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Aliases for MTR Gene

Aliases for MTR Gene

  • 5-Methyltetrahydrofolate-Homocysteine Methyltransferase 2 3 5
  • Vitamin-B12 Dependent Methionine Synthase 3 4
  • EC 2.1.1.13 4 63
  • MS 3 4
  • 5-Methyltetrahydrofolate-Homocysteine Methyltransferase 1 3
  • 5-Methyltetrahydrofolate--Homocysteine Methyltransferase 4
  • Cobalamin-Dependent Methionine Synthase 3
  • HMAG 3
  • CblG 3

External Ids for MTR Gene

Previous GeneCards Identifiers for MTR Gene

  • GC01P235091
  • GC01P232412
  • GC01P233255
  • GC01P233999
  • GC01P233284
  • GC01P235025
  • GC01P236958
  • GC01P207414

Summaries for MTR Gene

Entrez Gene Summary for MTR Gene

  • 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]

GeneCards Summary for MTR Gene

MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase) is a Protein Coding gene. Diseases associated with MTR include homocystinuria-megaloblastic anemia, cblg complementation type and neural tube defects, folate-sensitive. Among its related pathways are Metabolism and Infectious disease. GO annotations related to this gene include cobalamin binding and methionine synthase activity.

UniProtKB/Swiss-Prot for MTR Gene

  • Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

Gene Wiki entry for MTR Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MTR Gene

Genomics for MTR Gene

Regulatory Elements for MTR Gene

Promoters for MTR Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around MTR on UCSC Golden Path with GeneCards custom track

Genomic Location for MTR Gene

Chromosome:
1
Start:
236,794,304 bp from pter
End:
236,903,981 bp from pter
Size:
109,678 bases
Orientation:
Plus strand

Genomic View for MTR Gene

Genes around MTR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MTR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MTR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTR Gene

Proteins for MTR Gene

  • Protein details for MTR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99707-METH_HUMAN
    Recommended name:
    Methionine synthase
    Protein Accession:
    Q99707
    Secondary Accessions:
    • A1L4N8
    • A9Z1W4
    • B7ZLW7
    • B9EGF7
    • Q99713
    • Q99723

    Protein attributes for MTR Gene

    Size:
    1265 amino acids
    Molecular mass:
    140527 Da
    Cofactor:
    Name=methyl(III)cobalamin; Xref=ChEBI:CHEBI:28115;
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • L-homocysteine is bound via the zinc atom.

    Three dimensional structures from OCA and Proteopedia for MTR Gene

    Alternative splice isoforms for MTR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MTR Gene

Proteomics data for MTR Gene at MOPED

Post-translational modifications for MTR Gene

  • Ubiquitination at Lys 16, Lys 28, Lys 127, Lys 151, Lys 216, Lys 231, Lys 685, Lys 727, Lys 735, Lys 753, Lys 781, Lys 789, Lys 814, Lys 817, Lys 823, Lys 865, Lys 1000, Lys 1127, and Lys 1169
  • Modification sites at PhosphoSitePlus

Other Protein References for MTR Gene

Domains & Families for MTR Gene

Graphical View of Domain Structure for InterPro Entry

Q99707

UniProtKB/Swiss-Prot:

METH_HUMAN :
  • Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity).
  • Belongs to the vitamin-B12 dependent methionine synthase family.
Domain:
  • Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity).
  • Contains 1 AdoMet activation domain.
  • Contains 1 B12-binding domain.
  • Contains 1 B12-binding N-terminal domain.
  • Contains 1 Hcy-binding domain.
  • Contains 1 pterin-binding domain.
Family:
  • Belongs to the vitamin-B12 dependent methionine synthase family.
genes like me logo Genes that share domains with MTR: view

No data available for Gene Families for MTR Gene

Function for MTR Gene

Molecular function for MTR Gene

GENATLAS Biochemistry:
5-methyl tetrahydrofolate (THF),homocysteine methyltransferase,methionine synthase,140kDa,methylcobolamin dependent,sulfur aminoacid metabolism,no evidence of association with neural tube defects (NTD) in Netherlands and U.K.
UniProtKB/Swiss-Prot CatalyticActivity:
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.
UniProtKB/Swiss-Prot Function:
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

Enzyme Numbers (IUBMB) for MTR Gene

Gene Ontology (GO) - Molecular Function for MTR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008898 S-adenosylmethionine-homocysteine S-methyltransferase activity IEA --
GO:0031419 cobalamin binding IEA --
genes like me logo Genes that share ontologies with MTR: view
genes like me logo Genes that share phenotypes with MTR: view

Human Phenotype Ontology for MTR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MTR Gene

MGI Knock Outs for MTR:

Animal Model Products

No data available for Transcription Factor Targets and HOMER Transcription for MTR Gene

Localization for MTR Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTR Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MTR Gene COMPARTMENTS Subcellular localization image for MTR gene
Compartment Confidence
cytosol 5
lysosome 2
mitochondrion 2
nucleus 2
vacuole 2
extracellular 1
peroxisome 1
plasma membrane 1

No data available for Gene Ontology (GO) - Cellular Components for MTR Gene

Pathways & Interactions for MTR Gene

genes like me logo Genes that share pathways with MTR: view

UniProtKB/Swiss-Prot Q99707-METH_HUMAN

  • Pathway: Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.

Gene Ontology (GO) - Biological Process for MTR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000096 sulfur amino acid metabolic process TAS --
GO:0006766 vitamin metabolic process TAS --
GO:0006805 xenobiotic metabolic process TAS --
GO:0007399 nervous system development TAS 8968737
GO:0009086 methionine biosynthetic process IEA,IMP 23825108
genes like me logo Genes that share ontologies with MTR: view

No data available for SIGNOR curated interactions for MTR Gene

Drugs & Compounds for MTR Gene

(40) Drugs for MTR Gene - From: Novoseek, HMDB, DrugBank, and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hydroxocobalamin Approved Pharma Target, cofactor 227
Cyanocobalamin Approved Nutra Target, cofactor 227
L-Methionine Approved Nutra Target, product of 0
Tetrahydrofolic acid Approved Nutra Target, cofactor 0
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR, Cytotoxic agent 1444

(37) Additional Compounds for MTR Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cob(ii)alamin
  • Co(I)-Cobalamine
  • Cob(2)alamin
  • Cob(II)alamin
  • Cobinamide-Co(1+)
  • Vitamin B12r
14463-33-3
homocysteine
  • (+-)-homocysteine
  • (S)-2-amino-4-mercapto-Butanoate
  • (S)-2-amino-4-mercapto-Butanoic acid
  • 2-Amino-4-mercapto-Butanoate
  • 2-Amino-4-mercapto-Butanoic acid
454-29-5
5-Methyltetrahydropteroyltri-L-glutamate
  • 5-Methyltetrahydropteroyltri-L-glutamic acid
Cob(I)alamin
  • Cob(I)alamin
  • Cyanocobalamin
  • Hydrido-Cobalamin
  • Hydridocobalamin
  • Vitamin B12s
18534-66-2
Pterin
  • 2-Amino-1H-pteridin-4-one
  • 2-Amino-3H-pteridin-4-one
  • 2-Amino-4(1H)-pteridinone
  • 2-Amino-4(3H)-pteridinone
  • 2-Amino-4-hydroxypteridine
2236-60-4
genes like me logo Genes that share compounds with MTR: view

Transcripts for MTR Gene

Unigene Clusters for MTR Gene

5-methyltetrahydrofolate-homocysteine methyltransferase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MTR Gene

No ASD Table

Relevant External Links for MTR Gene

GeneLoc Exon Structure for
MTR
ECgene alternative splicing isoforms for
MTR

Expression for MTR Gene

mRNA expression in normal human tissues for MTR Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MTR Gene

This gene is overexpressed in Ovary (10.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for MTR Gene



SOURCE GeneReport for Unigene cluster for MTR Gene Hs.498187

mRNA Expression by UniProt/SwissProt for MTR Gene

Q99707-METH_HUMAN
Tissue specificity: Widely expressed. Expressed at the highest levels in pancreas, heart, brain, skeletal muscle and placenta. Expressed at lower levels in lung, liver and kidney.
genes like me logo Genes that share expression patterns with MTR: view

Protein tissue co-expression partners for MTR Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for MTR Gene

Orthologs for MTR Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MTR Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MTR 35
  • 89.62 (n)
  • 92.09 (a)
MTR 36
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MTR 35
  • 89.14 (n)
  • 90.91 (a)
MTR 36
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Mtr 35
  • 88.55 (n)
  • 92.09 (a)
Mtr 16
Mtr 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MTR 35
  • 99.55 (n)
  • 99.84 (a)
MTR 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mtr 35
  • 88.63 (n)
  • 92.49 (a)
oppossum
(Monodelphis domestica)
Mammalia MTR 36
  • 88 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MTR 36
  • 50 (a)
OneToOne
chicken
(Gallus gallus)
Aves MTR 35
  • 78.69 (n)
  • 84.1 (a)
MTR 36
  • 84 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MTR 36
  • 81 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100488827 35
  • 74.83 (n)
  • 81.3 (a)
zebrafish
(Danio rerio)
Actinopterygii mtr 35
  • 70.65 (n)
  • 77.91 (a)
MTR 36
  • 73 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea R03D7.1 37
  • 63 (a)
metr-1 35
  • 61.95 (n)
  • 64.36 (a)
metr-1 36
  • 64 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MHT1 38
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1103 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 68 (a)
OneToOne
Species with no ortholog for MTR:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MTR Gene

ENSEMBL:
Gene Tree for MTR (if available)
TreeFam:
Gene Tree for MTR (if available)

Paralogs for MTR Gene

(1) SIMAP similar genes for MTR Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with MTR: view

No data available for Paralogs for MTR Gene

Variants for MTR Gene

Sequence variations from dbSNP and Humsavar for MTR Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
VAR_004326 -
VAR_004327 -
rs1805087 - 236,885,200(+) ACAGG(A/G)CCATT reference, missense
VAR_004330 Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG)
VAR_004331 Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG)

Structural Variations from Database of Genomic Variants (DGV) for MTR Gene

Variant ID Type Subtype PubMed ID
nsv428335 CNV Gain 18775914
nsv5010 CNV Insertion 18451855
nsv5021 CNV Loss 18451855

Variation tolerance for MTR Gene

Residual Variation Intolerance Score: 20.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.97; 89.94% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MTR Gene

HapMap Linkage Disequilibrium report
MTR
Human Gene Mutation Database (HGMD)
MTR

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MTR Gene

Disorders for MTR Gene

MalaCards: The human disease database

(29) MalaCards diseases for MTR Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
homocystinuria-megaloblastic anemia, cblg complementation type
  • homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblg complementation type
neural tube defects, folate-sensitive
  • neural tube defects
vitamin b12 deficiency
  • cobalamin deficiency
homocystinuria
  • cbs deficiency
hyperhomocysteinemia
- elite association - COSMIC cancer census association via MalaCards
Search MTR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

METH_HUMAN
  • Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG) [MIM:250940]: An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. {ECO:0000269 PubMed:8968736, ECO:0000269 PubMed:8968737}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Neural tube defects, folate-sensitive (NTDFS) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. {ECO:0000269 PubMed:12375236}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Genatlas disease for MTR Gene

methylmalonic acidemia and homocystinuria,megaloblastic anemia with/without the cblG variant,characterized by neonatal seizures,severe developmental delay and hyperhomocysteinemia,cblG complementation groups no evidence of association with neural tube defects (NTD) in Netherlands and U.K.

Relevant External Links for MTR

Genetic Association Database (GAD)
MTR
Human Genome Epidemiology (HuGE) Navigator
MTR
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MTR
genes like me logo Genes that share disorders with MTR: view

Publications for MTR Gene

  1. Cloning, mapping and RNA analysis of the human methionine synthase gene. (PMID: 8968735) Li Y.N. … Kruger W.D. (Hum. Mol. Genet. 1996) 2 3 4 23 67
  2. Vitamin B12, folic acid, and the nervous system. (PMID: 17052662) Reynolds E. (Lancet Neurol 2006) 23 25 26
  3. Remethylation defects: guidelines for clinical diagnosis and treatment. (PMID: 9587031) Ogier de Baulny H. … Zittoun J. (Eur. J. Pediatr. 1998) 23 25 26
  4. Mechanism of conversion of human apo- to holomethionine synthase by various forms of cobalamin. (PMID: 1744096) Kolhouse J.F. … Allen R.H. (J. Biol. Chem. 1991) 23 25 26
  5. The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women. (PMID: 19760026) Tong S.Y. … Kwon Y.I. (Cancer Causes Control 2010) 3 23

Products for MTR Gene

Sources for MTR Gene

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