:
carol : 06/19/2015
alopez : 1/31/2013
terry : 1/29/2013
mark : 2/26/1997
terry : 2/26/1997
supermim : 3/16/1992
carol : 2/18/1992
supermim : 3/20/1990
carol : 2/5/1990
ddp : 10/27/1989
root : 11/2/1988