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Protein

Methionine synthase

Gene

Mtr

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Miscellaneous

L-homocysteine is bound via the zinc atom.By similarity

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 (Mtr)
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 bindingi248ZincPROSITE-ProRule annotation1
Metal bindingi311ZincPROSITE-ProRule annotation1
Metal bindingi312ZincPROSITE-ProRule annotation1
Binding sitei437SubstrateBy similarity1
Binding sitei458SubstrateBy similarity1
Binding sitei525SubstrateBy similarity1
Binding sitei567SubstrateBy similarity1
Binding sitei573SubstrateBy similarity1
Binding sitei579SubstrateBy similarity1
Metal bindingi773Cobalt (cobalamin axial ligand)By similarity1
Binding sitei818CobalaminBy similarity1
Binding sitei962S-adenosyl-L-methionineBy similarity1
Binding sitei1160S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei1164Cobalamin; via carbonyl oxygenBy similarity1

GO - Molecular functioni

  • amino acid binding Source: MGI
  • cobalamin binding Source: UniProtKB-KW
  • folic acid binding Source: MGI
  • methionine synthase activity Source: MGI
  • methyltransferase activity Source: MGI
  • zinc ion binding Source: InterPro

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

ReactomeiR-MMU-156581 Methylation
R-MMU-1614635 Sulfur amino acid metabolism
R-MMU-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
UniPathwayi
UPA00051;UER00081

Names & Taxonomyi

Protein namesi
Recommended name:
Methionine synthase (EC:2.1.1.13)
Alternative name(s):
5-methyltetrahydrofolate--homocysteine methyltransferase
Vitamin-B12 dependent methionine synthase
Short name:
MS
Gene namesi
Name:Mtr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:894292 Mtr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3188

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003129011 – 1253Methionine synthaseAdd BLAST1253

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1252PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiA6H5Y3
MaxQBiA6H5Y3
PaxDbiA6H5Y3
PeptideAtlasiA6H5Y3
PRIDEiA6H5Y3

PTM databases

iPTMnetiA6H5Y3
PhosphoSitePlusiA6H5Y3

Expressioni

Gene expression databases

BgeeiENSMUSG00000021311 Expressed in 176 organ(s), highest expression level in retina
ExpressionAtlasiA6H5Y3 baseline and differential
GenevisibleiA6H5Y3 MM

Interactioni

Subunit structurei

Monomer. Dimer. Mainly monomer. Interacts with MTRR.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097442

Structurei

3D structure databases

ProteinModelPortaliA6H5Y3
SMRiA6H5Y3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 326Hcy-bindingPROSITE-ProRule annotationAdd BLAST321
Domaini359 – 620Pterin-bindingPROSITE-ProRule annotationAdd BLAST262
Domaini650 – 747B12-binding N-terminalPROSITE-ProRule annotationAdd BLAST98
Domaini760 – 895B12-bindingPROSITE-ProRule annotationAdd BLAST136
Domaini911 – 1253AdoMet activationPROSITE-ProRule annotationAdd BLAST343

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni370 – 372Substrate bindingBy similarity3
Regioni848 – 849Cobalamin-bindingBy similarity2
Regioni1215 – 1216S-adenosyl-L-methionine bindingBy similarity2

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 (By similarity).By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1579 Eukaryota
COG0646 LUCA
COG1410 LUCA
GeneTreeiENSGT00420000029824
HOGENOMiHOG000251409
HOVERGENiHBG006347
InParanoidiA6H5Y3
KOiK00548
OMAiADCIAMS
OrthoDBiEOG091G00WU
PhylomeDBiA6H5Y3
TreeFamiTF312829

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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

A6H5Y3-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKKTLQDEIE AILRKRIMVL DGGMGTMIQR YKLSEEHFQG QEFKDHSRPL
60 70 80 90 100
KGNNDILSIT QPDIIYQIHK EYLLAGADII ETNTFSSTSI AQADYGLEHL
110 120 130 140 150
AYRMNKCSAD VARKAAEEIT LQTGVKRFVA GALGPTNKTL SVSPSVERPD
160 170 180 190 200
YRNITFDELV DAYQEQAKGL LDGRVDILLI ETIFDTANAK AALFAIQNLF
210 220 230 240 250
EENYAPPRPI FISGTIVDKS GRTLSGQTGE AFVTSVSHSD PLCIGLNCSL
260 270 280 290 300
GAAEMRPFIE TIGKCTTAYV LCYPNAGLPN TFGDYDETPS TMATHLKDFA
310 320 330 340 350
VDGLVNIVGG CCGSTPDHIR EIAEAVKKCK PRVPPASVFE GHMLLSGLEP
360 370 380 390 400
FRIGPYTNFV NIGERCNVAG SRKFAKLIMA GNYEEALSIA KAQVEMGAQV
410 420 430 440 450
LDINMDDGML DGPSAMTRFC NSIASEPDIA KVPLCIDSSN FAVIEAGLKC
460 470 480 490 500
CQGKCIVNSI SLKEGEGDFL EKARKIKKFG AAVVVMAFDE EGQATETDVK
510 520 530 540 550
VNVCTRAYHL LVDKVGFNPN DIIFDPNILT IGTGMEEHNL YAINFIHATR
560 570 580 590 600
VIKETLPGVR ISGGLSNLSF SFRGMEAIRE AMHGVFLYHA IKFGMDMGIV
610 620 630 640 650
NAGNLPVYDA IHKDLLQLCE DLIWNKDSEA TEKLLRYAQT HGTGGKKVIQ
660 670 680 690 700
TDEWRNGSIE ERLEYALVKG IEKHIVEDTE EARLNGEKYP RPLNIIEGPL
710 720 730 740 750
MNGMKVVGDL FGAGKMFLPQ VIKSARVMKK AVGHLIPFME KEREEARLIN
760 770 780 790 800
GSVEEEDPYQ GTIVLATVKG DVHDIGKNIV GVVLACNNFR VIDLGVMTPC
810 820 830 840 850
DKILQAALDH KADIIGLSGL ITPSLDEMIF VAKEMERLAI KIPLLIGGAT
860 870 880 890 900
TSRTHTAVKI APRYSAPVIH VLDASKSVVV CSQLLDENLR DDYFEEILEE
910 920 930 940 950
YEDIRQDHYE SLKERKYVPL SQARKHGFHI DWLSEPHPVK PTFIGTQVFE
960 970 980 990 1000
DYNLQKLVDY IDWKPFFDVW QLRGKYPNRG FPKIFNDKAV GEEARKVYND
1010 1020 1030 1040 1050
AQNMLNILIS QKKLQARGVV GFWPAQSVQD DIHLYAEGVV PQAAEPIATF
1060 1070 1080 1090 1100
YGLRQQAEKD SSSTDPYHCL SDFIAPLHSG VCDYLGLFAV ACFGVEELSK
1110 1120 1130 1140 1150
TYEDDGDDYS SIMVKALGDR LAEAFAEELH ERVRRELWAY SRSEQLGVPD
1160 1170 1180 1190 1200
LRRLRYEGIR PAPGYPSQPD HTEKLTMWRL ASIEQATGIR LTESLAMAPA
1210 1220 1230 1240 1250
SAVSGLYFSN VKAKYFAVGK ISKDQTEDYA LRKNMPVAEV EKWLGPILGY

DTD
Length:1,253
Mass (Da):139,069
Last modified:July 24, 2007 - v1
Checksum:i5507CAD9F9522537
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1Y7VM88A0A1Y7VM88_MOUSE
Methionine synthase
Mtr
222Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti343M → L in BAE24997 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC145683 mRNA Translation: AAI45684.1
BC145685 mRNA Translation: AAI45686.1
AK142258 mRNA Translation: BAE24997.1
CCDSiCCDS36591.1
RefSeqiNP_001074597.1, NM_001081128.3
UniGeneiMm.40335

Genome annotation databases

EnsembliENSMUST00000099856; ENSMUSP00000097442; ENSMUSG00000021311
GeneIDi238505
KEGGimmu:238505
UCSCiuc007plh.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC145683 mRNA Translation: AAI45684.1
BC145685 mRNA Translation: AAI45686.1
AK142258 mRNA Translation: BAE24997.1
CCDSiCCDS36591.1
RefSeqiNP_001074597.1, NM_001081128.3
UniGeneiMm.40335

3D structure databases

ProteinModelPortaliA6H5Y3
SMRiA6H5Y3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097442

Chemistry databases

ChEMBLiCHEMBL3188

PTM databases

iPTMnetiA6H5Y3
PhosphoSitePlusiA6H5Y3

Proteomic databases

EPDiA6H5Y3
MaxQBiA6H5Y3
PaxDbiA6H5Y3
PeptideAtlasiA6H5Y3
PRIDEiA6H5Y3

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000099856; ENSMUSP00000097442; ENSMUSG00000021311
GeneIDi238505
KEGGimmu:238505
UCSCiuc007plh.2 mouse

Organism-specific databases

CTDi4548
MGIiMGI:894292 Mtr

Phylogenomic databases

eggNOGiKOG1579 Eukaryota
COG0646 LUCA
COG1410 LUCA
GeneTreeiENSGT00420000029824
HOGENOMiHOG000251409
HOVERGENiHBG006347
InParanoidiA6H5Y3
KOiK00548
OMAiADCIAMS
OrthoDBiEOG091G00WU
PhylomeDBiA6H5Y3
TreeFamiTF312829

Enzyme and pathway databases

UniPathwayi
UPA00051;UER00081

ReactomeiR-MMU-156581 Methylation
R-MMU-1614635 Sulfur amino acid metabolism
R-MMU-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism

Miscellaneous databases

PROiPR:A6H5Y3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021311 Expressed in 176 organ(s), highest expression level in retina
ExpressionAtlasiA6H5Y3 baseline and differential
GenevisibleiA6H5Y3 MM

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_MOUSE
AccessioniPrimary (citable) accession number: A6H5Y3
Secondary accession number(s): Q3UQP2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: July 24, 2007
Last modified: November 7, 2018
This is version 105 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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