ID METH_CAEEL Reviewed; 1249 AA. AC Q09582; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 167. DE RecName: Full=Probable methionine synthase; DE EC=2.1.1.13; DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase; DE AltName: Full=Vitamin-B12 dependent methionine synthase; DE Short=MS; GN Name=metr-1; ORFNames=R03D7.1; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for investigating RT biology."; RL Science 282:2012-2018(1998). CC -!- FUNCTION: Catalyzes the transfer of a methyl group from methyl- CC cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and CC methionine. Subsequently, remethylates the cofactor using CC methyltetrahydrofolate (By similarity). {ECO:0000250}. 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 -!- COFACTOR: CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115; CC Evidence={ECO:0000250}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250}; CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1. 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). {ECO:0000250}. CC -!- MISCELLANEOUS: L-homocysteine is bound via the zinc atom. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z46828; CAA86855.1; -; Genomic_DNA. DR PIR; T23868; T23868. DR RefSeq; NP_496353.1; NM_063952.4. DR AlphaFoldDB; Q09582; -. DR SMR; Q09582; -. DR BioGRID; 39991; 4. DR DIP; DIP-26122N; -. DR IntAct; Q09582; 1. DR STRING; 6239.R03D7.1.1; -. DR EPD; Q09582; -. DR PaxDb; 6239-R03D7-1; -. DR PeptideAtlas; Q09582; -. DR EnsemblMetazoa; R03D7.1.1; R03D7.1.1; WBGene00010988. DR GeneID; 174681; -. DR KEGG; cel:CELE_R03D7.1; -. DR UCSC; R03D7.1; c. elegans. DR AGR; WB:WBGene00010988; -. DR WormBase; R03D7.1; CE01609; WBGene00010988; metr-1. DR eggNOG; KOG1579; Eukaryota. DR GeneTree; ENSGT00420000029824; -. DR HOGENOM; CLU_004914_2_0_1; -. DR InParanoid; Q09582; -. DR OMA; ADCIAMS; -. DR OrthoDB; 66796at2759; -. DR PhylomeDB; Q09582; -. DR Reactome; R-CEL-156581; Methylation. DR Reactome; R-CEL-1614635; Sulfur amino acid metabolism. DR Reactome; R-CEL-9013407; RHOH GTPase cycle. DR Reactome; R-CEL-9759218; Cobalamin (Cbl) metabolism. DR UniPathway; UPA00051; UER00081. DR PRO; PR:Q09582; -. DR Proteomes; UP000001940; Chromosome II. DR Bgee; WBGene00010988; Expressed in larva and 4 other cell types or tissues. 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 3: Inferred from homology; KW Amino-acid biosynthesis; Cobalamin; Cobalt; Metal-binding; KW Methionine biosynthesis; Methyltransferase; Reference proteome; Repeat; KW S-adenosyl-L-methionine; Transferase; Zinc. FT CHAIN 1..1249 FT /note="Probable methionine synthase" FT /id="PRO_0000204531" FT DOMAIN 1..327 FT /note="Hcy-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT DOMAIN 360..621 FT /note="Pterin-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334" FT DOMAIN 652..749 FT /note="B12-binding N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667" FT DOMAIN 762..897 FT /note="B12-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666" FT DOMAIN 913..1249 FT /note="AdoMet activation" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346" FT BINDING 249 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT BINDING 312 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT BINDING 313 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333" FT BINDING 699 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 772..776 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 775 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 820 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 824 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 876 FT /ligand="methylcob(III)alamin" FT /ligand_id="ChEBI:CHEBI:28115" FT /evidence="ECO:0000250|UniProtKB:P13009" FT BINDING 963 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 1157 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 1211..1212 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" SQ SEQUENCE 1249 AA; 138899 MW; 4D16028AD02CD550 CRC64; MTRSSLFEEL AEIAKERIMI IDGAMGTMIQ REYMEEEDFR GEILKDHDKP LKGNNDLLSI TRPDIIYKIH KLYLEAGADF VETNTFSGTT IAQADYRCEH LVHEINYQSA LVARRACDDV GAATGRRRYV CGAIGPTNRT LSISPSVEKP DFRNVTFQEL VKAYGDQARS LIQGGVDVLL VETVFDSANA KAALFAIRTL FEDEGVPEMP VFLSGTIVDM SGRTLSGQTG EAFLVSTKQG KPMAVGLNCA LGAKDMRQFV DNMSKWSDSF IICYPNAGLP NALGGYDETP EEMADVLREF ARDGLVNIIG GCCGTTPDHI NAMYKAVQGI TPRVPPQDPH AGKMLLSGLE PSIVGPETNF VNIGERCNVA GSRRFCNLIK NENYDTAIDV ARVQVDSGAQ ILDVNMDDGL LDGPYAMSKF LRLISSEPDV AKIPVCIDSS DFDVIIAGLE STQGKCVVNS ISLKEGEEKF KERARIIKRY GAAVVVMAFD EQGQAAETDP KFEICERSYR ILTEEVGFNP NDIIFDANIL TIATGMEEHS NYGMYFIEAA RMIRENLPGA HVSGGVSNIS FSFRGMEAIR EAMHSVFLFY AIKAGMDMGI VNAGALPVYE DIDKPLLQLL EDLLFNRDPE ATEKLLVAAQ EMKKDGKKAD TKTDEWRSLT VEERLKFALV KGVDQFVVAD TEEARQNTAK YPRPLNVIER PLMDGMAVVG ELFGAGKMFL PQVIKSARVM KKAVAHLLPF MEIERQANIE TMGLAEDESP YQGTVVIATV KGDVHDIGKN IVSVVLGCNN FKVVDLGVMT PCENIIKAAI EEKADFIGLS GLITPSLDEM VYVAKEMNRV GLNIPLLIGG ATTSKTHTAV KISPRYPHPV VHCLDASKSV VVCSSLSDMS VRDAFLQDLN EDYEDVRQEH YASLKDRRFT DLNKTREKKF KIDWDKFTAV KPSFVGRREY QNFDLNELIP YIDWKPFFDV WQLRGKYPNR SYPKIFDDAD VGAEAKKVFD DAQTWLKKLI DEKILVANAV VSFLPAASEG DDMHVYDPET GNKLDTFYGL RQQSGREHDQ PHFCLSDFIK PLKNGVPDDY LGLFACTAGL GAEEYCKTLE KNHDDYASIM VKALADRLAE AYAEYLHKEV RTTLWGYSTN EDLTESDLLS IKYQGIRPAC GYPSQPDHTE KRTLWKLLEA EKNGIGLTEH LAMLPAASVS GLYFANPQSE YFAVGKIDQD QVIDYAARKN VPKEEVERWL SPILGYDTD //