ID G1QTS1_NOMLE Unreviewed; 1250 AA.
AC G1QTS1;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 28-FEB-2018, sequence version 2.
DT 27-MAR-2024, entry version 82.
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:ENSNLEP00000004339.2};
OS Nomascus leucogenys (Northern white-cheeked gibbon) (Hylobates leucogenys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hylobatidae;
OC Nomascus.
OX NCBI_TaxID=61853 {ECO:0000313|Ensembl:ENSNLEP00000004339.2, ECO:0000313|Proteomes:UP000001073};
RN [1] {ECO:0000313|Ensembl:ENSNLEP00000004339.2, ECO:0000313|Proteomes:UP000001073}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Gibbon Genome Sequencing Consortium;
RL Submitted (OCT-2012) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSNLEP00000004339.2}
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; ADFV01037041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037044; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037047; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ADFV01037048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G1QTS1; -.
DR STRING; 61853.ENSNLEP00000004339; -.
DR Ensembl; ENSNLET00000004565.3; ENSNLEP00000004339.2; ENSNLEG00000003551.3.
DR eggNOG; KOG1579; Eukaryota.
DR GeneTree; ENSGT00420000029824; -.
DR HOGENOM; CLU_004914_4_0_1; -.
DR InParanoid; G1QTS1; -.
DR OMA; ADCIAMS; -.
DR TreeFam; TF312829; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000001073; Chromosome 5.
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:UP000001073};
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 22..341
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 374..635
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 665..762
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 775..910
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 907..1250
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 263
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 326
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 327
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 712
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 785..789
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 788
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 833
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 837
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 889
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 959
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1157
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1212..1213
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1250 AA; 138917 MW; 27442051D5B6774B CRC64;
ELQALRDFSQ PTELSGLKKT LRDEIDAILR KRIMVLDGGM GTMIQRQKLN EEHFRGQEFK
DHARPLKGNN DILSITRPDV IYQIHKEYLL AGADIIETNT FSSTSIAQAD YGLEHLAYQM
NKCSAGVARK AAEEITLQTG IKRFVAGALG PTNKTLSVSP SVERPDYRNI TFDELVEAYR
EQAKGLLDGG VDILLIETIF DTANAKAALF ALQNLFEEKY APRPIFISGT IVDKSGRTLS
GQTGEGFVVS VSHGEPLCIG LNCALGAAEM RPFIEIIGKC TTAYVLCYPN AGLPNTFGDY
DETPSVMAKH LKDFAMDGLV NIVGGCCGST PDHIREIAEA VKNCKPRVPP ATVFEGHMLL
SGLEPFRIGP YTNFVNIGER CNVAGSRKFA KLIMAGNYEE ALCVAKVQVE MGAQVLDVNM
DDGMLDGPSA MTRFCNLIAS EPDIAKVPLC IDSSNFAVID AGLKCCQGKC IVNSISLKEG
EDDFLEKARK IKKYGAAVVV MAFDEEGQAT ETDTKIRVCT RAYHLLVKKL DFNPNDIIFD
PNILTIGTGM EEHNLYAINF IHATKVIKET LPGARISGGL SNLSFSFRGM EAIREAMHGV
FLYHAIKSGM DMGIVNAGNL PVYDDIHKEL LQLCEDLIWN KDPEATEKLL RYAQTQGTGG
KKVIQTDEWR NGPVEERLEY ALVKGIEKHI IEDTEEARLN QEKYPRPLNI IEGPLMNGMK
IVGDLFGAGK MFLPQVIKSA RVMKKAVGHL IPFMEKEREE TRVLNGTVEE EDPYQGTIVL
ATVKGDVHDI GKNIVGVVLG CNNFRVIDLG VMTPCDKILK AALDHKADII GLSGLITPSL
DEMIFVAKEM ERLAIKIPLL IGGATTSKTH TAVKIAPRYS APVIHVLDAS KSVVVCSQLL
DENLKDEYFE EIMEEYEDIR QDHYESLKER RYLPLMRPMF IGTQVFEDYD LQKLVDYIDW
KPFFDVWQLR GKYPNRGFPK IFNDKTVGGE AKKVYDDAHN MLNTLISQKK LRARGVVGFW
PAQSIQDDIH LYAEGAVPQA AEPIATFYGL RQQAEKDSAS TEPYYCLSDF IAPLHSGIRD
YLGLFAVACF GVEELSKAYE DDGDDYSSIM VKALGDRLAE AFAEELHERV RRELWAYCGS
EQLDVADLRR LRYKGIRPAP GYPSQPDHTE KLTMWRLADI EQSTGIRLTE SLAMAPASAV
SGLYFSNLKS TYFAVGKISK DQVEDYALRK NISVAEVEKW LGPILGYDTD
//
