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MTRR 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [ Homo sapiens (human) ]

Gene ID: 4552, updated on 8-Dec-2018

Summary

Official Symbol
MTRRprovided by HGNC
Official Full Name
5-methyltetrahydrofolate-homocysteine methyltransferase reductaseprovided by HGNC
Primary source
HGNC:HGNC:7473
See related
Ensembl:ENSG00000124275 MIM:602568
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MSR; cblE
Summary
This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]
Expression
Ubiquitous expression in lung (RPKM 14.2), kidney (RPKM 10.4) and 25 other tissues See more
Orthologs

Genomic context

See MTRR in Genome Data Viewer
Location:
5p15.31
Exon count:
21
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (7851186..7901124)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (7851299..7901237)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107986403 Neighboring gene long intergenic non-protein coding RNA 2142 Neighboring gene uncharacterized LOC105374646 Neighboring gene adenylate cyclase 2 Neighboring gene chromosome 5 open reading frame 49 Neighboring gene FAST kinase domains 3 Neighboring gene semaphorin 5A pseudogene Neighboring gene RNA, U1 small nuclear 76, pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Biological oxidations, organism-specific biosystem (from REACTOME)
    Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
  • Cobalamin (Cbl, vitamin B12) transport and metabolism, organism-specific biosystem (from REACTOME)
    Cobalamin (Cbl, vitamin B12) transport and metabolism, organism-specific biosystemVitamin B12 (cobalamin, Cbl) is a water-soluble vitamin with a key role in blood formation and normal functioning of the brain and nervous system. Cbl consists of a planar corrin ring coordinating wi...
  • Defective MTR causes methylmalonic aciduria and homocystinuria type cblG, organism-specific biosystem (from REACTOME)
    Defective MTR causes methylmalonic aciduria and homocystinuria type cblG, organism-specific biosystemDefects in MTR cause methylcobalamin deficiency type G (cblG; MIM:250940), an autosomal recessive inherited disease that causes mental retardation, macrocytic anemia, and homocystinuria (Leclerc et a...
  • Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE, organism-specific biosystem (from REACTOME)
    Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE, organism-specific biosystemDefects in MTRR cause methylcobalamin deficiency type E (cblE; methionine synthase reductase deficiency; MIM:236270) (Wilson et al. 1999). Patients with cblE exhibit megaloblastic anemia and hyperhom...
  • Defects in cobalamin (B12) metabolism, organism-specific biosystem (from REACTOME)
    Defects in cobalamin (B12) metabolism, organism-specific biosystemCobalamin (Cbl, vitamin B12) is a nutrient essential for normal functioning of the brain and nervous system and for the formation of blood. Cbl-dependent methionine synthase (MTR) is required for con...
  • Defects in vitamin and cofactor metabolism, organism-specific biosystem (from REACTOME)
    Defects in vitamin and cofactor metabolism, organism-specific biosystemVitamins are essential nutrients, required in small amounts from the diet for the normal growth and development of a multicellular organism. Where there is vitamin deficiency, either by poor diet or ...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of metabolism, organism-specific biosystem (from REACTOME)
    Diseases of metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Folate Metabolism, organism-specific biosystem (from WikiPathways)
    Folate Metabolism, organism-specific biosystem
    Folate Metabolism
  • Metabolism, organism-specific biosystem (from REACTOME)
    Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
    Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
  • Metabolism of vitamins and cofactors, organism-specific biosystem (from REACTOME)
    Metabolism of vitamins and cofactors, organism-specific biosystemVitamins are a diverse group of organic compounds, classified according to their solubility, either fat-soluble or water-soluble, that are either not synthesized or synthesized only in limited amount...
  • Metabolism of water-soluble vitamins and cofactors, organism-specific biosystem (from REACTOME)
    Metabolism of water-soluble vitamins and cofactors, organism-specific biosystemVitamins are a diverse group of organic compounds, required in small amounts in the diet. They have distinct biochemical roles, often as coenzymes, and are either not synthesized or synthesized only ...
  • Methylation, organism-specific biosystem (from REACTOME)
    Methylation, organism-specific biosystemMethylation is a common but minor pathway of Phase II conjugation compared to glucuronidation or sulfonation. The cofactor used in methylation conjugation is S-adenosylmethionine (SAM). SAM is the ...
  • One Carbon Metabolism, organism-specific biosystem (from WikiPathways)
    One Carbon Metabolism, organism-specific biosystemThis one-carbon metabolism pathway is centered around folate. Folate has two key carbon-carbon double bonds. Saturating one of them yields dihydrofolate (DHF) and adding an additional molecule of hyd...
  • Phase II conjugation, organism-specific biosystem (from REACTOME)
    Phase II conjugation, organism-specific biosystemPhase II of biotransformation is concerned with conjugation, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involv...
  • Sulfur amino acid metabolism, organism-specific biosystem (from REACTOME)
    Sulfur amino acid metabolism, organism-specific biosystemThe main sulfur amino acids are methionine, cysteine, homocysteine and taurine. Of these, the first two are proteinogenic.This group of reactions contains all processes that 1) break down sulfur amin...
  • Vitamin B12 Metabolism, organism-specific biosystem (from WikiPathways)
    Vitamin B12 Metabolism, organism-specific biosystem
    Vitamin B12 Metabolism

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC129643

Gene Ontology Provided by GOA

Function Evidence Code Pubs
FAD binding IDA
Inferred from Direct Assay
more info
PubMed 
FMN binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
FMN binding IDA
Inferred from Direct Assay
more info
PubMed 
FMN binding TAS
Traceable Author Statement
more info
PubMed 
NADP binding TAS
Traceable Author Statement
more info
PubMed 
NADPH binding IDA
Inferred from Direct Assay
more info
PubMed 
NADPH-hemoprotein reductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NADPH-hemoprotein reductase activity IDA
Inferred from Direct Assay
more info
PubMed 
[methionine synthase] reductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
[methionine synthase] reductase activity IDA
Inferred from Direct Assay
more info
PubMed 
[methionine synthase] reductase activity TAS
Traceable Author Statement
more info
PubMed 
aquacobalamin reductase (NADPH) activity IDA
Inferred from Direct Assay
more info
PubMed 
flavin adenine dinucleotide binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
flavin adenine dinucleotide binding IDA
Inferred from Direct Assay
more info
PubMed 
flavin adenine dinucleotide binding TAS
Traceable Author Statement
more info
PubMed 
oxidoreductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
DNA methylation ISS
Inferred from Sequence or Structural Similarity
more info
 
S-adenosylmethionine cycle ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cobalamin metabolic process TAS
Traceable Author Statement
more info
 
folic acid metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
folic acid metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
 
homocysteine catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
homocysteine metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
methionine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
methionine biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
methionine metabolic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cystathionine beta-synthase activity IDA
Inferred from Direct Assay
more info
PubMed 
oxidation-reduction process TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
methionine synthase reductase
Names
[methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing)
methionine synthase reductase, mitochondrial
NP_002445.2
XP_024301831.1
XP_024301832.1
XP_024301833.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008856.1 RefSeqGene

    Range
    5001..37021
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001364440.1NP_001351369.1  methionine synthase reductase

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) represents the longest transcript. Variants 1, 2, 6, 7, and 8 all encode the same protein.
    Source sequence(s)
    AC010346, AC025174
    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin
  2. NM_001364441.1NP_001351370.1  methionine synthase reductase

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
    Source sequence(s)
    AC010346, AC025174
    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin
  3. NM_001364442.1NP_001351371.1  methionine synthase reductase

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
    Source sequence(s)
    AC010346, AC025174
    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin
  4. NM_002454.2NP_002445.2  methionine synthase reductase

    See identical proteins and their annotated locations for NP_002445.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
    Source sequence(s)
    BC054816, BC109216
    Consensus CDS
    CCDS47190.1
    UniProtKB/Swiss-Prot
    Q9UBK8
    Related
    ENSP00000402510.2, ENST00000440940.6
    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin
  5. NM_024010.3NP_076915.3  methionine synthase reductase

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
    Source sequence(s)
    AC010346, AC025174
    Consensus CDS
    CCDS3874.1
    Related
    ENSP00000264668.2, ENST00000264668.6
    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin

RNA

  1. NR_134480.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    BC054816, BC109217, DA384356
  2. NR_134481.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF121214, BC035977, BC054816
  3. NR_134482.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    BC054816, BC062577, BC109217
    Related
    ENST00000511461.5
  4. NR_157168.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  5. NR_157169.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  6. NR_157170.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  7. NR_157171.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  8. NR_157172.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  9. NR_157173.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  10. NR_157174.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  11. NR_157175.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  12. NR_157176.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  13. NR_157177.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174
  14. NR_157178.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010346, AC025174

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    7851186..7901124
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024446064.1XP_024301832.1  methionine synthase reductase isoform X2

    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin
  2. XM_024446065.1XP_024301833.1  methionine synthase reductase isoform X2

    Conserved Domains (2) summary
    cd06203
    Location:277697
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:6142
    Flavodoxin_1; Flavodoxin
  3. XM_024446063.1XP_024301831.1  methionine synthase reductase isoform X1

    Conserved Domains (2) summary
    cd06203
    Location:292712
    methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
    pfam00258
    Location:21157
    Flavodoxin_1

RNA

  1. XR_001742077.1 RNA Sequence

  2. XR_001742076.1 RNA Sequence

  3. XR_001742071.1 RNA Sequence

  4. XR_925614.1 RNA Sequence

  5. XR_001742072.1 RNA Sequence

  6. XR_001742075.1 RNA Sequence

  7. XR_001742074.1 RNA Sequence

    Related
    ENST00000510525.5
  8. XR_001742070.2 RNA Sequence

  9. XR_001742073.2 RNA Sequence

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