Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Methionine synthase

Gene

metH

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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.

Miscellaneous

L-homocysteine is bound via the zinc atom.

Catalytic activityi

5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.

Cofactori

Protein has several cofactor binding sites:

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 (metH)
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
Metal bindingi247Zinc1
Metal bindingi310Zinc1
Metal bindingi311Zinc1
Metal bindingi759Cobalt (cobalamin axial ligand)1 Publication1
Binding sitei804Cobalamin2 Publications1
Binding sitei946S-adenosyl-L-methionine1 Publication1
Binding sitei1134S-adenosyl-L-methionine; via carbonyl oxygen1 Publication1
Binding sitei1138Cobalamin; via carbonyl oxygen2 Publications1

GO - Molecular functioni

  • cobalamin binding Source: BHF-UCL
  • methionine synthase activity Source: BHF-UCL
  • protein methyltransferase activity Source: BHF-UCL
  • zinc ion binding Source: EcoCyc

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BioCyciEcoCyc:HOMOCYSMETB12-MONOMER
MetaCyc:HOMOCYSMETB12-MONOMER
BRENDAi2.1.1.13 2026
UniPathwayi
UPA00051;UER00081

Names & Taxonomyi

Protein namesi
Recommended name:
Methionine synthase (EC:2.1.1.13)
Alternative name(s):
5-methyltetrahydrofolate--homocysteine methyltransferase
Methionine synthase, vitamin-B12-dependent
Short name:
MS
Gene namesi
Name:metH
Ordered Locus Names:b4019, JW3979
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10587 metH

Subcellular locationi

GO - Cellular componenti

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi310C → A or S: Loss of zinc binding. Loss of catalytic activity. 1 Publication1
Mutagenesisi311C → A or S: Loss of zinc binding. Loss of catalytic activity. 1 Publication1
Mutagenesisi757D → E: Decreases activity by about 70%. 1 Publication1
Mutagenesisi757D → N: Decreases activity by about 45%. 1 Publication1
Mutagenesisi759H → G: Loss of catalytic activity. 1 Publication1
Mutagenesisi810S → A: Decreases activity by about 40%. 1 Publication1

Chemistry databases

DrugBankiDB03614 Methylcobalamin

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002045322 – 1227Methionine synthaseAdd BLAST1226

Proteomic databases

EPDiP13009
PaxDbiP13009
PRIDEiP13009

2D gel databases

SWISS-2DPAGEiP13009

Interactioni

Protein-protein interaction databases

BioGridi4263452, 39 interactors
IntActiP13009, 13 interactors
STRINGi316385.ECDH10B_4208

Structurei

Secondary structure

11227
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP13009
SMRiP13009
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13009

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 325Hcy-bindingPROSITE-ProRule annotationAdd BLAST324
Domaini356 – 617Pterin-bindingPROSITE-ProRule annotationAdd BLAST262
Domaini650 – 744B12-binding N-terminalPROSITE-ProRule annotationAdd BLAST95
Domaini746 – 881B12-bindingPROSITE-ProRule annotationAdd BLAST136
Domaini897 – 1227AdoMet activationPROSITE-ProRule annotationAdd BLAST331

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni834 – 835Cobalamin-binding2
Regioni1189 – 1190S-adenosyl-L-methionine binding2

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.1 Publication

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG4105C3R Bacteria
COG0646 LUCA
COG1410 LUCA
HOGENOMiHOG000251409
InParanoidiP13009
KOiK00548
PhylomeDBiP13009

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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P13009-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSSKVEQLRA QLNERILVLD GGMGTMIQSY RLNEADFRGE RFADWPCDLK
60 70 80 90 100
GNNDLLVLSK PEVIAAIHNA YFEAGADIIE TNTFNSTTIA MADYQMESLS
110 120 130 140 150
AEINFAAAKL ARACADEWTA RTPEKPRYVA GVLGPTNRTA SISPDVNDPA
160 170 180 190 200
FRNITFDGLV AAYRESTKAL VEGGADLILI ETVFDTLNAK AAVFAVKTEF
210 220 230 240 250
EALGVELPIM ISGTITDASG RTLSGQTTEA FYNSLRHAEA LTFGLNCALG
260 270 280 290 300
PDELRQYVQE LSRIAECYVT AHPNAGLPNA FGEYDLDADT MAKQIREWAQ
310 320 330 340 350
AGFLNIVGGC CGTTPQHIAA MSRAVEGLAP RKLPEIPVAC RLSGLEPLNI
360 370 380 390 400
GEDSLFVNVG ERTNVTGSAK FKRLIKEEKY SEALDVARQQ VENGAQIIDI
410 420 430 440 450
NMDEGMLDAE AAMVRFLNLI AGEPDIARVP IMIDSSKWDV IEKGLKCIQG
460 470 480 490 500
KGIVNSISMK EGVDAFIHHA KLLRRYGAAV VVMAFDEQGQ ADTRARKIEI
510 520 530 540 550
CRRAYKILTE EVGFPPEDII FDPNIFAVAT GIEEHNNYAQ DFIGACEDIK
560 570 580 590 600
RELPHALISG GVSNVSFSFR GNDPVREAIH AVFLYYAIRN GMDMGIVNAG
610 620 630 640 650
QLAIYDDLPA ELRDAVEDVI LNRRDDGTER LLELAEKYRG SKTDDTANAQ
660 670 680 690 700
QAEWRSWEVN KRLEYSLVKG ITEFIEQDTE EARQQATRPI EVIEGPLMDG
710 720 730 740 750
MNVVGDLFGE GKMFLPQVVK SARVMKQAVA YLEPFIEASK EQGKTNGKMV
760 770 780 790 800
IATVKGDVHD IGKNIVGVVL QCNNYEIVDL GVMVPAEKIL RTAKEVNADL
810 820 830 840 850
IGLSGLITPS LDEMVNVAKE MERQGFTIPL LIGGATTSKA HTAVKIEQNY
860 870 880 890 900
SGPTVYVQNA SRTVGVVAAL LSDTQRDDFV ARTRKEYETV RIQHGRKKPR
910 920 930 940 950
TPPVTLEAAR DNDFAFDWQA YTPPVAHRLG VQEVEASIET LRNYIDWTPF
960 970 980 990 1000
FMTWSLAGKY PRILEDEVVG VEAQRLFKDA NDMLDKLSAE KTLNPRGVVG
1010 1020 1030 1040 1050
LFPANRVGDD IEIYRDETRT HVINVSHHLR QQTEKTGFAN YCLADFVAPK
1060 1070 1080 1090 1100
LSGKADYIGA FAVTGGLEED ALADAFEAQH DDYNKIMVKA LADRLAEAFA
1110 1120 1130 1140 1150
EYLHERVRKV YWGYAPNENL SNEELIRENY QGIRPAPGYP ACPEHTEKAT
1160 1170 1180 1190 1200
IWELLEVEKH TGMKLTESFA MWPGASVSGW YFSHPDSKYY AVAQIQRDQV
1210 1220
EDYARRKGMS VTEVERWLAP NLGYDAD
Length:1,227
Mass (Da):135,997
Last modified:January 23, 2007 - v5
Checksum:i91F0CAA1E9127D9A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti113A → R (PubMed:2185137).Curated1
Sequence conflicti113A → R (PubMed:2668277).Curated1
Sequence conflicti641S → T (PubMed:2185137).Curated1
Sequence conflicti641S → T (PubMed:2668277).Curated1
Sequence conflicti1079 – 1080QH → HD in CAA34601 (PubMed:2185137).Curated2
Sequence conflicti1195 – 1227IQRDQ…GYDAD → TSARSG in CAA34601 (PubMed:2185137).CuratedAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16584 Genomic DNA Translation: CAA34601.1
J04975 Unassigned DNA Translation: AAA02995.1
U00006 Genomic DNA Translation: AAC43113.1
U00096 Genomic DNA Translation: AAC76989.1
AP009048 Genomic DNA Translation: BAE78021.1
PIRiB65209 XYECMH
RefSeqiNP_418443.1, NC_000913.3
WP_000096011.1, NZ_LN832404.1

Genome annotation databases

EnsemblBacteriaiAAC76989; AAC76989; b4019
BAE78021; BAE78021; BAE78021
GeneIDi948522
KEGGiecj:JW3979
eco:b4019
PATRICifig|511145.12.peg.4132

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16584 Genomic DNA Translation: CAA34601.1
J04975 Unassigned DNA Translation: AAA02995.1
U00006 Genomic DNA Translation: AAC43113.1
U00096 Genomic DNA Translation: AAC76989.1
AP009048 Genomic DNA Translation: BAE78021.1
PIRiB65209 XYECMH
RefSeqiNP_418443.1, NC_000913.3
WP_000096011.1, NZ_LN832404.1

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BMTX-ray3.00A/B651-896[»]
1K7YX-ray3.00A651-1227[»]
1K98X-ray3.75A651-1227[»]
1MSKX-ray1.80A897-1227[»]
3BULX-ray2.30A649-1227[»]
3IV9X-ray3.25A649-1227[»]
3IVAX-ray2.70A649-1227[»]
6BDYX-ray1.51A897-1227[»]
6BM5X-ray1.50A897-1227[»]
6BM6X-ray1.50A897-1227[»]
ProteinModelPortaliP13009
SMRiP13009
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4263452, 39 interactors
IntActiP13009, 13 interactors
STRINGi316385.ECDH10B_4208

Chemistry databases

DrugBankiDB03614 Methylcobalamin

2D gel databases

SWISS-2DPAGEiP13009

Proteomic databases

EPDiP13009
PaxDbiP13009
PRIDEiP13009

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76989; AAC76989; b4019
BAE78021; BAE78021; BAE78021
GeneIDi948522
KEGGiecj:JW3979
eco:b4019
PATRICifig|511145.12.peg.4132

Organism-specific databases

EchoBASEiEB0582
EcoGeneiEG10587 metH

Phylogenomic databases

eggNOGiENOG4105C3R Bacteria
COG0646 LUCA
COG1410 LUCA
HOGENOMiHOG000251409
InParanoidiP13009
KOiK00548
PhylomeDBiP13009

Enzyme and pathway databases

UniPathwayi
UPA00051;UER00081

BioCyciEcoCyc:HOMOCYSMETB12-MONOMER
MetaCyc:HOMOCYSMETB12-MONOMER
BRENDAi2.1.1.13 2026

Miscellaneous databases

EvolutionaryTraceiP13009
PROiPR:P13009

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
ProtoNetiSearch...

Entry informationi

Entry nameiMETH_ECOLI
AccessioniPrimary (citable) accession number: P13009
Secondary accession number(s): Q2M6T5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 186 of the entry and version 5 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again