P37586 (METH_SALTY) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	metH
Ordered Locus Names:	STM4188

Organism

Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) [Reference proteome] [HAMAP]

Taxonomic identifier

99287 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Salmonella › Salmonella choleraesuis › Salmonella enterica I › Salmonella typhimurium

Protein attributes

Sequence length	1227 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

General annotation (Comments)

Function	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 By similarity.
Catalytic activity	5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.
Cofactor	Methylcobalamin (MeCBL) By similarity. Binds 1 zinc ion per subunit By similarity.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
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.
Miscellaneous	L-homocysteine is bound via the zinc atom By similarity.
Sequence similarities	Belongs to the vitamin-B12 dependent methionine synthase family. Contains 1 AdoMet activation domain. Contains 1 B12-binding domain. Contains 1 B12-binding N-terminal domain. Contains 1 Hcy-binding domain. Contains 1 pterin-binding domain.
Sequence caution	The sequence AAL23012.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Methionine biosynthesis
Domain	Repeat
Ligand	Cobalamin Cobalt Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	pteridine-containing compound metabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular_function	cobalamin binding Inferred from electronic annotation. Source: UniProtKB-KW homocysteine S-methyltransferase activity Inferred from electronic annotation. Source: InterPro methionine synthase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1227	1226	Methionine synthase		PRO_0000204536
Regions
	Domain	2 – 325	324	Hcy-binding
	Domain	356 – 617	262	Pterin-binding
	Domain	650 – 744	95	B12-binding N-terminal
	Domain	746 – 881	136	B12-binding
	Domain	897 – 1227	331	AdoMet activation
	Region	834 – 835	2	Cobalamin-binding By similarity
	Region	1189 – 1190	2	S-adenosyl-L-methionine binding By similarity
Sites
	Metal binding	247	1	Zinc By similarity
	Metal binding	310	1	Zinc By similarity
	Metal binding	311	1	Zinc By similarity
	Metal binding	759	1	Cobalt (cobalamin axial ligand) By similarity
	Binding site	804	1	Cobalamin By similarity
	Binding site	946	1	S-adenosyl-L-methionine By similarity
	Binding site	1134	1	S-adenosyl-L-methionine; via carbonyl oxygen By similarity
	Binding site	1138	1	Cobalamin; via carbonyl oxygen By similarity
Experimental info
	Sequence conflict	115	1	A → R Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P37586 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 11C8E21745FF5354	FASTA	1,227	136,004
	10 20 30 40 50 60 MSSKVEQLRA QLNERILVLD GGMGTMIQSY RLHEEDFRGE RFADWPCDLK GNNDLLVLSK 70 80 90 100 110 120 PEVIAAIHNA YFEAGADIIE TNTFNSTTIA MADYRMESLS AEINYAAAKL ARACADEWTA 130 140 150 160 170 180 RTPEKPRFVA GVLGPTNRTA SISPDVNDPA FRNITFDQLV AAYRESTKAL VEGGADLILI 190 200 210 220 230 240 ETVFDTLNAK AAVFAVKEEF EALGVDLPIM ISGTITDASG RTLSGQTTEA FYNSLRHAEA 250 260 270 280 290 300 LTFGLNCALG PDELRQYVQE LSRIAECYVT AHPNAGLPNA FGEYDLDADT MAKQIREWAE 310 320 330 340 350 360 AGFLNIVGGC CGTTPEHIAA MSRAVAGLLP RQLPDIPVAC RLSGLEPLNI GDDSLFVNVG 370 380 390 400 410 420 ERTNVTGSAK FKRLIKEEKY SEALDVARQQ VESGAQIIDI NMDEGMLDAE AAMVRFLSLI 430 440 450 460 470 480 AGEPDIARVP IMIDSSKWEV IEKGLKCIQG KGIVNSISMK EGVEAFIHHA KLLRRYGAAV 490 500 510 520 530 540 VVMAFDEQGQ ADTRARKIEI CRRAYKILTE EVGFPPEDII FDPNIFAVAT GIEEHNNYAQ 550 560 570 580 590 600 DFIGACEDIK RELPHALISG GVSNVSFSFR GNDPVREAIH AVFLYYAIRN GMDMGIVNAG 610 620 630 640 650 660 QLAIYDDLPA ELRDAVEDVI LNRRDDGTER LLDLAEKYRG SKTDEAANAQ QAEWRSWDVK 670 680 690 700 710 720 KRLEYSLVKG ITEFIEQDTE EARQQAARPI EVIEGPLMDG MNVVGDLFGE GKMFLPQVVK 730 740 750 760 770 780 SARVMKQAVA YLEPFIEASK EKGSSNGKMV IATVKGDVHD IGKNIVGVVL QCNNYEIVDL 790 800 810 820 830 840 GVMVPAEKIL RTAREVNADL IGLSGLITPS LDEMVNVAKE MERQGFTIPL LIGGATTSKA 850 860 870 880 890 900 HTAVKIEQNY SGPTVYVQNA SRTVGVVAAL LSDTQRDDFV ARTRKEYETV RIQHARKKPR 910 920 930 940 950 960 TPPVTLEAAR DNDLAFDWER YTPPVAHRLG VQEVEASIET LRNYIDWTPF FMTWSLAGKY 970 980 990 1000 1010 1020 PRILEDEVVG VEAQRLFKDA NDMLDKLSAE KLLNPRGVVG LFPANRVGDD IEIYRDETRT 1030 1040 1050 1060 1070 1080 HVLTVSHHLR QQTEKVGFAN YCLADFVAPK LSGKADYIGA FAVTGGLEED ALADAFEAQH 1090 1100 1110 1120 1130 1140 DDYNKIMVKA IADRLAEAFA EYLHERVRKV YWGYAPNESL SNDELIRENY QGIRPAPGYP 1150 1160 1170 1180 1190 1200 ACPEHTEKGT IWQLLDVEKH TGMKLTESFA MWPGASVSGW YFSHPESKYF AVAQIQRDQV 1210 1220 TDYAFRKGMS VEDVERWLAP NLGYDAD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete genome sequence of Salmonella enterica serovar Typhimurium LT2." McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P., Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D., Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E. , Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R., Wilson R.K. Nature 413:852-856(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: LT2 / SGSC1412 / ATCC 700720.
[2]	"The control region of the metH gene of Salmonella typhimurium LT2: an atypical met promoter." Urbanowski M.L., Stauffer G.V. Gene 73:193-200(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-371. Strain: LT2.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE006468 Genomic DNA. Translation: AAL23012.1. Different initiation.
RefSeq	NP_463053.2. NC_003197.1.
3D structure databases
ProteinModelPortal	P37586.
SMR	P37586. Positions 651-1227.
ModBase	Search...
Protein-protein interaction databases
STRING	99287.STM4188.S.
Proteomic databases
PaxDb	P37586.
PRIDE	P37586.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAL23012; AAL23012; STM4188.
GeneID	1255714.
KEGG	stm:STM4188.S.
PATRIC	32387269. VBISalEnt20916_4402.
Phylogenomic databases
eggNOG	COG1410.
KO	K00548.
OMA	VRKEFWG.
ProtClustDB	PRK09490.
Enzyme and pathway databases
BioCyc	SENT99287:GCTI-4218-MONOMER.
UniPathway	UPA00051; UER00081.
Family and domain databases
Gene3D	1.10.1240.10. 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.
InterPro	IPR003759. Cbl-bd_cap. IPR006158. Cobalamin-bd. IPR011005. Dihydropteroate_synth-like. IPR011822. MetH. IPR000489. Pterin-binding. IPR003726. S_MeTrfase. IPR004223. VitB12-dep_Met_synth_activ_dom. [Graphical view]
PANTHER	PTHR21091:SF9. PTHR21091:SF9. 1 hit.
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. [Graphical view]
PIRSF	PIRSF000381. MetH. 1 hit.
SMART	SM01018. B12-binding_2. 1 hit. [Graphical view]
SUPFAM	SSF52242. Cbl-bd. 1 hit. SSF51717. DHP_synth_like. 1 hit. SSF56507. Met_synth_B12. 1 hit. SSF47644. Met_synth_Cbl-bd. 1 hit. SSF82282. S_methyl_trans. 1 hit.
TIGRFAMs	TIGR02082. metH. 1 hit.
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. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

METH_SALTY

Accession

Primary (citable) accession number: P37586

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program