UniProtKB - P13009 (METH_ECOLI)
Protein
Methionine synthase
Gene
metH
Organism
Escherichia coli (strain K12)
Status
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
- (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionineEC:2.1.1.13
Cofactori
Protein has several cofactor binding sites:- methylcob(III)alamin
- Zn2+Note: Binds 1 zinc ion per subunit.
: L-methionine biosynthesis via de novo pathway Pathwayi
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:
- Methionine synthase (metH), Methionine synthase (metH)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 247 | Zinc | 1 | |
Metal bindingi | 310 | Zinc | 1 | |
Metal bindingi | 311 | Zinc | 1 | |
Binding sitei | 694 | Methylcob(III)alaminCombined sources1 Publication | 1 | |
Metal bindingi | 759 | Cobalt (methylcob(III)alamin axial ligand)Combined sources1 Publication | 1 | |
Binding sitei | 804 | Methylcob(III)alaminCombined sources1 Publication | 1 | |
Binding sitei | 808 | Methylcob(III)alaminCombined sources1 Publication | 1 | |
Binding sitei | 860 | Methylcob(III)alamin; via amide nitrogenCombined sources1 Publication | 1 | |
Binding sitei | 946 | S-adenosyl-L-methionine1 Publication | 1 | |
Binding sitei | 1134 | S-adenosyl-L-methionine; via carbonyl oxygen1 Publication | 1 |
GO - Molecular functioni
- cobalamin binding Source: BHF-UCL
- methionine synthase activity Source: BHF-UCL
- zinc ion binding Source: EcoCyc
GO - Biological processi
- homocysteine metabolic process Source: BHF-UCL
- methionine biosynthetic process Source: BHF-UCL
- methylation Source: UniProtKB-KW
- tetrahydrofolate interconversion Source: BHF-UCL
Keywordsi
Molecular function | Methyltransferase, Transferase |
Biological process | Amino-acid biosynthesis, Methionine biosynthesis |
Ligand | Cobalamin, Cobalt, Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
BioCyci | EcoCyc:HOMOCYSMETB12-MONOMER MetaCyc:HOMOCYSMETB12-MONOMER |
BRENDAi | 2.1.1.13, 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 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 310 | C → A or S: Loss of zinc binding. Loss of catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 311 | C → A or S: Loss of zinc binding. Loss of catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 757 | D → E: Decreases activity by about 70%. 1 Publication | 1 | |
Mutagenesisi | 757 | D → N: Decreases activity by about 45%. 1 Publication | 1 | |
Mutagenesisi | 759 | H → G: Loss of catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 810 | S → A: Decreases activity by about 40%. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000204532 | 2 – 1227 | Methionine synthaseAdd BLAST | 1226 |
Proteomic databases
jPOSTi | P13009 |
PaxDbi | P13009 |
PRIDEi | P13009 |
2D gel databases
SWISS-2DPAGEi | P13009 |
Interactioni
Protein-protein interaction databases
BioGRIDi | 4263452, 39 interactors |
IntActi | P13009, 13 interactors |
STRINGi | 511145.b4019 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P13009 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P13009 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2 – 325 | Hcy-bindingPROSITE-ProRule annotationAdd BLAST | 324 | |
Domaini | 356 – 617 | Pterin-bindingPROSITE-ProRule annotationAdd BLAST | 262 | |
Domaini | 650 – 744 | B12-binding N-terminalPROSITE-ProRule annotationAdd BLAST | 95 | |
Domaini | 746 – 881 | B12-bindingPROSITE-ProRule annotationAdd BLAST | 136 | |
Domaini | 897 – 1227 | AdoMet activationPROSITE-ProRule annotationAdd BLAST | 331 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 756 – 760 | Methylcob(III)alamin bindingCombined sources1 Publication | 5 | |
Regioni | 1189 – 1190 | S-adenosyl-L-methionine binding | 2 |
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
Belongs to the vitamin-B12 dependent methionine synthase family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | COG0646, Bacteria COG1410, Bacteria |
HOGENOMi | CLU_004914_2_0_6 |
InParanoidi | P13009 |
PhylomeDBi | P13009 |
Family and domain databases
CDDi | cd02069, methionine_synthase_B12_BD, 1 hit |
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 |
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 |
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 |
PIRSFi | PIRSF000381, MetH, 1 hit |
SMARTi | View protein in SMART SM01018, B12-binding_2, 1 hit |
SUPFAMi | SSF47644, SSF47644, 1 hit SSF51717, SSF51717, 1 hit SSF52242, SSF52242, 1 hit SSF56507, SSF56507, 1 hit SSF82282, SSF82282, 1 hit |
TIGRFAMsi | TIGR02082, metH, 1 hit |
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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P13009-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 113 | A → R (PubMed:2185137).Curated | 1 | |
Sequence conflicti | 113 | A → R (PubMed:2668277).Curated | 1 | |
Sequence conflicti | 641 | S → T (PubMed:2185137).Curated | 1 | |
Sequence conflicti | 641 | S → T (PubMed:2668277).Curated | 1 | |
Sequence conflicti | 1079 – 1080 | QH → HD in CAA34601 (PubMed:2185137).Curated | 2 | |
Sequence conflicti | 1195 – 1227 | IQRDQ…GYDAD → TSARSG in CAA34601 (PubMed:2185137).CuratedAdd BLAST | 33 |
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 |
PIRi | B65209, XYECMH |
RefSeqi | NP_418443.1, NC_000913.3 WP_000096011.1, NZ_SSZK01000049.1 |
Genome annotation databases
EnsemblBacteriai | AAC76989; AAC76989; b4019 BAE78021; BAE78021; BAE78021 |
GeneIDi | 57730514 948522 |
KEGGi | ecj:JW3979 eco:b4019 |
PATRICi | fig|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 |
PIRi | B65209, XYECMH |
RefSeqi | NP_418443.1, NC_000913.3 WP_000096011.1, NZ_SSZK01000049.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BMT | X-ray | 3.00 | A/B | 651-896 | [»] | |
1K7Y | X-ray | 3.00 | A | 651-1227 | [»] | |
1K98 | X-ray | 3.75 | A | 651-1227 | [»] | |
1MSK | X-ray | 1.80 | A | 897-1227 | [»] | |
3BUL | X-ray | 2.30 | A | 649-1227 | [»] | |
3IV9 | X-ray | 3.25 | A | 649-1227 | [»] | |
3IVA | X-ray | 2.70 | A | 649-1227 | [»] | |
6BDY | X-ray | 1.51 | A | 897-1227 | [»] | |
6BM5 | X-ray | 1.50 | A | 897-1227 | [»] | |
6BM6 | X-ray | 1.50 | A | 897-1227 | [»] | |
SMRi | P13009 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4263452, 39 interactors |
IntActi | P13009, 13 interactors |
STRINGi | 511145.b4019 |
2D gel databases
SWISS-2DPAGEi | P13009 |
Proteomic databases
jPOSTi | P13009 |
PaxDbi | P13009 |
PRIDEi | P13009 |
Genome annotation databases
EnsemblBacteriai | AAC76989; AAC76989; b4019 BAE78021; BAE78021; BAE78021 |
GeneIDi | 57730514 948522 |
KEGGi | ecj:JW3979 eco:b4019 |
PATRICi | fig|511145.12.peg.4132 |
Organism-specific databases
EchoBASEi | EB0582 |
Phylogenomic databases
eggNOGi | COG0646, Bacteria COG1410, Bacteria |
HOGENOMi | CLU_004914_2_0_6 |
InParanoidi | P13009 |
PhylomeDBi | P13009 |
Enzyme and pathway databases
UniPathwayi | UPA00051;UER00081 |
BioCyci | EcoCyc:HOMOCYSMETB12-MONOMER MetaCyc:HOMOCYSMETB12-MONOMER |
BRENDAi | 2.1.1.13, 2026 |
Miscellaneous databases
EvolutionaryTracei | P13009 |
PROi | PR:P13009 |
Family and domain databases
CDDi | cd02069, methionine_synthase_B12_BD, 1 hit |
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 |
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 |
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 |
PIRSFi | PIRSF000381, MetH, 1 hit |
SMARTi | View protein in SMART SM01018, B12-binding_2, 1 hit |
SUPFAMi | SSF47644, SSF47644, 1 hit SSF51717, SSF51717, 1 hit SSF52242, SSF52242, 1 hit SSF56507, SSF56507, 1 hit SSF82282, SSF82282, 1 hit |
TIGRFAMsi | TIGR02082, metH, 1 hit |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | METH_ECOLI | |
Accessioni | P13009Primary (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: | April 7, 2021 | |
This is version 202 of the entry and version 5 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families