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Entry version 198 (13 Nov 2019)
Sequence version 2 (01 Jul 1997)
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Protein

Methionine synthase

Gene

MTR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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).By similarity

Miscellaneous

L-homocysteine is bound via the zinc atom.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Protein has several cofactor binding sites:

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: L-methionine biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes L-methionine from L-homocysteine (MetH route).
Proteins known to be involved in this subpathway in this organism are:
  1. Methionine synthase, Methionine synthase (MTR), Methionine synthase (MTR)
This subpathway is part of the pathway L-methionine biosynthesis via de novo pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-methionine from L-homocysteine (MetH route), the pathway L-methionine biosynthesis via de novo pathway and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi260ZincPROSITE-ProRule annotation1
Metal bindingi323ZincPROSITE-ProRule annotation1
Metal bindingi324ZincPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei449SubstrateCombined sources1 Publication1
Binding sitei470SubstrateCombined sources1 Publication1
Binding sitei537SubstrateCombined sources1 Publication1
Binding sitei579SubstrateCombined sources1 Publication1
Binding sitei585SubstrateCombined sources1 Publication1
Binding sitei591SubstrateCombined sources1 Publication1
Metal bindingi785Cobalt (cobalamin axial ligand)By similarity1
Binding sitei830CobalaminBy similarity1
Binding sitei974S-adenosyl-L-methionineBy similarity1
Binding sitei1172S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei1176Cobalamin; via carbonyl oxygenBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionMethyltransferase, Transferase
Biological processAmino-acid biosynthesis, Methionine biosynthesis
LigandCobalamin, Cobalt, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

More...
BioCyci
MetaCyc:HS04076-MONOMER

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-156581 Methylation
R-HSA-1614635 Sulfur amino acid metabolism
R-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-3359467 Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
R-HSA-3359469 Defective MTR causes methylmalonic aciduria and homocystinuria type cblG

SIGNOR Signaling Network Open Resource

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SIGNORi
Q99707

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00051;UER00081

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Methionine synthase (EC:2.1.1.13)
Alternative name(s):
5-methyltetrahydrofolate--homocysteine methyltransferase
Vitamin-B12 dependent methionine synthase
Short name:
MS
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MTR
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:7468 MTR

Online Mendelian Inheritance in Man (OMIM)

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MIMi
156570 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q99707

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_004328881Missing in HMAG. 2 Publications1
Natural variantiVAR_004330920H → D in HMAG. 1 PublicationCorresponds to variant dbSNP:rs121913579EnsemblClinVar.1
Natural variantiVAR_0043311173P → L in HMAG. 1 PublicationCorresponds to variant dbSNP:rs121913578EnsemblClinVar.1
Neural tube defects, folate-sensitive (NTDFS)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionThe most common NTDs are open spina bifida (myelomeningocele) and anencephaly.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi963D → E: Decreases binding to MTRR; when associated with N-1071. 1 Publication1
Mutagenesisi1071K → N: Decreases binding to MTRR; when associated with E-963. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
4548

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...
GeneReviewsi
MTR

MalaCards human disease database

More...
MalaCardsi
MTR
MIMi250940 phenotype
601634 phenotype
603174 phenotype

Open Targets

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OpenTargetsi
ENSG00000116984

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
2170 Methylcobalamin deficiency type cblG

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA31272

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
Q99707

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL2150844

Drug and drug target database

More...
DrugBanki
DB00115 Cyanocobalamin
DB00200 Hydroxocobalamin
DB11256 Levomefolic acid
DB00134 Methionine
DB00116 Tetrahydrofolic acid
DB11590 Thimerosal

DrugCentral

More...
DrugCentrali
Q99707

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MTR

Domain mapping of disease mutations (DMDM)

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DMDMi
2842762

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002045301 – 1265Methionine synthaseAdd BLAST1265

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1264PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q99707

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q99707

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q99707

MaxQB - The MaxQuant DataBase

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MaxQBi
Q99707

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q99707

PeptideAtlas

More...
PeptideAtlasi
Q99707

PRoteomics IDEntifications database

More...
PRIDEi
Q99707

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
7238
78423 [Q99707-1]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q99707

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q99707

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed. Expressed at the highest levels in pancreas, heart, brain, skeletal muscle and placenta. Expressed at lower levels in lung, liver and kidney.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000116984 Expressed in 237 organ(s), highest expression level in metanephros

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q99707 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q99707 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA044474
HPA054915

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer (PubMed:17288554). Dimer (PubMed:17288554). Mainly monomer.

Interacts with MTRR (PubMed:17288554).

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
Q9Y4U13EBI-1045782,EBI-9775184

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
110642, 38 interactors

Database of interacting proteins

More...
DIPi
DIP-40306N

Protein interaction database and analysis system

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IntActi
Q99707, 17 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000355536

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q99707

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q99707

Database of comparative protein structure models

More...
ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
Q99707

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini19 – 338Hcy-bindingPROSITE-ProRule annotationAdd BLAST320
Domaini371 – 632Pterin-bindingPROSITE-ProRule annotationAdd BLAST262
Domaini662 – 759B12-binding N-terminalPROSITE-ProRule annotationAdd BLAST98
Domaini772 – 907B12-bindingPROSITE-ProRule annotationAdd BLAST136
Domaini923 – 1265AdoMet activationPROSITE-ProRule annotationAdd BLAST343

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni382 – 384Substrate bindingCombined sources3
Regioni860 – 861Cobalamin-bindingBy similarity2
Regioni1227 – 1228S-adenosyl-L-methionine bindingBy similarity2

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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).By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG1579 Eukaryota
COG0646 LUCA
COG1410 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00420000029824

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000251409

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q99707

KEGG Orthology (KO)

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KOi
K00548

Identification of Orthologs from Complete Genome Data

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OMAi
ADCIAMS

Database of Orthologous Groups

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OrthoDBi
731388at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q99707

TreeFam database of animal gene trees

More...
TreeFami
TF312829

Family and domain databases

Conserved Domains Database

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CDDi
cd02069 methionine_synthase_B12_BD, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
1.10.1240.10, 1 hit
3.10.196.10, 1 hit
3.20.20.20, 1 hit
3.20.20.330, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR003759 Cbl-bd_cap
IPR006158 Cobalamin-bd
IPR036724 Cobalamin-bd_sf
IPR011005 Dihydropteroate_synth-like
IPR003726 HCY_dom
IPR036589 HCY_dom_sf
IPR033706 Met_synthase_B12-bd
IPR011822 MetH
IPR036594 Meth_synthase_dom
IPR000489 Pterin-binding_dom
IPR004223 VitB12-dep_Met_synth_activ_dom
IPR037010 VitB12-dep_Met_synth_activ_sf

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF02310 B12-binding, 1 hit
PF02607 B12-binding_2, 1 hit
PF02965 Met_synt_B12, 1 hit
PF00809 Pterin_bind, 1 hit
PF02574 S-methyl_trans, 1 hit

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF000381 MetH, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM01018 B12-binding_2, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF47644 SSF47644, 1 hit
SSF51717 SSF51717, 1 hit
SSF52242 SSF52242, 1 hit
SSF56507 SSF56507, 1 hit
SSF82282 SSF82282, 1 hit

TIGRFAMs; a protein family database

More...
TIGRFAMsi
TIGR02082 metH, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50974 ADOMET_ACTIVATION, 1 hit
PS51332 B12_BINDING, 1 hit
PS51337 B12_BINDING_NTER, 1 hit
PS50970 HCY, 1 hit
PS50972 PTERIN_BINDING, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q99707-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSPALQDLSQ PEGLKKTLRD EINAILQKRI MVLDGGMGTM IQREKLNEEH
60 70 80 90 100
FRGQEFKDHA RPLKGNNDIL SITQPDVIYQ IHKEYLLAGA DIIETNTFSS
110 120 130 140 150
TSIAQADYGL EHLAYRMNMC SAGVARKAAE EVTLQTGIKR FVAGALGPTN
160 170 180 190 200
KTLSVSPSVE RPDYRNITFD ELVEAYQEQA KGLLDGGVDI LLIETIFDTA
210 220 230 240 250
NAKAALFALQ NLFEEKYAPR PIFISGTIVD KSGRTLSGQT GEGFVISVSH
260 270 280 290 300
GEPLCIGLNC ALGAAEMRPF IEIIGKCTTA YVLCYPNAGL PNTFGDYDET
310 320 330 340 350
PSMMAKHLKD FAMDGLVNIV GGCCGSTPDH IREIAEAVKN CKPRVPPATA
360 370 380 390 400
FEGHMLLSGL EPFRIGPYTN FVNIGERCNV AGSRKFAKLI MAGNYEEALC
410 420 430 440 450
VAKVQVEMGA QVLDVNMDDG MLDGPSAMTR FCNLIASEPD IAKVPLCIDS
460 470 480 490 500
SNFAVIEAGL KCCQGKCIVN SISLKEGEDD FLEKARKIKK YGAAMVVMAF
510 520 530 540 550
DEEGQATETD TKIRVCTRAY HLLVKKLGFN PNDIIFDPNI LTIGTGMEEH
560 570 580 590 600
NLYAINFIHA TKVIKETLPG ARISGGLSNL SFSFRGMEAI REAMHGVFLY
610 620 630 640 650
HAIKSGMDMG IVNAGNLPVY DDIHKELLQL CEDLIWNKDP EATEKLLRYA
660 670 680 690 700
QTQGTGGKKV IQTDEWRNGP VEERLEYALV KGIEKHIIED TEEARLNQKK
710 720 730 740 750
YPRPLNIIEG PLMNGMKIVG DLFGAGKMFL PQVIKSARVM KKAVGHLIPF
760 770 780 790 800
MEKEREETRV LNGTVEEEDP YQGTIVLATV KGDVHDIGKN IVGVVLGCNN
810 820 830 840 850
FRVIDLGVMT PCDKILKAAL DHKADIIGLS GLITPSLDEM IFVAKEMERL
860 870 880 890 900
AIRIPLLIGG ATTSKTHTAV KIAPRYSAPV IHVLDASKSV VVCSQLLDEN
910 920 930 940 950
LKDEYFEEIM EEYEDIRQDH YESLKERRYL PLSQARKSGF QMDWLSEPHP
960 970 980 990 1000
VKPTFIGTQV FEDYDLQKLV DYIDWKPFFD VWQLRGKYPN RGFPKIFNDK
1010 1020 1030 1040 1050
TVGGEARKVY DDAHNMLNTL ISQKKLRARG VVGFWPAQSI QDDIHLYAEA
1060 1070 1080 1090 1100
AVPQAAEPIA TFYGLRQQAE KDSASTEPYY CLSDFIAPLH SGIRDYLGLF
1110 1120 1130 1140 1150
AVACFGVEEL SKAYEDDGDD YSSIMVKALG DRLAEAFAEE LHERVRRELW
1160 1170 1180 1190 1200
AYCGSEQLDV ADLRRLRYKG IRPAPGYPSQ PDHTEKLTMW RLADIEQSTG
1210 1220 1230 1240 1250
IRLTESLAMA PASAVSGLYF SNLKSKYFAV GKISKDQVED YALRKNISVA
1260
EVEKWLGPIL GYDTD
Length:1,265
Mass (Da):140,527
Last modified:July 1, 1997 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB04C26BCBE9A57C2
GO
Isoform 2 (identifier: Q99707-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     682-732: Missing.

Note: No experimental confirmation available.
Show »
Length:1,214
Mass (Da):134,793
Checksum:i2E568CD852B22E8C
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A494C1A2A0A494C1A2_HUMAN
Methionine synthase
MTR
380Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B1ANE3B1ANE3_HUMAN
Methionine synthase
MTR
819Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C064A0A494C064_HUMAN
Methionine synthase
MTR
264Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05003352R → Q. Corresponds to variant dbSNP:rs12749581EnsemblClinVar.1
Natural variantiVAR_00432661R → K1 Publication1
Natural variantiVAR_004327255C → Y1 PublicationCorresponds to variant dbSNP:rs1140598Ensembl.1
Natural variantiVAR_061338314D → N. Corresponds to variant dbSNP:rs2229274EnsemblClinVar.1
Natural variantiVAR_004328881Missing in HMAG. 2 Publications1
Natural variantiVAR_004329919D → G4 PublicationsCorresponds to variant dbSNP:rs1805087EnsemblClinVar.1
Natural variantiVAR_004330920H → D in HMAG. 1 PublicationCorresponds to variant dbSNP:rs121913579EnsemblClinVar.1
Natural variantiVAR_0043311173P → L in HMAG. 1 PublicationCorresponds to variant dbSNP:rs121913578EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_057283682 – 732Missing in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U71285 mRNA Translation: AAC51188.1
U75743 mRNA Translation: AAB58906.1
U73338 mRNA Translation: AAB39704.1
AL359185 Genomic DNA No translation available.
AL359259 Genomic DNA No translation available.
CH471098 Genomic DNA Translation: EAW70066.1
BC130616 mRNA Translation: AAI30617.1
BC136440 mRNA Translation: AAI36441.1
BC144095 mRNA Translation: AAI44096.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS1614.1 [Q99707-1]
CCDS73054.1 [Q99707-2]

NCBI Reference Sequences

More...
RefSeqi
NP_000245.2, NM_000254.2 [Q99707-1]
NP_001278868.1, NM_001291939.1 [Q99707-2]
NP_001278869.1, NM_001291940.1

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000366577; ENSP00000355536; ENSG00000116984 [Q99707-1]
ENST00000535889; ENSP00000441845; ENSG00000116984 [Q99707-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
4548

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:4548

UCSC genome browser

More...
UCSCi
uc001hyi.5 human [Q99707-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

5-methyltetrahydrofolate-homocysteine methyltransferase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71285 mRNA Translation: AAC51188.1
U75743 mRNA Translation: AAB58906.1
U73338 mRNA Translation: AAB39704.1
AL359185 Genomic DNA No translation available.
AL359259 Genomic DNA No translation available.
CH471098 Genomic DNA Translation: EAW70066.1
BC130616 mRNA Translation: AAI30617.1
BC136440 mRNA Translation: AAI36441.1
BC144095 mRNA Translation: AAI44096.1
CCDSiCCDS1614.1 [Q99707-1]
CCDS73054.1 [Q99707-2]
RefSeqiNP_000245.2, NM_000254.2 [Q99707-1]
NP_001278868.1, NM_001291939.1 [Q99707-2]
NP_001278869.1, NM_001291940.1

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2O2KX-ray1.60A/B925-1265[»]
4CCZX-ray2.70A16-657[»]
SMRiQ99707
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi110642, 38 interactors
DIPiDIP-40306N
IntActiQ99707, 17 interactors
STRINGi9606.ENSP00000355536

Chemistry databases

BindingDBiQ99707
ChEMBLiCHEMBL2150844
DrugBankiDB00115 Cyanocobalamin
DB00200 Hydroxocobalamin
DB11256 Levomefolic acid
DB00134 Methionine
DB00116 Tetrahydrofolic acid
DB11590 Thimerosal
DrugCentraliQ99707

PTM databases

iPTMnetiQ99707
PhosphoSitePlusiQ99707

Polymorphism and mutation databases

BioMutaiMTR
DMDMi2842762

Proteomic databases

EPDiQ99707
jPOSTiQ99707
MassIVEiQ99707
MaxQBiQ99707
PaxDbiQ99707
PeptideAtlasiQ99707
PRIDEiQ99707
ProteomicsDBi7238
78423 [Q99707-1]

Genome annotation databases

EnsembliENST00000366577; ENSP00000355536; ENSG00000116984 [Q99707-1]
ENST00000535889; ENSP00000441845; ENSG00000116984 [Q99707-2]
GeneIDi4548
KEGGihsa:4548
UCSCiuc001hyi.5 human [Q99707-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4548
DisGeNETi4548

GeneCards: human genes, protein and diseases

More...
GeneCardsi
MTR
GeneReviewsiMTR
HGNCiHGNC:7468 MTR
HPAiHPA044474
HPA054915
MalaCardsiMTR
MIMi156570 gene
250940 phenotype
601634 phenotype
603174 phenotype
neXtProtiNX_Q99707
OpenTargetsiENSG00000116984
Orphaneti2170 Methylcobalamin deficiency type cblG
PharmGKBiPA31272

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1579 Eukaryota
COG0646 LUCA
COG1410 LUCA
GeneTreeiENSGT00420000029824
HOGENOMiHOG000251409
InParanoidiQ99707
KOiK00548
OMAiADCIAMS
OrthoDBi731388at2759
PhylomeDBiQ99707
TreeFamiTF312829

Enzyme and pathway databases

UniPathwayiUPA00051;UER00081
BioCyciMetaCyc:HS04076-MONOMER
ReactomeiR-HSA-156581 Methylation
R-HSA-1614635 Sulfur amino acid metabolism
R-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-3359467 Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
R-HSA-3359469 Defective MTR causes methylmalonic aciduria and homocystinuria type cblG
SIGNORiQ99707

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
MTR human
EvolutionaryTraceiQ99707

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Methionine_synthase

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
4548
PharosiQ99707

Protein Ontology

More...
PROi
PR:Q99707

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000116984 Expressed in 237 organ(s), highest expression level in metanephros
ExpressionAtlasiQ99707 baseline and differential
GenevisibleiQ99707 HS

Family and domain databases

CDDicd02069 methionine_synthase_B12_BD, 1 hit
Gene3Di1.10.1240.10, 1 hit
3.10.196.10, 1 hit
3.20.20.20, 1 hit
3.20.20.330, 1 hit
InterProiView protein in InterPro
IPR003759 Cbl-bd_cap
IPR006158 Cobalamin-bd
IPR036724 Cobalamin-bd_sf
IPR011005 Dihydropteroate_synth-like
IPR003726 HCY_dom
IPR036589 HCY_dom_sf
IPR033706 Met_synthase_B12-bd
IPR011822 MetH
IPR036594 Meth_synthase_dom
IPR000489 Pterin-binding_dom
IPR004223 VitB12-dep_Met_synth_activ_dom
IPR037010 VitB12-dep_Met_synth_activ_sf
PfamiView protein in Pfam
PF02310 B12-binding, 1 hit
PF02607 B12-binding_2, 1 hit
PF02965 Met_synt_B12, 1 hit
PF00809 Pterin_bind, 1 hit
PF02574 S-methyl_trans, 1 hit
PIRSFiPIRSF000381 MetH, 1 hit
SMARTiView protein in SMART
SM01018 B12-binding_2, 1 hit
SUPFAMiSSF47644 SSF47644, 1 hit
SSF51717 SSF51717, 1 hit
SSF52242 SSF52242, 1 hit
SSF56507 SSF56507, 1 hit
SSF82282 SSF82282, 1 hit
TIGRFAMsiTIGR02082 metH, 1 hit
PROSITEiView protein in PROSITE
PS50974 ADOMET_ACTIVATION, 1 hit
PS51332 B12_BINDING, 1 hit
PS51337 B12_BINDING_NTER, 1 hit
PS50970 HCY, 1 hit
PS50972 PTERIN_BINDING, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiMETH_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q99707
Secondary accession number(s): A1L4N8
, A9Z1W4, B7ZLW7, B9EGF7, Q99713, Q99723
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: November 13, 2019
This is version 198 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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