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Protein

Methionine synthase

Gene

metH

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

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
  • S-adenosylmethionine-homocysteine S-methyltransferase activity Source: InterPro
  • zinc ion binding Source: EcoCyc

GO - Biological processi

  • homocysteine metabolic process Source: BHF-UCL
  • methionine biosynthetic process Source: BHF-UCL
  • tetrahydrofolate interconversion Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

Amino-acid biosynthesis, Methionine biosynthesis

Keywords - Ligandi

Cobalamin, Cobalt, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BioCyciEcoCyc:HOMOCYSMETB12-MONOMER.
ECOL316407:JW3979-MONOMER.
MetaCyc:HOMOCYSMETB12-MONOMER.
BRENDAi2.1.1.13. 2026.
UniPathwayiUPA00051; 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

  • cytoplasm Source: EcoliWiki
  • cytosol Source: EcoCyc
Complete GO annotation...

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

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-2DPAGEP13009.

Interactioni

Protein-protein interaction databases

BioGridi4263452. 15 interactors.
IntActiP13009. 13 interactors.
STRINGi511145.b4019.

Structurei

Secondary structure

11227
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi653 – 656Combined sources4
Helixi659 – 669Combined sources11
Helixi675 – 685Combined sources11
Beta strandi686 – 688Combined sources3
Helixi691 – 694Combined sources4
Helixi696 – 710Combined sources15
Helixi715 – 737Combined sources23
Beta strandi738 – 741Combined sources4
Beta strandi748 – 754Combined sources7
Helixi761 – 771Combined sources11
Turni772 – 774Combined sources3
Beta strandi776 – 779Combined sources4
Beta strandi782 – 784Combined sources3
Helixi786 – 796Combined sources11
Beta strandi799 – 804Combined sources6
Helixi809 – 823Combined sources15
Beta strandi830 – 834Combined sources5
Beta strandi835 – 837Combined sources3
Helixi839 – 845Combined sources7
Helixi847 – 849Combined sources3
Beta strandi854 – 856Combined sources3
Helixi860 – 870Combined sources11
Turni873 – 875Combined sources3
Helixi876 – 893Combined sources18
Helixi906 – 911Combined sources6
Helixi918 – 920Combined sources3
Beta strandi930 – 935Combined sources6
Helixi938 – 941Combined sources4
Helixi942 – 944Combined sources3
Helixi948 – 953Combined sources6
Helixi962 – 965Combined sources4
Turni967 – 969Combined sources3
Helixi970 – 990Combined sources21
Beta strandi996 – 1007Combined sources12
Beta strandi1010 – 1016Combined sources7
Beta strandi1022 – 1027Combined sources6
Beta strandi1036 – 1038Combined sources3
Helixi1043 – 1046Combined sources4
Helixi1050 – 1052Combined sources3
Beta strandi1057 – 1065Combined sources9
Helixi1069 – 1078Combined sources10
Helixi1082 – 1109Combined sources28
Helixi1122 – 1126Combined sources5
Beta strandi1130 – 1133Combined sources4
Helixi1145 – 1147Combined sources3
Helixi1148 – 1154Combined sources7
Helixi1157 – 1161Combined sources5
Beta strandi1167 – 1169Combined sources3
Beta strandi1171 – 1182Combined sources12
Helixi1197 – 1207Combined sources11
Helixi1211 – 1218Combined sources8
Helixi1219 – 1221Combined sources3
Beta strandi1222 – 1224Combined sources3

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[»]
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

Contains 1 AdoMet activation domain.PROSITE-ProRule annotation
Contains 1 B12-binding domain.PROSITE-ProRule annotation
Contains 1 B12-binding N-terminal domain.PROSITE-ProRule annotation
Contains 1 Hcy-binding domain.PROSITE-ProRule annotation
Contains 1 pterin-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG4105C3R. Bacteria.
COG0646. LUCA.
COG1410. LUCA.
HOGENOMiHOG000251409.
InParanoidiP13009.
KOiK00548.
OMAiDYNSIMV.
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.
3.40.50.280. 1 hit.
InterProiIPR003759. Cbl-bd_cap.
IPR006158. Cobalamin-bd.
IPR011005. Dihydropteroate_synth-like.
IPR003726. HCY_dom.
IPR033706. Met_synthase_B12-bd.
IPR011822. MetH.
IPR000489. Pterin-binding_dom.
IPR004223. VitB12-dep_Met_synth_activ_dom.
[Graphical view]
PfamiPF02310. 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.
[Graphical view]
PIRSFiPIRSF000381. MetH. 1 hit.
SMARTiSM01018. B12-binding_2. 1 hit.
[Graphical view]
SUPFAMiSSF47644. SSF47644. 1 hit.
SSF51717. SSF51717. 1 hit.
SSF52242. SSF52242. 1 hit.
SSF56507. SSF56507. 1 hit.
SSF82282. SSF82282. 1 hit.
TIGRFAMsiTIGR02082. metH. 1 hit.
PROSITEiPS50974. ADOMET_ACTIVATION. 1 hit.
PS51332. B12_BINDING. 1 hit.
PS51337. B12_BINDING_NTER. 1 hit.
PS50970. HCY. 1 hit.
PS50972. PTERIN_BINDING. 1 hit.
[Graphical view]

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.
PATRICi32123567. VBIEscCol129921_4132.

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[»]
ProteinModelPortaliP13009.
SMRiP13009.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4263452. 15 interactors.
IntActiP13009. 13 interactors.
STRINGi511145.b4019.

2D gel databases

SWISS-2DPAGEP13009.

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.
PATRICi32123567. VBIEscCol129921_4132.

Organism-specific databases

EchoBASEiEB0582.
EcoGeneiEG10587. metH.

Phylogenomic databases

eggNOGiENOG4105C3R. Bacteria.
COG0646. LUCA.
COG1410. LUCA.
HOGENOMiHOG000251409.
InParanoidiP13009.
KOiK00548.
OMAiDYNSIMV.
PhylomeDBiP13009.

Enzyme and pathway databases

UniPathwayiUPA00051; UER00081.
BioCyciEcoCyc:HOMOCYSMETB12-MONOMER.
ECOL316407:JW3979-MONOMER.
MetaCyc:HOMOCYSMETB12-MONOMER.
BRENDAi2.1.1.13. 2026.

Miscellaneous databases

EvolutionaryTraceiP13009.
PROiP13009.

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.
3.40.50.280. 1 hit.
InterProiIPR003759. Cbl-bd_cap.
IPR006158. Cobalamin-bd.
IPR011005. Dihydropteroate_synth-like.
IPR003726. HCY_dom.
IPR033706. Met_synthase_B12-bd.
IPR011822. MetH.
IPR000489. Pterin-binding_dom.
IPR004223. VitB12-dep_Met_synth_activ_dom.
[Graphical view]
PfamiPF02310. 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.
[Graphical view]
PIRSFiPIRSF000381. MetH. 1 hit.
SMARTiSM01018. B12-binding_2. 1 hit.
[Graphical view]
SUPFAMiSSF47644. SSF47644. 1 hit.
SSF51717. SSF51717. 1 hit.
SSF52242. SSF52242. 1 hit.
SSF56507. SSF56507. 1 hit.
SSF82282. SSF82282. 1 hit.
TIGRFAMsiTIGR02082. metH. 1 hit.
PROSITEiPS50974. ADOMET_ACTIVATION. 1 hit.
PS51332. B12_BINDING. 1 hit.
PS51337. B12_BINDING_NTER. 1 hit.
PS50970. HCY. 1 hit.
PS50972. PTERIN_BINDING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMETH_ECOLI
AccessioniPrimary (citable) accession number: P13009
Secondary accession number(s): Q2M6T5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 172 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

L-homocysteine is bound via the zinc atom.

Keywords - Technical termi

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

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.