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

Gene ID: 4548, updated on 26-Jul-2015
Official Symbol
MTRprovided by HGNC
Official Full Name
5-methyltetrahydrofolate-homocysteine methyltransferaseprovided by HGNC
Primary source
HGNC:HGNC:7468
See related
Ensembl:ENSG00000116984; HPRD:01136; MIM:156570; Vega:OTTHUMG00000040060
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
MS; HMAG; cblG
Summary
This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
Orthologs
Location:
1q43
Exon count:
34
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 1 NC_000001.11 (236794304..236903981)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (236958581..237067281)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene lectin, galactoside-binding, soluble, 8 Neighboring gene HEAT repeat containing 1 Neighboring gene actinin, alpha 2 Neighboring gene ribosomal protein SA pseudogene 21 Neighboring gene uncharacterized LOC105373218 Neighboring gene ribosomal protein L35 pseudogene 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
NHGRI GWA Catalog
  • 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 ...
  • Biosynthesis of amino acids, organism-specific biosystem (from KEGG)
    Biosynthesis of amino acids, organism-specific biosystemThis map presents a modular architecture of the biosynthesis pathways of twenty amino acids, which may be viewed as consisting of the core part and its extensions. The core part is the KEGG module fo...
  • Biosynthesis of amino acids, conserved biosystem (from KEGG)
    Biosynthesis of amino acids, conserved biosystemThis map presents a modular architecture of the biosynthesis pathways of twenty amino acids, which may be viewed as consisting of the core part and its extensions. The core part is the KEGG module fo...
  • 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...
  • Cysteine and methionine metabolism, organism-specific biosystem (from KEGG)
    Cysteine and methionine metabolism, organism-specific biosystemCysteine and methionine are sulfur-containing amino acids. Cysteine is synthesized from serine through different pathways in different organism groups. In bacteria and plants, cysteine is converted f...
  • Cysteine and methionine metabolism, conserved biosystem (from KEGG)
    Cysteine and methionine metabolism, conserved biosystemCysteine and methionine are sulfur-containing amino acids. Cysteine is synthesized from serine through different pathways in different organism groups. In bacteria and plants, cysteine is converted f...
  • 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...
  • L-methionine salvage from L-homocysteine, conserved biosystem (from BIOCYC)
    L-methionine salvage from L-homocysteine, conserved biosystemGeneral Background |FRAME: MET "Methionine"| is an essential amino acid in mammals. It is not biosynthesized and must be obtained in the diet. Methionine, or its metabolites, participate in fundamen...
  • Metabolic pathways, organism-specific biosystem (from KEGG)
    Metabolic pathways, organism-specific biosystem
    Metabolic pathways
  • 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, required in small amounts in the diet. They have distinct biochemical roles, often as coenzymes, and are either not synthesized or synthesized only ...
  • 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...
  • One carbon pool by folate, organism-specific biosystem (from KEGG)
    One carbon pool by folate, organism-specific biosystem
    One carbon pool by folate
  • One carbon pool by folate, conserved biosystem (from KEGG)
    One carbon pool by folate, conserved biosystem
    One carbon pool by folate
  • 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...
  • Selenium Pathway, organism-specific biosystem (from WikiPathways)
    Selenium Pathway, organism-specific biosystem
    Selenium Pathway
  • Selenocompound metabolism, organism-specific biosystem (from KEGG)
    Selenocompound metabolism, organism-specific biosystem
    Selenocompound metabolism
  • Selenocompound metabolism, conserved biosystem (from KEGG)
    Selenocompound metabolism, conserved biosystem
    Selenocompound metabolism
  • 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...
  • Trans-sulfuration and one carbon metabolism, organism-specific biosystem (from WikiPathways)
    Trans-sulfuration and one carbon metabolism, organism-specific biosystem
    Trans-sulfuration and one carbon metabolism
  • Trans-sulfuration pathway, organism-specific biosystem (from WikiPathways)
    Trans-sulfuration pathway, organism-specific biosystemTrans-sulfuration pathway, the pathway of production of GSH from S-adenosylmethionine (SAMe). Evidences have been showed that this pathway was perturbed in liver toxicity studies.
  • folate transformations I, organism-specific biosystem (from BIOCYC)
    folate transformations I, organism-specific biosystemBackground The various folate coenzymes are essential cofactors that facilitate the transfer of one-carbon units from donor molecules into important biosynthetic pathways leading to methionine, puri...
  • methionine salvage, organism-specific biosystem (from BIOCYC)
    methionine salvage, organism-specific biosystemGeneral Background : MET "Methionine" is an essential amino acid in mammals. It is not biosynthesized and must be obtained in the diet. Methionine, or its metabolites, participate in fundamental pro...
  • superpathway of L-methionine salvage and degradation, conserved biosystem (from BIOCYC)
    superpathway of L-methionine salvage and degradation, conserved biosystemPlease note: This is a superpathway that describes the degradation of the amino acid |FRAME: MET| in mammals. For more information about this pathway, please consult the different subpathways that ma...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ33168, FLJ43216, FLJ45386

Gene Ontology Provided by GOA

Function Evidence Code Pubs
S-adenosylmethionine-homocysteine S-methyltransferase activity IEA
Inferred from Electronic Annotation
more info
 
cobalamin binding IEA
Inferred from Electronic Annotation
more info
 
methionine synthase activity IDA
Inferred from Direct Assay
more info
PubMed 
methionine synthase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
zinc ion binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
axon regeneration ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular nitrogen compound metabolic process TAS
Traceable Author Statement
more info
 
cellular response to nitric oxide ISS
Inferred from Sequence or Structural Similarity
more info
 
cobalamin metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
cobalamin metabolic process TAS
Traceable Author Statement
more info
 
methionine biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
methylation TAS
Traceable Author Statement
more info
 
nervous system development TAS
Traceable Author Statement
more info
PubMed 
pteridine-containing compound metabolic process IEA
Inferred from Electronic Annotation
more info
 
response to axon injury ISS
Inferred from Sequence or Structural Similarity
more info
 
small molecule metabolic process TAS
Traceable Author Statement
more info
 
sulfur amino acid metabolic process TAS
Traceable Author Statement
more info
 
vitamin metabolic process TAS
Traceable Author Statement
more info
 
water-soluble vitamin metabolic process TAS
Traceable Author Statement
more info
 
xenobiotic metabolic process TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
Preferred Names
methionine synthase
Names
5-methyltetrahydrofolate-homocysteine methyltransferase 1
cobalamin-dependent methionine synthase
vitamin-B12 dependent methionine synthase
NP_000245.2
NP_001278868.1
NP_001278869.1

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_008959.1 RefSeqGene

    Range
    5001..113701
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000254.2NP_000245.2  methionine synthase isoform 1

    See identical proteins and their annotated locations for NP_000245.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL359259, DC377743, U73338, U75743
    Consensus CDS
    CCDS1614.1
    UniProtKB/Swiss-Prot
    Q99707
    Related
    ENSP00000355536, OTTHUMP00000037964, ENST00000366577, OTTHUMT00000096632
    Conserved Domains (5) summary
    COG0646
    Location:21340
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:191261
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:371627
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:671897
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:9641247
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
  2. NM_001291939.1NP_001278868.1  methionine synthase isoform 2

    See identical proteins and their annotated locations for NP_001278868.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
    Source sequence(s)
    AL359259, BC144095, CB241165, DC377743
    Consensus CDS
    CCDS73054.1
    UniProtKB/Swiss-Prot
    Q99707
    Related
    ENSP00000441845, ENST00000535889
    Conserved Domains (5) summary
    COG0646
    Location:21340
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:191210
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:371627
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    pfam02965
    Location:9131196
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    cl00293
    Location:679846
    B12-binding_like; B12 binding domain (B12-BD). Most of the members bind different cobalamid derivates, like B12 (adenosylcobamide) or methylcobalamin or methyl-Co(III) 5-hydroxybenzimidazolylcobamide. This domain is found in several enzymes, such as glutamate mutase, ...
  3. NM_001291940.1NP_001278869.1  methionine synthase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an internal exon, which causes translation initiation at a downstream AUG, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AL359259, BC136440, BC144098, CB241165, DC377743
    UniProtKB/Swiss-Prot
    Q99707
    Conserved Domains (4) summary
    COG1410
    Location:2823
    MetH2; Methionine synthase I, cobalamin-binding domain [Amino acid transport and metabolism]
    cd00740
    Location:1220
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:264490
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:557840
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p2 Primary Assembly

    Range
    236794304..236903981
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011544193.1XP_011542495.1  

    Conserved Domains (5) summary
    COG0646
    Location:21340
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:191198
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:371627
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    pfam02965
    Location:9011184
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    cl00293
    Location:671834
    B12-binding_like; B12 binding domain (B12-BD). Most of the members bind different cobalamid derivates, like B12 (adenosylcobamide) or methylcobalamin or methyl-Co(III) 5-hydroxybenzimidazolylcobamide. This domain is found in several enzymes, such as glutamate mutase, ...
  2. XM_005273141.3XP_005273198.1  

    Conserved Domains (5) summary
    COG0646
    Location:20339
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:181260
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:370626
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:670896
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:9631246
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
  3. XM_011544194.1XP_011542496.1  

    Conserved Domains (5) summary
    COG0646
    Location:140396
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:1401317
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:427683
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:727953
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:10201303
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
  4. XM_006711769.2XP_006711832.1  

    Conserved Domains (5) summary
    COG0646
    Location:21340
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    cd00740
    Location:371627
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:671897
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:9641135
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    TIGR02082
    Location:261136
    metH; 5-methyltetrahydrofolate--homocysteine methyltransferase
  5. XM_006711770.1XP_006711833.1  

    Conserved Domains (5) summary
    COG1410
    Location:30918
    MetH2; Methionine synthase I, cobalamin-binding domain [Amino acid transport and metabolism]
    cd00740
    Location:59315
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:359585
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:652935
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    cl22882
    Location:228
    S-methyl_trans; Homocysteine S-methyltransferase

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 Alternate CHM1_1.1

    Range
    238230032..238338720
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)