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O33259 (METH_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:Rv2124c
ORF Names:MTCY261.20c
OrganismMycobacterium tuberculosis (strain ATCC 25618 / H37Rv) [Reference proteome] [HAMAP]
Taxonomic identifier83332 [NCBI]
Taxonomic lineageBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex

Protein attributes

Sequence length1192 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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.

Was identified as a high-confidence drug target.

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 annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11921192Methionine synthase
PRO_0000204534

Regions

Domain1 – 312312Hcy-binding
Domain343 – 601259Pterin-binding
Domain635 – 72894B12-binding N-terminal
Domain729 – 866138B12-binding
Domain893 – 1192300AdoMet activation
Region819 – 8202Cobalamin-binding By similarity
Region1189 – 11902S-adenosyl-L-methionine binding By similarity

Sites

Metal binding2311Zinc By similarity
Metal binding2971Zinc By similarity
Metal binding2981Zinc By similarity
Metal binding7421Cobalt (cobalamin axial ligand) By similarity
Binding site7871Cobalamin By similarity
Binding site9401S-adenosyl-L-methionine By similarity
Binding site11351S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site11391Cobalamin; via carbonyl oxygen By similarity

Sequences

Sequence LengthMass (Da)Tools
O33259 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 820450DCE77BE15B

FASTA1,192130,323
        10         20         30         40         50         60 
MTAADKHLYD TDLLDVLSQR VMVGDGAMGT QLQAADLTLD DFRGLEGCNE ILNETRPDVL 

        70         80         90        100        110        120 
ETIHRNYFEA GADAVETNTF GCNLSNLGDY DIADRIRDLS QKGTAIARRV ADELGSPDRK 

       130        140        150        160        170        180 
RYVLGSMGPG TKLPTLGHTE YAVIRDAYTE AALGMLDGGA DAILVETCQD LLQLKAAVLG 

       190        200        210        220        230        240 
SRRAMTRAGR HIPVFAHVTV ETTGTMLLGS EIGAALTAVE PLGVDMIGLN CATGPAEMSE 

       250        260        270        280        290        300 
HLRHLSRHAR IPVSVMPNAG LPVLGAKGAE YPLLPDELAE ALAGFIAEFG LSLVGGCCGT 

       310        320        330        340        350        360 
TPAHIREVAA AVANIKRPER QVSYEPSVSS LYTAIPFAQD ASVLVIGERT NANGSKGFRE 

       370        380        390        400        410        420 
AMIAEDYQKC LDIAKDQTRD GAHLLDLCVD YVGRDGVADM KALASRLATS STLPIMLDST 

       430        440        450        460        470        480 
ETAVLQAGLE HLGGRCAINS VNYEDGDGPE SRFAKTMALV AEHGAAVVAL TIDEEGQART 

       490        500        510        520        530        540 
AQKKVEIAER LINDITGNWG VDESSILIDT LTFTIATGQE ESRRDGIETI EAIRELKKRH 

       550        560        570        580        590        600 
PDVQTTLGLS NISFGLNPAA RQVLNSVFLH ECQEAGLDSA IVHASKILPM NRIPEEQRNV 

       610        620        630        640        650        660 
ALDLVYDRRR EDYDPLQELM RLFEGVSAAS SKEDRLAELA GLPLFERLAQ RIVDGERNGL 

       670        680        690        700        710        720 
DADLDEAMTQ KPPLQIINEH LLAGMKTVGE LFGSGQMQLP FVLQSAEVMK AAVAYLEPHM 

       730        740        750        760        770        780 
ERSDDDSGKG RIVLATVKGD VHDIGKNLVD IILSNNGYEV VNIGIKQPIA TILEVAEDKS 

       790        800        810        820        830        840 
ADVVGMSGLL VKSTVVMKEN LEEMNTRGVA EKFPVLLGGA ALTRSYVEND LAEIYQGEVH 

       850        860        870        880        890        900 
YARDAFEGLK LMDTIMSAKR GEAPDENSPE AIKAREKEAE RKARHQRSKR IAAQRKAAEE 

       910        920        930        940        950        960 
PVEVPERSDV AADIEVPAPP FWGSRIVKGL AVADYTGLLD ERALFLGQWG LRGQRGGEGP 

       970        980        990       1000       1010       1020 
SYEDLVETEG RPRLRYWLDR LSTDGILAHA AVVYGYFPAV SEGNDIVVLT EPKPDAPVRY 

      1030       1040       1050       1060       1070       1080 
RFHFPRQQRG RFLCIADFIR SRELAAERGE VDVLPFQLVT MGQPIADFAN ELFASNAYRD 

      1090       1100       1110       1120       1130       1140 
YLEVHGIGVQ LTEALAEYWH RRIREELKFS GDRAMAAEDP EAKEDYFKLG YRGARFAFGY 

      1150       1160       1170       1180       1190 
GACPDLEDRA KMMALLEPER IGVTLSEELQ LHPEQSTDAF VLHHPEAKYF NV 

« Hide

References

[1]"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence."
Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. expand/collapse author list , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G.
Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 25618 / H37Rv.
[2]"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis."
Raman K., Yeturu K., Chandra N.
BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[3]"Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry."
Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M., Kumar P. expand/collapse author list , Chaerkady R., Ramachandran S., Dash D., Pandey A.
Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL123456 Genomic DNA. Translation: CCP44899.1.
PIRG70513.
RefSeqNP_216640.1. NC_000962.3.
YP_006515540.1. NC_018143.2.

3D structure databases

ProteinModelPortalO33259.
SMRO33259. Positions 16-621, 637-1192.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING83332.Rv2124c.

Proteomic databases

PRIDEO33259.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaCCP44899; CCP44899; Rv2124c.
GeneID888711.
KEGGmtu:Rv2124c.
mtv:RVBD_2124c.
PATRIC18153284. VBIMycTub87468_2371.

Organism-specific databases

TubercuListRv2124c.

Phylogenomic databases

eggNOGCOG1410.
HOGENOMHOG000251408.
KOK00548.
OMALTEHYAM.
OrthoDBEOG6091CH.
PhylomeDBO33259.

Enzyme and pathway databases

BioCycMTBRV:RV2124C-MONOMER.
UniPathwayUPA00051; UER00081.

Family and domain databases

Gene3D1.10.1240.10. 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.
InterProIPR003759. 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]
PfamPF02310. 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]
PIRSFPIRSF000381. MetH. 1 hit.
SMARTSM01018. B12-binding_2. 1 hit.
[Graphical view]
SUPFAMSSF47644. SSF47644. 1 hit.
SSF51717. SSF51717. 1 hit.
SSF52242. SSF52242. 1 hit.
SSF56507. SSF56507. 1 hit.
SSF82282. SSF82282. 1 hit.
TIGRFAMsTIGR02082. metH. 1 hit.
PROSITEPS50974. 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]
ProtoNetSearch...

Entry information

Entry nameMETH_MYCTU
AccessionPrimary (citable) accession number: O33259
Secondary accession number(s): L0T8Q3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names