UniProtKB - Q4JIJ3 (METH_BOVIN)
Protein
Methionine synthase
Gene
MTR
Organism
Bos taurus (Bovine)
Status
Functioni
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol. MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine.By similarity
Miscellaneous
L-homocysteine is bound via the zinc atom.By similarity
Catalytic activityi
- (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionineEC:2.1.1.13This reaction proceeds in the forwardCurated direction.
Cofactori
Protein has several cofactor binding sites:- methylcob(III)alaminBy similarity
- Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
: L-methionine biosynthesis via de novo pathway Pathwayi
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:
- Methionine synthase (MTR), Methionine synthase (MTR), Methionine synthase (MTR), Methionine synthase (MTR)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 260 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 323 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 324 | ZincPROSITE-ProRule annotation | 1 | |
Binding sitei | 449 | SubstrateBy similarity | 1 | |
Binding sitei | 470 | SubstrateBy similarity | 1 | |
Binding sitei | 537 | SubstrateBy similarity | 1 | |
Binding sitei | 579 | SubstrateBy similarity | 1 | |
Binding sitei | 585 | SubstrateBy similarity | 1 | |
Binding sitei | 591 | SubstrateBy similarity | 1 | |
Metal bindingi | 785 | Cobalt (cobalamin axial ligand)By similarity | 1 | |
Binding sitei | 830 | CobalaminBy similarity | 1 | |
Binding sitei | 974 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 1172 | S-adenosyl-L-methionine; via carbonyl oxygenBy similarity | 1 | |
Binding sitei | 1176 | Cobalamin; via carbonyl oxygenBy similarity | 1 |
GO - Molecular functioni
- cobalamin binding Source: UniProtKB-KW
- methionine synthase activity Source: UniProtKB-EC
- zinc ion binding Source: InterPro
GO - Biological processi
- methylation Source: UniProtKB-KW
- pteridine-containing compound metabolic process Source: InterPro
Keywordsi
Molecular function | Methyltransferase, Transferase |
Biological process | Amino-acid biosynthesis, Methionine biosynthesis |
Ligand | Cobalamin, Cobalt, Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
UniPathwayi | UPA00051;UER00081 |
Names & Taxonomyi
Protein namesi | Recommended name: Methionine synthase (EC:2.1.1.13)Short name: MS Alternative name(s): 5-methyltetrahydrofolate--homocysteine methyltransferase Cobalamin-dependent methionine synthase Vitamin-B12 dependent methionine synthase |
Gene namesi | Name:MTR |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Keywords - Cellular componenti
CytoplasmPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000251734 | 1 – 1265 | Methionine synthaseAdd BLAST | 1265 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1264 | PhosphothreonineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q4JIJ3 |
PRIDEi | Q4JIJ3 |
Interactioni
Subunit structurei
Monomer. Dimer.
Forms a multiprotein complex with MMACHC, MMADHC AND MTRR.
By similarityProtein-protein interaction databases
STRINGi | 9913.ENSBTAP00000016262 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 19 – 338 | Hcy-bindingPROSITE-ProRule annotationAdd BLAST | 320 | |
Domaini | 371 – 632 | Pterin-bindingPROSITE-ProRule annotationAdd BLAST | 262 | |
Domaini | 662 – 759 | B12-binding N-terminalPROSITE-ProRule annotationAdd BLAST | 98 | |
Domaini | 772 – 907 | B12-bindingPROSITE-ProRule annotationAdd BLAST | 136 | |
Domaini | 923 – 1265 | AdoMet activationPROSITE-ProRule annotationAdd BLAST | 343 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 382 – 384 | Substrate bindingBy similarity | 3 | |
Regioni | 860 – 861 | Cobalamin-bindingBy similarity | 2 | |
Regioni | 1227 – 1228 | S-adenosyl-L-methionine bindingBy similarity | 2 |
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
Belongs to the vitamin-B12 dependent methionine synthase family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG1579, Eukaryota |
InParanoidi | Q4JIJ3 |
OrthoDBi | 731388at2759 |
Family and domain databases
CDDi | cd02069, methionine_synthase_B12_BD, 1 hit |
Gene3Di | 1.10.1240.10, 1 hit 3.10.196.10, 1 hit 3.20.20.20, 1 hit 3.20.20.330, 1 hit |
InterProi | View 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 |
Pfami | View 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 |
PIRSFi | PIRSF000381, MetH, 1 hit |
SMARTi | View protein in SMART SM01018, B12-binding_2, 1 hit |
SUPFAMi | SSF47644, SSF47644, 1 hit SSF51717, SSF51717, 1 hit SSF52242, SSF52242, 1 hit SSF56507, SSF56507, 1 hit SSF82282, SSF82282, 1 hit |
TIGRFAMsi | TIGR02082, metH, 1 hit |
PROSITEi | View 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 |
i Sequence
Sequence statusi: Complete.
Q4JIJ3-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAPTLQDLTP SAGMKKTLQD EIEAILQERI MVLDGGMGTM IQRHKLSEED
60 70 80 90 100
FRGQEFKDHA RPLKGNNDIL SITQPNVIYQ IHKEYLLAGA DIIETNTFSS
110 120 130 140 150
TSIAQADYGL EHLAYRMNMC SAGVARKAAE DISLQTGIKR YVAGALGPTN
160 170 180 190 200
KTLSVSPSVE RPDYRNITFD ELVEAYKEQA KGLLDGGVDI LLIETIFDTA
210 220 230 240 250
NAKAALFAVQ KLFEEEYVPR PVFISGTIVD KSGRTLSGQT GEAFVISVSH
260 270 280 290 300
ADPLCIGLNC ALGAAEMRPF IETIGKCTTA YVLCYPNAGL PNTFGDYDET
310 320 330 340 350
PHVMAMHLKD FAVDGLVNIV GGCCGTTPDH IREIAEAVKN CKPRVPPATV
360 370 380 390 400
FEGHMLLSGL EPFRIGPYTN FVNIGERCNV AGSRRFAKLI MAGNYEEALS
410 420 430 440 450
VAKMQVEMGA QVLDINMDDG MLDGPSAMTR FCNFIASEPD IAKVPLCIDS
460 470 480 490 500
SNFAVIEAGL KCCQGKCIVN SISLKEGEDD FLEKARKIKK FGAAVVVMAF
510 520 530 540 550
DEEGQATETD PKIRVCTRAY HLLLKKLGFN PNDIIFDPNI LTIGTGMEEH
560 570 580 590 600
NLYAVNFINA TKVIKETLPG AKVSGGLSNL SFSFRGMEAI REAMHGVFLY
610 620 630 640 650
HAIKFGMDMG IVNAGSLPVY DDIHKELLQL CEDLIWNRDP EATEKLLHYA
660 670 680 690 700
QTQGKGGKKV IQTDEWRNGP LEERLEYALV KGIEKYIIED TEEARLNQEK
710 720 730 740 750
YPRPLNIIEG PLMNGMKIVG DLFGAGKMFL PQVIKSARVM KKAVGHLIPF
760 770 780 790 800
MEKEREETKV LTGKIEDEDP YQGTIVLATV KGDVHDIGKN IVGVVLGCNN
810 820 830 840 850
FRVIDLGVMT PCDKILKAAL DHKADIIGLS GLITPSLDEM IFVAKEMERL
860 870 880 890 900
AIKIPLLIGG ATTSRTHTAV KIAPRYSAPV IHVLDASKSV VVCSQLLDEN
910 920 930 940 950
LKDEYFEEIL EEYEDIRQDH YESLKERRYL TLRQARENGF HIDWLSEPPP
960 970 980 990 1000
VKPTFLGTRV FEDYDLQKLV DYIDWKPFFD VWQLRGKYPN RGFPKIFDDK
1010 1020 1030 1040 1050
TVGEEAKKVY DDAQNMLQAL ISQKKLQARG VVGFWPAQSI QDDIHLYAEG
1060 1070 1080 1090 1100
AVPQASEPIA TFYGLRQQAE KDSASSDPYL CLSDFIAPLH SGIPDYLGLF
1110 1120 1130 1140 1150
AVACFGVEEL SKAYEEECDD YSSIMVKALG DRLAEAFAEE LHERARRELW
1160 1170 1180 1190 1200
GYCSGEQLAV ADLRRLRYEG IRPAPGYPSQ PDHTEKLTVW RLADVEQRTG
1210 1220 1230 1240 1250
IRLTESLAMA PASAVSGLYF SNLKSKYFAV GKISKDQIED YASRKNMSVA
1260
EVEKWLGPIL GYDTD
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | DQ084519 mRNA Translation: AAY86762.1 |
RefSeqi | NP_001025469.1, NM_001030298.1 |
Genome annotation databases
GeneIDi | 280869 |
KEGGi | bta:280869 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | DQ084519 mRNA Translation: AAY86762.1 |
RefSeqi | NP_001025469.1, NM_001030298.1 |
3D structure databases
SMRi | Q4JIJ3 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000016262 |
Proteomic databases
PaxDbi | Q4JIJ3 |
PRIDEi | Q4JIJ3 |
Genome annotation databases
GeneIDi | 280869 |
KEGGi | bta:280869 |
Organism-specific databases
CTDi | 4548 |
Phylogenomic databases
eggNOGi | KOG1579, Eukaryota |
InParanoidi | Q4JIJ3 |
OrthoDBi | 731388at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00051;UER00081 |
Family and domain databases
CDDi | cd02069, methionine_synthase_B12_BD, 1 hit |
Gene3Di | 1.10.1240.10, 1 hit 3.10.196.10, 1 hit 3.20.20.20, 1 hit 3.20.20.330, 1 hit |
InterProi | View 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 |
Pfami | View 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 |
PIRSFi | PIRSF000381, MetH, 1 hit |
SMARTi | View protein in SMART SM01018, B12-binding_2, 1 hit |
SUPFAMi | SSF47644, SSF47644, 1 hit SSF51717, SSF51717, 1 hit SSF52242, SSF52242, 1 hit SSF56507, SSF56507, 1 hit SSF82282, SSF82282, 1 hit |
TIGRFAMsi | TIGR02082, metH, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | METH_BOVIN | |
Accessioni | Q4JIJ3Primary (citable) accession number: Q4JIJ3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 3, 2006 |
Last sequence update: | August 2, 2005 | |
Last modified: | December 2, 2020 | |
This is version 99 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families