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Protein

Methionine synthase

Gene

Mtr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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

Catalytic activityi

5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.

Cofactori

Protein has several cofactor binding sites:

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi248 – 2481ZincPROSITE-ProRule annotation
Metal bindingi311 – 3111ZincPROSITE-ProRule annotation
Metal bindingi312 – 3121ZincPROSITE-ProRule annotation
Metal bindingi773 – 7731Cobalt (cobalamin axial ligand)By similarity
Binding sitei818 – 8181CobalaminBy similarity
Binding sitei962 – 9621S-adenosyl-L-methionineBy similarity
Binding sitei1160 – 11601S-adenosyl-L-methionine; via carbonyl oxygenBy similarity
Binding sitei1164 – 11641Cobalamin; via carbonyl oxygenBy similarity

GO - Molecular functioni

  1. cobalamin binding Source: UniProtKB-KW
  2. methionine synthase activity Source: MGI
  3. S-adenosylmethionine-homocysteine S-methyltransferase activity Source: InterPro
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. methionine biosynthetic process Source: MGI
  2. pteridine-containing compound metabolic process Source: InterPro
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

ReactomeiREACT_189091. Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE.
REACT_189092. Defective MTR causes methylmalonic aciduria and homocystinuria type cblG.
REACT_189118. Cobalamin (Cbl, vitamin B12) transport and metabolism.
REACT_202492. Sulfur amino acid metabolism.
REACT_241023. Methylation.
UniPathwayiUPA00051; 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 13

Organism-specific databases

MGIiMGI:894292. Mtr.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cytosol Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12531253Methionine synthasePRO_0000312901Add
BLAST

Proteomic databases

MaxQBiA6H5Y3.
PaxDbiA6H5Y3.
PRIDEiA6H5Y3.

PTM databases

PhosphoSiteiA6H5Y3.

Expressioni

Gene expression databases

BgeeiA6H5Y3.
GenevestigatoriA6H5Y3.

Structurei

3D structure databases

ProteinModelPortaliA6H5Y3.
SMRiA6H5Y3. Positions 8-639, 653-908, 914-1252.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 326321Hcy-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini359 – 620262Pterin-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini650 – 74798B12-binding N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini760 – 895136B12-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini911 – 1253343AdoMet activationPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni848 – 8492Cobalamin-bindingBy similarity
Regioni1215 – 12162S-adenosyl-L-methionine bindingBy similarity

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

Contains 1 AdoMet activation domain.PROSITE-ProRule annotation
Contains 1 B12-binding 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

eggNOGiCOG1410.
GeneTreeiENSGT00420000029824.
HOGENOMiHOG000251409.
HOVERGENiHBG006347.
InParanoidiA6H5Y3.
KOiK00548.
OMAiQPFFNAW.
OrthoDBiEOG7TF786.
PhylomeDBiA6H5Y3.
TreeFamiTF312829.

Family and domain databases

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.
IPR011822. MetH.
IPR000489. Pterin-binding.
IPR003726. S_MeTrfase.
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.

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti343 – 3431M → L in BAE24997. (PubMed:16141072)Curated

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.

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. Positions 8-639, 653-908, 914-1252.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

ChEMBLiCHEMBL3188.

PTM databases

PhosphoSiteiA6H5Y3.

Proteomic databases

MaxQBiA6H5Y3.
PaxDbiA6H5Y3.
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

eggNOGiCOG1410.
GeneTreeiENSGT00420000029824.
HOGENOMiHOG000251409.
HOVERGENiHBG006347.
InParanoidiA6H5Y3.
KOiK00548.
OMAiQPFFNAW.
OrthoDBiEOG7TF786.
PhylomeDBiA6H5Y3.
TreeFamiTF312829.

Enzyme and pathway databases

UniPathwayiUPA00051; UER00081.
ReactomeiREACT_189091. Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE.
REACT_189092. Defective MTR causes methylmalonic aciduria and homocystinuria type cblG.
REACT_189118. Cobalamin (Cbl, vitamin B12) transport and metabolism.
REACT_202492. Sulfur amino acid metabolism.
REACT_241023. Methylation.

Miscellaneous databases

NextBioi383806.
PROiA6H5Y3.
SOURCEiSearch...

Gene expression databases

BgeeiA6H5Y3.
GenevestigatoriA6H5Y3.

Family and domain databases

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.
IPR011822. MetH.
IPR000489. Pterin-binding.
IPR003726. S_MeTrfase.
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...

Publicationsi

  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-738.
    Strain: C57BL/6J.
    Tissue: Heart.

Entry informationi

Entry nameiMETH_MOUSE
AccessioniPrimary (citable) accession number: A6H5Y3
Secondary accession number(s): Q3UQP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: July 24, 2007
Last modified: February 4, 2015
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.