Q9Z2Q4 · METH_RAT
- ProteinMethionine synthase
- GeneMtr
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1253 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionineThis reaction proceeds in the forward direction.
Cofactor
Protein has several cofactor binding sites:
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 μM | L-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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 248 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 311 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 312 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 370-372 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: GSK | ||||||
Binding site | 437 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 458 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 525 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 567 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 573 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 579 | (6S)-5,6,7,8-tetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 697 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 770-774 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: GDVHD | ||||||
Binding site | 773 | Co (UniProtKB | ChEBI) of methylcob(III)alamin (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: H | ||||||
Binding site | 818 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 822 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 874 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 962 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1160 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1215-1216 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: YF |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | amino acid binding | |
Molecular Function | cobalamin binding | |
Molecular Function | folic acid binding | |
Molecular Function | methionine synthase activity | |
Molecular Function | methyltransferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | cellular response to methionine | |
Biological Process | cobalamin metabolic process | |
Biological Process | homocysteine metabolic process | |
Biological Process | methionine biosynthetic process | |
Biological Process | methionine metabolic process | |
Biological Process | methylation | |
Biological Process | tetrahydrofolate metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMethionine synthase
- EC number
- Short namesMS
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ9Z2Q4
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000312902 | 1-1253 | Methionine synthase | |||
Sequence: MKKTLQDEIEAILRKRIMVLDGGMGTMIQRYKLSEENFQGQEFKDHSRPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTSIAQADYGLEHLAYRMNKCSADVARKAAEEITLQTGVKRFVAGSLGPTNKTLSVSPSVERPDYRNITFDELVEAYQEQAKGLLDGGVDILLIETIFDTANAKAALFALQKLFEENYASPRPIFISGTIVDKSGRTLSGQTGEAFVTSVSHSDPLCIGLNCALGAAEMRPFIETIGKCTTAYVLCYPNAGLPNTFGDYDETPAMMAMHLKDFAVDGLVNVVGGCCGSTPDHIREIAEAVKNCKPRVPPDSVFEGHMLLSGLEPFRIGPYTNFVNIGERCNVAGSKKFAKLIMAGNYEEALSVAKVQVEMGAQVLDINMDDGMLDGPSAMTKFCNFIASEPDIAKVPLCIDSSNFAVIEAGLKCCQGKCIVNSISLKEGEEDFLEKARKIKKFGAAVVVMAFDEEGQATETDVKVSVCTRAYHLLVEKVGFNPNDIIFDPNILTIGTGMEEHNLYAINFIHATRVIKETLPGVRISGGLSNLSFAFRGMDAIREAMHGVFLYHAIKFGMDMGIVNAGSLPVYDDIHKDLLQLCEDLIWNRDAEATEKLLRYAQTHGKGGKKVIQTDEWRNGSIEERLEYALVKGIEKHIVEDTEEARLNREKYPRPLNIIEGPLMNGMKVVGDLFGAGKMFLPQVIKSARVMKKAVGHLIPFMEKEREEARVLNGSVEEEDPYQGTIVLATVKGDVHDIGKNIVGVVLGCNNFRVIDLGVMTPCDKILQAALDHKADIIGLSGLITPSLDEMIFVAKEMERLAIKIPLLIGGATTSRTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDENLKDDYFEEILEEYEDIRQDHYESLKERKYLPLSQARKHSFHIDWLSEPHPVKPTFIGTQVFEDYNLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKAVGEEARKVYEDAQNMLSILISRKKLRARGVVGFWPAQSVQDDIHLYAEGAVPQAAEPIATFYGLRQQAEKDSSSTDPYHCLSDFVAPLHSGVRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHERVRRELWAYCGSEQLGVTDLRKLRYEGIRPAPGYPSQPDHTEKLTMWRLANIEQATGIRLTESLAMAPASAVSGLYFSNVKSKYFAVGKISKDQIEDYALRKNMSVAEVEKWLGPILGYDTD | ||||||
Modified residue | 1252 | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 6-326 | Hcy-binding | ||||
Sequence: QDEIEAILRKRIMVLDGGMGTMIQRYKLSEENFQGQEFKDHSRPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTSIAQADYGLEHLAYRMNKCSADVARKAAEEITLQTGVKRFVAGSLGPTNKTLSVSPSVERPDYRNITFDELVEAYQEQAKGLLDGGVDILLIETIFDTANAKAALFALQKLFEENYASPRPIFISGTIVDKSGRTLSGQTGEAFVTSVSHSDPLCIGLNCALGAAEMRPFIETIGKCTTAYVLCYPNAGLPNTFGDYDETPAMMAMHLKDFAVDGLVNVVGGCCGSTPDHIREIAEAV | ||||||
Domain | 359-620 | Pterin-binding | ||||
Sequence: FVNIGERCNVAGSKKFAKLIMAGNYEEALSVAKVQVEMGAQVLDINMDDGMLDGPSAMTKFCNFIASEPDIAKVPLCIDSSNFAVIEAGLKCCQGKCIVNSISLKEGEEDFLEKARKIKKFGAAVVVMAFDEEGQATETDVKVSVCTRAYHLLVEKVGFNPNDIIFDPNILTIGTGMEEHNLYAINFIHATRVIKETLPGVRISGGLSNLSFAFRGMDAIREAMHGVFLYHAIKFGMDMGIVNAGSLPVYDDIHKDLLQLCE | ||||||
Domain | 650-747 | B12-binding N-terminal | ||||
Sequence: QTDEWRNGSIEERLEYALVKGIEKHIVEDTEEARLNREKYPRPLNIIEGPLMNGMKVVGDLFGAGKMFLPQVIKSARVMKKAVGHLIPFMEKEREEAR | ||||||
Domain | 760-895 | B12-binding | ||||
Sequence: QGTIVLATVKGDVHDIGKNIVGVVLGCNNFRVIDLGVMTPCDKILQAALDHKADIIGLSGLITPSLDEMIFVAKEMERLAIKIPLLIGGATTSRTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDENLKDDYFE | ||||||
Domain | 911-1253 | AdoMet activation | ||||
Sequence: SLKERKYLPLSQARKHSFHIDWLSEPHPVKPTFIGTQVFEDYNLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKAVGEEARKVYEDAQNMLSILISRKKLRARGVVGFWPAQSVQDDIHLYAEGAVPQAAEPIATFYGLRQQAEKDSSSTDPYHCLSDFVAPLHSGVRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHERVRRELWAYCGSEQLGVTDLRKLRYEGIRPAPGYPSQPDHTEKLTMWRLANIEQATGIRLTESLAMAPASAVSGLYFSNVKSKYFAVGKISKDQIEDYALRKNMSVAEVEKWLGPILGYDTD |
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
Belongs to the vitamin-B12 dependent methionine synthase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,253
- Mass (Da)139,164
- Last updated1999-05-01 v1
- Checksum96BD40B796EBD75B
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
G3V8A4 | G3V8A4_RAT | Mtr | 1253 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF034214 EMBL· GenBank· DDBJ | AAD05384.1 EMBL· GenBank· DDBJ | mRNA |