Q9Z2Q4 · METH_RAT

Function

function

Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:9219091, PubMed:9972236).
MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis (PubMed:9219091, PubMed:9972236).
Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate (By similarity).
The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (By similarity).

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
methylcob(III)alamin (UniProtKB | Rhea| CHEBI:28115 )

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
75 μM(6S)-5-methyl-5,6,7,8-tetrahydrofolate
1.7 μML-homocysteine

Pathway

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

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site248Zn2+ (UniProtKB | ChEBI)
Binding site311Zn2+ (UniProtKB | ChEBI)
Binding site312Zn2+ (UniProtKB | ChEBI)
Binding site370-372(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site437(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site458(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site525(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site567(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site573(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site579(6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI)
Binding site697methylcob(III)alamin (UniProtKB | ChEBI)
Binding site770-774methylcob(III)alamin (UniProtKB | ChEBI)
Binding site773Co (UniProtKB | ChEBI) of methylcob(III)alamin (UniProtKB | ChEBI); axial binding residue
Binding site818methylcob(III)alamin (UniProtKB | ChEBI)
Binding site822methylcob(III)alamin (UniProtKB | ChEBI)
Binding site874methylcob(III)alamin (UniProtKB | ChEBI)
Binding site962S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site1160S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site1215-1216S-adenosyl-L-methionine (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Molecular Functionamino acid binding
Molecular Functioncobalamin binding
Molecular Functionfolic acid binding
Molecular Functionmethionine synthase activity
Molecular Functionmethyltransferase activity
Molecular Functionzinc ion binding
Biological Processcellular response to methionine
Biological Processcobalamin metabolic process
Biological Processhomocysteine metabolic process
Biological Processmethionine biosynthetic process
Biological Processmethionine metabolic process
Biological Processmethylation
Biological Processtetrahydrofolate metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Methionine synthase
  • EC number
  • Short names
    MS
  • Alternative names
    • 5-methyltetrahydrofolate--homocysteine methyltransferase
    • Cobalamin-dependent methionine synthase
    • Vitamin-B12 dependent methionine synthase

Gene names

    • Name
      Mtr

Organism names

  • Taxonomic identifier
  • Strain
    • Wistar
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q9Z2Q4

Proteomes

Organism-specific databases

Subcellular Location

Keywords

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00003129021-1253Methionine synthase
Modified residue1252Phosphothreonine

Keywords

Proteomic databases

PTM databases

Interaction

Subunit

Monomer (PubMed:9219091).
Dimer. Forms a multiprotein complex with MMACHC, MMADHC and MTRR

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain6-326Hcy-binding
Domain359-620Pterin-binding
Domain650-747B12-binding N-terminal
Domain760-895B12-binding
Domain911-1253AdoMet activation

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).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,253
  • Mass (Da)
    139,164
  • Last updated
    1999-05-01 v1
  • Checksum
    96BD40B796EBD75B
MKKTLQDEIEAILRKRIMVLDGGMGTMIQRYKLSEENFQGQEFKDHSRPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTSIAQADYGLEHLAYRMNKCSADVARKAAEEITLQTGVKRFVAGSLGPTNKTLSVSPSVERPDYRNITFDELVEAYQEQAKGLLDGGVDILLIETIFDTANAKAALFALQKLFEENYASPRPIFISGTIVDKSGRTLSGQTGEAFVTSVSHSDPLCIGLNCALGAAEMRPFIETIGKCTTAYVLCYPNAGLPNTFGDYDETPAMMAMHLKDFAVDGLVNVVGGCCGSTPDHIREIAEAVKNCKPRVPPDSVFEGHMLLSGLEPFRIGPYTNFVNIGERCNVAGSKKFAKLIMAGNYEEALSVAKVQVEMGAQVLDINMDDGMLDGPSAMTKFCNFIASEPDIAKVPLCIDSSNFAVIEAGLKCCQGKCIVNSISLKEGEEDFLEKARKIKKFGAAVVVMAFDEEGQATETDVKVSVCTRAYHLLVEKVGFNPNDIIFDPNILTIGTGMEEHNLYAINFIHATRVIKETLPGVRISGGLSNLSFAFRGMDAIREAMHGVFLYHAIKFGMDMGIVNAGSLPVYDDIHKDLLQLCEDLIWNRDAEATEKLLRYAQTHGKGGKKVIQTDEWRNGSIEERLEYALVKGIEKHIVEDTEEARLNREKYPRPLNIIEGPLMNGMKVVGDLFGAGKMFLPQVIKSARVMKKAVGHLIPFMEKEREEARVLNGSVEEEDPYQGTIVLATVKGDVHDIGKNIVGVVLGCNNFRVIDLGVMTPCDKILQAALDHKADIIGLSGLITPSLDEMIFVAKEMERLAIKIPLLIGGATTSRTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDENLKDDYFEEILEEYEDIRQDHYESLKERKYLPLSQARKHSFHIDWLSEPHPVKPTFIGTQVFEDYNLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKAVGEEARKVYEDAQNMLSILISRKKLRARGVVGFWPAQSVQDDIHLYAEGAVPQAAEPIATFYGLRQQAEKDSSSTDPYHCLSDFVAPLHSGVRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHERVRRELWAYCGSEQLGVTDLRKLRYEGIRPAPGYPSQPDHTEKLTMWRLANIEQATGIRLTESLAMAPASAVSGLYFSNVKSKYFAVGKISKDQIEDYALRKNMSVAEVEKWLGPILGYDTD

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
G3V8A4G3V8A4_RATMtr1253

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF034214
EMBL· GenBank· DDBJ
AAD05384.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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