ID METH_BOVIN Reviewed; 1265 AA.
AC Q4JIJ3;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 27-MAR-2024, entry version 110.
DE RecName: Full=Methionine synthase;
DE Short=MS;
DE EC=2.1.1.13 {ECO:0000250|UniProtKB:Q9Z2Q4};
DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase;
DE AltName: Full=Cobalamin-dependent methionine synthase;
DE AltName: Full=Vitamin-B12 dependent methionine synthase;
GN Name=MTR;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Palin M.-F., Beaudry D., Charest R., Girard C.;
RT "Interactions of folic acid-vitamin B12-methionine: effects on liver
RT metabolism and production of dairy cows.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the transfer of a methyl group from
CC methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound
CC cob(I)alamin and methionine in the cytosol. MeCbl is an active form of
CC cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis.
CC Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl
CC group from 5-methyltetrahydrofolate. The processing of cobalamin in the
CC cytosol occurs in a multiprotein complex composed of at least MMACHC,
CC MMADHC, MTRR (methionine synthase reductase) and MTR which may
CC contribute to shuttle safely and efficiently cobalamin towards MTR in
CC order to produce methionine. {ECO:0000250|UniProtKB:Q99707}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine =
CC (6S)-5,6,7,8-tetrahydrofolate + L-methionine; Xref=Rhea:RHEA:11172,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57453, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:58199; EC=2.1.1.13;
CC Evidence={ECO:0000250|UniProtKB:Q9Z2Q4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11173;
CC Evidence={ECO:0000250|UniProtKB:Q9Z2Q4};
CC -!- COFACTOR:
CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC Evidence={ECO:0000250|UniProtKB:P13009};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P13009};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P13009};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
CC {ECO:0000250|UniProtKB:Q99707}.
CC -!- SUBUNIT: Monomer. Dimer. Forms a multiprotein complex with MMACHC,
CC MMADHC and MTRR. {ECO:0000250|UniProtKB:Q99707}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99707}.
CC -!- DOMAIN: Modular enzyme with four functionally distinct domains. The
CC isolated Hcy-binding domain catalyzes methyl transfer from free
CC methylcobalamin to homocysteine. The Hcy-binding domain in association
CC with the pterin-binding domain catalyzes the methylation of
CC cob(I)alamin by methyltetrahydrofolate and the methylation of
CC homocysteine. The B12-binding domain binds the cofactor. The AdoMet
CC activation domain binds S-adenosyl-L-methionine. Under aerobic
CC conditions cob(I)alamin can be converted to inactive cob(II)alamin.
CC Reductive methylation by S-adenosyl-L-methionine and flavodoxin
CC regenerates methylcobalamin (By similarity).
CC {ECO:0000250|UniProtKB:P13009}.
CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase
CC family. {ECO:0000305}.
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DR EMBL; DQ084519; AAY86762.1; -; mRNA.
DR RefSeq; NP_001025469.1; NM_001030298.1.
DR AlphaFoldDB; Q4JIJ3; -.
DR SMR; Q4JIJ3; -.
DR STRING; 9913.ENSBTAP00000067894; -.
DR PaxDb; 9913-ENSBTAP00000016262; -.
DR GeneID; 280869; -.
DR KEGG; bta:280869; -.
DR CTD; 4548; -.
DR eggNOG; KOG1579; Eukaryota.
DR InParanoid; Q4JIJ3; -.
DR OrthoDB; 66796at2759; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0008705; F:methionine synthase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0050667; P:homocysteine metabolic process; IBA:GO_Central.
DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0046653; P:tetrahydrofolate metabolic process; IBA:GO_Central.
DR CDD; cd02069; methionine_synthase_B12_BD; 1.
DR CDD; cd00740; MeTr; 1.
DR Gene3D; 3.40.50.280; Cobalamin-binding domain; 1.
DR Gene3D; 1.10.288.10; Cobalamin-dependent Methionine Synthase, domain 2; 1.
DR Gene3D; 3.20.20.20; Dihydropteroate synthase-like; 1.
DR Gene3D; 3.20.20.330; Homocysteine-binding-like domain; 1.
DR Gene3D; 1.10.1240.10; Methionine synthase domain; 1.
DR Gene3D; 3.10.196.10; Vitamin B12-dependent methionine synthase, activation domain; 1.
DR InterPro; IPR003759; Cbl-bd_cap.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR InterPro; IPR011005; Dihydropteroate_synth-like_sf.
DR InterPro; IPR003726; HCY_dom.
DR InterPro; IPR036589; HCY_dom_sf.
DR InterPro; IPR033706; Met_synthase_B12-bd.
DR InterPro; IPR011822; MetH.
DR InterPro; IPR036594; Meth_synthase_dom.
DR InterPro; IPR000489; Pterin-binding_dom.
DR InterPro; IPR004223; VitB12-dep_Met_synth_activ_dom.
DR InterPro; IPR037010; VitB12-dep_Met_synth_activ_sf.
DR NCBIfam; TIGR02082; metH; 1.
DR PANTHER; PTHR45833; METHIONINE SYNTHASE; 1.
DR PANTHER; PTHR45833:SF1; METHIONINE SYNTHASE; 1.
DR Pfam; PF02310; B12-binding; 1.
DR Pfam; PF02607; B12-binding_2; 1.
DR Pfam; PF02965; Met_synt_B12; 1.
DR Pfam; PF00809; Pterin_bind; 1.
DR Pfam; PF02574; S-methyl_trans; 1.
DR PIRSF; PIRSF000381; MetH; 1.
DR SMART; SM01018; B12-binding_2; 1.
DR SUPFAM; SSF52242; Cobalamin (vitamin B12)-binding domain; 1.
DR SUPFAM; SSF51717; Dihydropteroate synthetase-like; 1.
DR SUPFAM; SSF82282; Homocysteine S-methyltransferase; 1.
DR SUPFAM; SSF56507; Methionine synthase activation domain-like; 1.
DR SUPFAM; SSF47644; Methionine synthase domain; 1.
DR PROSITE; PS50974; ADOMET_ACTIVATION; 1.
DR PROSITE; PS51332; B12_BINDING; 1.
DR PROSITE; PS51337; B12_BINDING_NTER; 1.
DR PROSITE; PS50970; HCY; 1.
DR PROSITE; PS50972; PTERIN_BINDING; 1.
PE 2: Evidence at transcript level;
KW Amino-acid biosynthesis; Cobalamin; Cobalt; Cytoplasm; Metal-binding;
KW Methionine biosynthesis; Methyltransferase; Phosphoprotein;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..1265
FT /note="Methionine synthase"
FT /id="PRO_0000251734"
FT DOMAIN 19..338
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 371..632
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 662..759
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 772..907
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 923..1265
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 323
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 324
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 382..384
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 449
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 470
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 537
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 579
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 585
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 591
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q99707"
FT BINDING 709
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 782..786
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 785
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /ligand_part="Co"
FT /ligand_part_id="ChEBI:CHEBI:27638"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 830
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 834
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 886
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 974
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 1172
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 1227..1228
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT MOD_RES 1264
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2Q4"
SQ SEQUENCE 1265 AA; 140478 MW; 7E1E03AB95134529 CRC64;
MAPTLQDLTP SAGMKKTLQD EIEAILQERI MVLDGGMGTM IQRHKLSEED FRGQEFKDHA
RPLKGNNDIL SITQPNVIYQ IHKEYLLAGA DIIETNTFSS TSIAQADYGL EHLAYRMNMC
SAGVARKAAE DISLQTGIKR YVAGALGPTN KTLSVSPSVE RPDYRNITFD ELVEAYKEQA
KGLLDGGVDI LLIETIFDTA NAKAALFAVQ KLFEEEYVPR PVFISGTIVD KSGRTLSGQT
GEAFVISVSH ADPLCIGLNC ALGAAEMRPF IETIGKCTTA YVLCYPNAGL PNTFGDYDET
PHVMAMHLKD FAVDGLVNIV GGCCGTTPDH IREIAEAVKN CKPRVPPATV FEGHMLLSGL
EPFRIGPYTN FVNIGERCNV AGSRRFAKLI MAGNYEEALS VAKMQVEMGA QVLDINMDDG
MLDGPSAMTR FCNFIASEPD IAKVPLCIDS SNFAVIEAGL KCCQGKCIVN SISLKEGEDD
FLEKARKIKK FGAAVVVMAF DEEGQATETD PKIRVCTRAY HLLLKKLGFN PNDIIFDPNI
LTIGTGMEEH NLYAVNFINA TKVIKETLPG AKVSGGLSNL SFSFRGMEAI REAMHGVFLY
HAIKFGMDMG IVNAGSLPVY DDIHKELLQL CEDLIWNRDP EATEKLLHYA QTQGKGGKKV
IQTDEWRNGP LEERLEYALV KGIEKYIIED TEEARLNQEK YPRPLNIIEG PLMNGMKIVG
DLFGAGKMFL PQVIKSARVM KKAVGHLIPF MEKEREETKV LTGKIEDEDP YQGTIVLATV
KGDVHDIGKN IVGVVLGCNN FRVIDLGVMT PCDKILKAAL DHKADIIGLS GLITPSLDEM
IFVAKEMERL AIKIPLLIGG ATTSRTHTAV KIAPRYSAPV IHVLDASKSV VVCSQLLDEN
LKDEYFEEIL EEYEDIRQDH YESLKERRYL TLRQARENGF HIDWLSEPPP VKPTFLGTRV
FEDYDLQKLV DYIDWKPFFD VWQLRGKYPN RGFPKIFDDK TVGEEAKKVY DDAQNMLQAL
ISQKKLQARG VVGFWPAQSI QDDIHLYAEG AVPQASEPIA TFYGLRQQAE KDSASSDPYL
CLSDFIAPLH SGIPDYLGLF AVACFGVEEL SKAYEEECDD YSSIMVKALG DRLAEAFAEE
LHERARRELW GYCSGEQLAV ADLRRLRYEG IRPAPGYPSQ PDHTEKLTVW RLADVEQRTG
IRLTESLAMA PASAVSGLYF SNLKSKYFAV GKISKDQIED YASRKNMSVA EVEKWLGPIL
GYDTD
//
