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

    Gene ID: 4548, updated on 6-Jun-2024

    Summary

    Official Symbol
    MTRprovided by HGNC
    Official Full Name
    5-methyltetrahydrofolate-homocysteine methyltransferaseprovided by HGNC
    Primary source
    HGNC:HGNC:7468
    See related
    Ensembl:ENSG00000116984 MIM:156570; AllianceGenome:HGNC:7468
    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]
    Expression
    Ubiquitous expression in kidney (RPKM 5.8), thyroid (RPKM 4.9) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See MTR in Genome Data Viewer
    Location:
    1q43
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (236795281..236903981)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (236206330..236315021)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (236958581..237067281)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak785 silencer Neighboring gene galectin 8 Neighboring gene HEAT repeat containing 1 Neighboring gene MPRA-validated peak786 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2825 Neighboring gene MPRA-validated peak787 silencer Neighboring gene control region 3 heart enhancer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2005 Neighboring gene VISTA enhancer hs2135 Neighboring gene actinin alpha 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2826 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2827 Neighboring gene Sharpr-MPRA regulatory region 3741 Neighboring gene ribosomal protein SA pseudogene 21 Neighboring gene uncharacterized LOC105373218 Neighboring gene uncharacterized LOC124904563 Neighboring gene uncharacterized LOC124904564

    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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Methylcobalamin deficiency type cblG Compare labs
    Neural tube defects, folate-sensitive
    MedGen: C1866558 OMIM: 601634 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif interacts with MTR; interaction predicted to be relevant to purine pyrimidine biosynthesis PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ33168, FLJ43216, FLJ45386

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cobalamin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables methionine synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables methionine synthase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables methionine synthase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in axon regeneration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to nitric oxide ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cobalamin metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in homocysteine metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in methionine biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in methionine biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in methylation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in nervous system development TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in response to axon injury ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in tetrahydrofolate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     

    General protein information

    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
    NP_001397871.1
    XP_005273198.1
    XP_011542496.1
    XP_016856818.1
    XP_016856819.1
    XP_047277138.1
    XP_047277139.1
    XP_047277141.1
    XP_047277142.1
    XP_047277143.1
    XP_054192683.1
    XP_054192684.1
    XP_054192685.1
    XP_054192686.1
    XP_054192687.1
    XP_054192688.1
    XP_054192689.1
    XP_054192690.1
    XP_054192691.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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
      5012..113701
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000254.3NP_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)
      AL359185, AL359259
      Consensus CDS
      CCDS1614.1
      UniProtKB/Swiss-Prot
      A1L4N8, A9Z1W4, B7ZLW7, B9EGF7, Q99707, Q99713, Q99723
      UniProtKB/TrEMBL
      B7ZLW8
      Related
      ENSP00000355536.5, ENST00000366577.10
      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:9651246
      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/TrEMBL
      B7ZLW8
      Related
      ENSP00000441845.1, ENST00000535889.6
      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:9141195
      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_001291940.2NP_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/TrEMBL
      B1ANE3
      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:558839
      Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    4. NM_001410942.1NP_001397871.1  methionine synthase isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL359185, AL359259
      Consensus CDS
      CCDS91175.1
      UniProtKB/TrEMBL
      A0A7P0TAJ0, B7ZLW8
      Related
      ENSP00000506109.1, ENST00000679842.1

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      236795281..236903981
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047421186.1XP_047277142.1  methionine synthase isoform X8

      UniProtKB/TrEMBL
      B7ZLW8
    2. XM_005273141.6XP_005273198.1  methionine synthase isoform X3

      UniProtKB/TrEMBL
      B7ZLW8
      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:9641245
      Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    3. XM_047421185.1XP_047277141.1  methionine synthase isoform X7

      UniProtKB/TrEMBL
      B7ZLW8
    4. XM_047421182.1XP_047277138.1  methionine synthase isoform X5

      UniProtKB/TrEMBL
      B7ZLW8
    5. XM_011544194.4XP_011542496.1  methionine synthase isoform X1

      UniProtKB/TrEMBL
      A0A6Q8PGK3
      Related
      ENSP00000502299.2, ENST00000674797.2
      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:10211302
      Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    6. XM_017001330.3XP_016856819.1  methionine synthase isoform X4

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    7. XM_017001329.3XP_016856818.1  methionine synthase isoform X2

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    8. XM_047421183.1XP_047277139.1  methionine synthase isoform X6

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    9. XM_047421187.1XP_047277143.1  methionine synthase isoform X9

      UniProtKB/TrEMBL
      B1ANE3
      Related
      ENSP00000355535.3, ENST00000366576.3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      236206330..236315021
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054336715.1XP_054192690.1  methionine synthase isoform X8

      UniProtKB/TrEMBL
      B7ZLW8
    2. XM_054336710.1XP_054192685.1  methionine synthase isoform X3

      UniProtKB/TrEMBL
      B7ZLW8
    3. XM_054336714.1XP_054192689.1  methionine synthase isoform X7

      UniProtKB/TrEMBL
      B7ZLW8
    4. XM_054336712.1XP_054192687.1  methionine synthase isoform X5

      UniProtKB/TrEMBL
      B7ZLW8
    5. XM_054336708.1XP_054192683.1  methionine synthase isoform X1

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    6. XM_054336711.1XP_054192686.1  methionine synthase isoform X4

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    7. XM_054336709.1XP_054192684.1  methionine synthase isoform X2

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    8. XM_054336713.1XP_054192688.1  methionine synthase isoform X6

      UniProtKB/TrEMBL
      A0A6Q8PGK3
    9. XM_054336716.1XP_054192691.1  methionine synthase isoform X9

      UniProtKB/TrEMBL
      B1ANE3