MTRR - Methionine synthase reductase - human protein (Function)
 
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MTRR »  Methionine synthase reductase   [ EC 1.16.1.8 ]  (MSR)
 
Gene name:  MTRR
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups from the folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining the transgenerational epigenetic inheritance effects.  
2
  • UniProtKB
GO molecular function 
[methionine synthase] reductase activitydefinition[GO:0030586]  
3
  • UniProtKB
  • BHF-UCL
Aquacobalamin reductase (NADPH) activitydefinition[GO:0050444] silver  
1
  • CACAO
FAD bindingdefinition[GO:0071949]  
1
  • BHF-UCL
Flavin adenine dinucleotide bindingdefinition[GO:0050660]  
2
  • UniProtKB
FMN bindingdefinition[GO:0010181]  
2
  • BHF-UCL
  • UniProtKB
Iron ion bindingdefinition[GO:0005506] silver  
1
  • InterPro 2 GO
NADP bindingdefinition[GO:0050661]  
1
  • UniProtKB
NADPH bindingdefinition[GO:0070402]  
1
  • BHF-UCL
Contradiction  NADPH-hemoprotein reductase activitydefinition[GO:0003958]  
2
  • BHF-UCL
  • RefGenome
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygendefinition[GO:0016709]  
1
  • RefGenome
Oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptordefinition[GO:0016723]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IntAct
GO biological process 
DNA methylationdefinition[GO:0006306]  
1
  • Ortholog Curator
Folic acid metabolic processdefinition[GO:0046655]  
2
  • BHF-UCL
  • Ortholog Curator
Homocysteine catabolic processdefinition[GO:0043418]  
1
  • BHF-UCL
Methionine biosynthetic processdefinition[GO:0009086]  
1
  • BHF-UCL
Methionine metabolic processdefinition[GO:0006555]  
1
  • UniProtKB
Negative regulation of cystathionine beta-synthase activitydefinition[GO:1904042]  
1
  • BHF-UCL
Oxidation-reduction processdefinition[GO:0055114]  
1
  • UniProtKB
S-adenosylmethionine cycledefinition[GO:0033353]  
1
  • BHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 1.16.1.8: 2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP(+) 2 [methionine synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine.  
2
  • UniProtKB
It requires the following cofactors
 FAD  
2
  • UniProtKB
 FMN  
2
  • UniProtKB
 
More information is available from:
Pathways 
According to Reactome, this protein belongs to the following pathways:
Cobalamin (Cbl, vitamin B12) transport and metabolism  REACT_163862  
Defective MTR causes methylmalonic aciduria and homocystinuria type cblG  REACT_169149  
Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE  REACT_169439  
Methylation  REACT_6946  
Sulfur amino acid metabolism  REACT_115639  
 
More information is available from:
 

Biophysicochemical properties

Kinetic parameters
KM 3540 uM for NADH
KM 2.89 uM for NADPH

Keywords

Biological process 
Amino-acid biosynthesis  definition   [KW-0028]
Methionine biosynthesis  definition   [KW-0486]
Molecular function 
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: Q9UBK8
Other
GeneWiki: MTRR_(gene)
GenomeRNAi: 4552
PRO: PR:Q9UBK8