METH_CAEEL
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 03-AUG-2022, entry version 159.
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}.
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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; 3.
DR DIP; DIP-26122N; -.
DR IntAct; Q09582; 1.
DR STRING; 6239.R03D7.1; -.
DR EPD; Q09582; -.
DR PaxDb; Q09582; -.
DR PeptideAtlas; Q09582; -.
DR PRIDE; 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 CTD; 174681; -.
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; 731388at2759; -.
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 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:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0042558; P:pteridine-containing compound metabolic process; IEA:InterPro.
DR CDD; cd02069; methionine_synthase_B12_BD; 1.
DR Gene3D; 1.10.1240.10; -; 1.
DR Gene3D; 3.10.196.10; -; 1.
DR Gene3D; 3.20.20.20; -; 1.
DR Gene3D; 3.20.20.330; -; 1.
DR InterPro; IPR003759; Cbl-bd_cap.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR InterPro; IPR011005; Dihydropteroate_synth-like.
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 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; SSF47644; SSF47644; 1.
DR SUPFAM; SSF51717; SSF51717; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR SUPFAM; SSF56507; SSF56507; 1.
DR SUPFAM; SSF82282; SSF82282; 1.
DR TIGRFAMs; TIGR02082; metH; 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
