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MTRR/MSR

OverviewProducts

Function

Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species (Probable). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme (PubMed:16769880). Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (PubMed:16769880).

Involvement in disease

Homocystinuria-megaloblastic anemia, cblE complementation type

HMAE

An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent.

None

The disease is caused by variants affecting the gene represented in this entry.

Neural tube defects, folate-sensitive

NTDFS

The most common NTDs are open spina bifida (myelomeningocele) and anencephaly.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Tissue specificity

Found in all tissues tested, particularly abundant in skeletal muscle.

Cellular localization

  • Isoform B
  • Cytoplasm
  • Isoform A
  • Cytoplasm

Alternative names

  • Methionine synthase reductase
  • MSR
  • Aquacobalamin reductase
  • AqCbl reductase
  • MTRR

Database links

Target type

Proteins

Molecular weight

77674Da