ID A0A0D9RBF8_CHLSB Unreviewed; 1264 AA.
AC A0A0D9RBF8;
DT 27-MAY-2015, integrated into UniProtKB/TrEMBL.
DT 27-MAY-2015, sequence version 1.
DT 27-MAR-2024, entry version 54.
DE RecName: Full=Methionine synthase {ECO:0000256|ARBA:ARBA00012032, ECO:0000256|PIRNR:PIRNR000381};
DE EC=2.1.1.13 {ECO:0000256|ARBA:ARBA00012032, ECO:0000256|PIRNR:PIRNR000381};
DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|PIRNR:PIRNR000381};
GN Name=MTR {ECO:0000313|Ensembl:ENSCSAP00000005947.1};
OS Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=60711 {ECO:0000313|Ensembl:ENSCSAP00000005947.1, ECO:0000313|Proteomes:UP000029965};
RN [1] {ECO:0000313|Ensembl:ENSCSAP00000005947.1, ECO:0000313|Proteomes:UP000029965}
RP NUCLEOTIDE SEQUENCE.
RA Warren W., Wilson R.K.;
RL Submitted (MAR-2014) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSCSAP00000005947.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|PIRNR:PIRNR000381}.
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:0000256|PIRNR:PIRNR000381};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|ARBA:ARBA00001947,
CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE-ProRule:PRU00333};
CC -!- COFACTOR:
CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC Evidence={ECO:0000256|ARBA:ARBA00001956,
CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1};
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:0000256|ARBA:ARBA00005178, ECO:0000256|PIRNR:PIRNR000381}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|PIRNR:PIRNR000381}.
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. {ECO:0000256|PIRNR:PIRNR000381}.
CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase
CC family. {ECO:0000256|ARBA:ARBA00010398}.
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DR EMBL; AQIB01131440; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_007988081.1; XM_007989890.1.
DR AlphaFoldDB; A0A0D9RBF8; -.
DR STRING; 60711.ENSCSAP00000005947; -.
DR Ensembl; ENSCSAT00000007781.1; ENSCSAP00000005947.1; ENSCSAG00000009702.1.
DR GeneID; 103230818; -.
DR CTD; 4548; -.
DR eggNOG; KOG1579; Eukaryota.
DR GeneTree; ENSGT00420000029824; -.
DR OMA; ADCIAMS; -.
DR OrthoDB; 66796at2759; -.
DR UniPathway; UPA00051; UER00081.
DR BioGRID-ORCS; 103230818; 0 hits in 9 CRISPR screens.
DR Proteomes; UP000029965; Chromosome 25.
DR Bgee; ENSCSAG00000009702; Expressed in fibroblast and 7 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008705; F:methionine synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009235; P:cobalamin metabolic process; IEA:Ensembl.
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 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 {ECO:0000256|ARBA:ARBA00022605,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Cobalamin {ECO:0000256|ARBA:ARBA00022628, ECO:0000256|PIRNR:PIRNR000381};
KW Cobalt {ECO:0000256|ARBA:ARBA00023285, ECO:0000256|PIRNR:PIRNR000381};
KW Cytoplasm {ECO:0000256|PIRNR:PIRNR000381};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Reference proteome {ECO:0000313|Proteomes:UP000029965};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691,
KW ECO:0000256|PIRNR:PIRNR000381};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRNR:PIRNR000381}.
FT DOMAIN 18..337
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 370..631
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 661..758
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 771..906
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 922..1264
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT ECO:0000256|PROSITE-ProRule:PRU00333"
FT BINDING 322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT ECO:0000256|PROSITE-ProRule:PRU00333"
FT BINDING 323
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1,
FT ECO:0000256|PROSITE-ProRule:PRU00333"
FT BINDING 708
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 781..785
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 784
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:0000256|PIRSR:PIRSR000381-1"
FT BINDING 829
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 833
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 885
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 973
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1171
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1226..1227
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1264 AA; 140534 MW; 389C831403CBD0D9 CRC64;
MSPALQDLSQ PGLKKTPRDE IDAILRKRVM VLDGGMGTMI QRQKLNEEHF RGQEFKDHAR
PLKGNNDILS ITQPDVIYQI HKEYLLAGAD IIETNTFSST SIAQADYGLE HLAYQMNKCS
AGVARKAAEE ITLQTGIKRF VAGALGPTNK TLSVSPSVER PDYRNITFDE LVEAYQEQAK
GLLDGGVDIL LIETIFDTAN AKAAVFALQN LFEEKYAPRP IFISGTIVDK SGRTLSGQTG
EAFVISLSHA EPLCIGLNCA LGAAEMRPFI EMIGKCTTAY VLCYPNAGLP NTFGDYDETP
SMMAKHLKDF AMDGLVNIVG GCCGSTPAHI REIAEAVKNC KPRVPPATVF EGHMLLSGLE
PFRIGQYTNF VNIGERCNVA GSRKFAKLIM AGNYEEALGV ARVQVEMGAQ VLDINMDDGM
LDGPSAMTRF CNLIASEPDI AKVPLCIDSS NFAVIEAGLK CCQGKCIVNS ISLKEGEDDF
LEKARKIKKF GAAMVVMAFD EEGQATETDT KISVCTRAYH LLVKKLGFNP NDIIFDPNIL
TIGTGMEEHN LYAINFIHAT KVIKETLPGA RISGGLSNLS FSFRGMEAIR EAMHGVFLYH
AIKSGMDMGI VNAGNLPVYD DIHKELLQLC EDLIWNKDPE ATEKLLRYAQ TQGTGGKKVI
QTDEWRNGPV EERLEYALVK GIEKHIIEDT EEARLNQERY PRPLNIIEGP LMNGMKIVGD
LFGAGKMFLP QVIKSARVMK KAVGHLIPFM EKEREETRVL NGTIEEEDPY QGTIVLATVK
GDVHDIGKNI VGVVLGCNNF RVIDLGVMTP CDKILKAALD HKADIIGLSG LITPSLDEMI
FVAKEMERLA IKIPLLIGGA TTSRTHTAVK IAPRYSAPVI HVLDASKSVV VCSQLLDENL
KDEYFEEIME EYEDIRQDHY ESLKERRYLP LNQARKSGFQ MDWLSEPHPV KPTFIGTQVF
EDYDLQKLVD YIDWKPFFDV WQLRGKYPNR GFPKIFNDKT VGEEAKKVYD DAQNMLNTLI
NQKKLQARGV VGFWPAQSIQ DDIHLYTESA VPQAAEPIAT FYGLRQQAEK DSASTEPYYC
LSDFIAPLHS GIRDYLGLFA VACFGVEELS KAYEDDGDDY SSIMVKALGD RLAEAFAEEL
HERVRRELWA YCGSEQLDVA DLRRLRYEGI RPAPGYPSQP DHTEKLTMWR LADIEQSTGI
RLTESLAMAP ASAVSGLYFS NLKSKYFAVG KISKDQVEDY ALRKNMSVAE VEKWLGPILG
YDTE
//
