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A6H5Y3 (METH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 71. 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
Vitamin-B12 dependent methionine synthase
Short name=MS
Gene names
Name:Mtr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1253 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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.

Subcellular location

Cytoplasm By similarity.

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 annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12531253Methionine synthase
PRO_0000312901

Regions

Domain6 – 326321Hcy-binding
Domain359 – 620262Pterin-binding
Domain650 – 74798B12-binding N-terminal
Domain760 – 895136B12-binding
Domain911 – 1253343AdoMet activation
Region848 – 8492Cobalamin-binding By similarity
Region1215 – 12162S-adenosyl-L-methionine binding By similarity

Sites

Metal binding2481Zinc By similarity
Metal binding3111Zinc By similarity
Metal binding3121Zinc By similarity
Metal binding7731Cobalt (cobalamin axial ligand) By similarity
Binding site8181Cobalamin By similarity
Binding site9621S-adenosyl-L-methionine By similarity
Binding site11601S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site11641Cobalamin; via carbonyl oxygen By similarity

Experimental info

Sequence conflict3431M → L in BAE24997. Ref.2

Sequences

Sequence LengthMass (Da)Tools
A6H5Y3 [UniParc].

Last modified July 24, 2007. Version 1.
Checksum: 5507CAD9F9522537

FASTA1,253139,069
        10         20         30         40         50         60 
MKKTLQDEIE AILRKRIMVL DGGMGTMIQR YKLSEEHFQG QEFKDHSRPL KGNNDILSIT 

        70         80         90        100        110        120 
QPDIIYQIHK EYLLAGADII ETNTFSSTSI AQADYGLEHL AYRMNKCSAD VARKAAEEIT 

       130        140        150        160        170        180 
LQTGVKRFVA GALGPTNKTL SVSPSVERPD YRNITFDELV DAYQEQAKGL LDGRVDILLI 

       190        200        210        220        230        240 
ETIFDTANAK AALFAIQNLF EENYAPPRPI FISGTIVDKS GRTLSGQTGE AFVTSVSHSD 

       250        260        270        280        290        300 
PLCIGLNCSL GAAEMRPFIE TIGKCTTAYV LCYPNAGLPN TFGDYDETPS TMATHLKDFA 

       310        320        330        340        350        360 
VDGLVNIVGG CCGSTPDHIR EIAEAVKKCK PRVPPASVFE GHMLLSGLEP FRIGPYTNFV 

       370        380        390        400        410        420 
NIGERCNVAG SRKFAKLIMA GNYEEALSIA KAQVEMGAQV LDINMDDGML DGPSAMTRFC 

       430        440        450        460        470        480 
NSIASEPDIA KVPLCIDSSN FAVIEAGLKC CQGKCIVNSI SLKEGEGDFL EKARKIKKFG 

       490        500        510        520        530        540 
AAVVVMAFDE EGQATETDVK VNVCTRAYHL LVDKVGFNPN DIIFDPNILT IGTGMEEHNL 

       550        560        570        580        590        600 
YAINFIHATR VIKETLPGVR ISGGLSNLSF SFRGMEAIRE AMHGVFLYHA IKFGMDMGIV 

       610        620        630        640        650        660 
NAGNLPVYDA IHKDLLQLCE DLIWNKDSEA TEKLLRYAQT HGTGGKKVIQ TDEWRNGSIE 

       670        680        690        700        710        720 
ERLEYALVKG IEKHIVEDTE EARLNGEKYP RPLNIIEGPL MNGMKVVGDL FGAGKMFLPQ 

       730        740        750        760        770        780 
VIKSARVMKK AVGHLIPFME KEREEARLIN GSVEEEDPYQ GTIVLATVKG DVHDIGKNIV 

       790        800        810        820        830        840 
GVVLACNNFR VIDLGVMTPC DKILQAALDH KADIIGLSGL ITPSLDEMIF VAKEMERLAI 

       850        860        870        880        890        900 
KIPLLIGGAT TSRTHTAVKI APRYSAPVIH VLDASKSVVV CSQLLDENLR DDYFEEILEE 

       910        920        930        940        950        960 
YEDIRQDHYE SLKERKYVPL SQARKHGFHI DWLSEPHPVK PTFIGTQVFE DYNLQKLVDY 

       970        980        990       1000       1010       1020 
IDWKPFFDVW QLRGKYPNRG FPKIFNDKAV GEEARKVYND AQNMLNILIS QKKLQARGVV 

      1030       1040       1050       1060       1070       1080 
GFWPAQSVQD DIHLYAEGVV PQAAEPIATF YGLRQQAEKD SSSTDPYHCL SDFIAPLHSG 

      1090       1100       1110       1120       1130       1140 
VCDYLGLFAV ACFGVEELSK TYEDDGDDYS SIMVKALGDR LAEAFAEELH ERVRRELWAY 

      1150       1160       1170       1180       1190       1200 
SRSEQLGVPD LRRLRYEGIR PAPGYPSQPD HTEKLTMWRL ASIEQATGIR LTESLAMAPA 

      1210       1220       1230       1240       1250 
SAVSGLYFSN VKAKYFAVGK ISKDQTEDYA LRKNMPVAEV EKWLGPILGY DTD 

« Hide

References

[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC145683 mRNA. Translation: AAI45684.1.
BC145685 mRNA. Translation: AAI45686.1.
AK142258 mRNA. Translation: BAE24997.1.
CCDSCCDS36591.1.
RefSeqNP_001074597.1. NM_001081128.3.
UniGeneMm.40335.

3D structure databases

ProteinModelPortalA6H5Y3.
SMRA6H5Y3. Positions 4-639, 653-908, 914-1252.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL3188.

PTM databases

PhosphoSiteA6H5Y3.

Proteomic databases

MaxQBA6H5Y3.
PaxDbA6H5Y3.
PRIDEA6H5Y3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000099856; ENSMUSP00000097442; ENSMUSG00000021311.
GeneID238505.
KEGGmmu:238505.
UCSCuc007plh.2. mouse.

Organism-specific databases

CTD4548.
MGIMGI:894292. Mtr.

Phylogenomic databases

eggNOGCOG1410.
GeneTreeENSGT00420000029824.
HOGENOMHOG000251409.
HOVERGENHBG006347.
InParanoidA6H5Y3.
KOK00548.
OMALTEHYAM.
OrthoDBEOG7TF786.
PhylomeDBA6H5Y3.
TreeFamTF312829.

Enzyme and pathway databases

UniPathwayUPA00051; UER00081.

Gene expression databases

BgeeA6H5Y3.
GenevestigatorA6H5Y3.

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...

Other

NextBio383806.
PROA6H5Y3.
SOURCESearch...

Entry information

Entry nameMETH_MOUSE
AccessionPrimary (citable) accession number: A6H5Y3
Secondary accession number(s): Q3UQP2
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: July 24, 2007
Last modified: July 9, 2014
This is version 71 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot