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

Gene ID: 4548, updated on 10-Jan-2019

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
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

Genomic context

See MTR in Genome Data Viewer
Location:
1q43
Exon count:
33
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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 control region 3 heart enhancer Neighboring gene VISTA enhancer hs2135 Neighboring gene actinin alpha 2 Neighboring gene ribosomal protein SA pseudogene 21 Neighboring gene uncharacterized LOC105373218 Neighboring gene uncharacterized LOC107985368 Neighboring gene ribosomal protein L35 pseudogene 1

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 FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
NHGRI GWA 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 BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ33168, FLJ43216, FLJ45386

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cobalamin binding IEA
Inferred from Electronic Annotation
more info
 
methionine synthase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 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 IEA
Inferred from Electronic Annotation
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
 
Component Evidence Code Pubs
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
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
XP_005273198.1
XP_006711833.1
XP_011542496.1
XP_016856818.1
XP_016856819.1

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_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
    ENSP00000355536.5, ENST00000366577.9
    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/Swiss-Prot
    Q99707
    Related
    ENSP00000441845.1, ENST00000535889.5
    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_001291940.1NP_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
    Related
    ENSP00000355535.3, ENST00000366576.3
    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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 Primary Assembly

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

mRNA and Protein(s)

  1. XM_011544194.3XP_011542496.1  methionine synthase isoform X1

    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
  2. XM_017001330.2XP_016856819.1  methionine synthase isoform X4

  3. XM_017001329.2XP_016856818.1  methionine synthase isoform X2

  4. XM_005273141.5XP_005273198.1  methionine synthase isoform X3

    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
  5. XM_006711770.3XP_006711833.1  methionine synthase isoform X5

    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:653934
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    cl22882
    Location:228
    S-methyl_trans; Homocysteine S-methyltransferase
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