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Database: UniProt
Entry: S9U2J8_9TRYP
LinkDB: S9U2J8_9TRYP
Original site: S9U2J8_9TRYP 
ID   S9U2J8_9TRYP            Unreviewed;       906 AA.
AC   S9U2J8;
DT   16-OCT-2013, integrated into UniProtKB/TrEMBL.
DT   16-OCT-2013, sequence version 1.
DT   24-JAN-2024, entry version 43.
DE   RecName: Full=Methionine synthase {ECO:0000256|PIRNR:PIRNR000381};
DE            EC=2.1.1.13 {ECO:0000256|PIRNR:PIRNR000381};
DE   AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|PIRNR:PIRNR000381};
GN   ORFNames=ADEAN_000971300 {ECO:0000313|EMBL:CAD2222173.1};
OS   Angomonas deanei.
OC   Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC   Trypanosomatida; Trypanosomatidae; Strigomonadinae; Angomonas.
OX   NCBI_TaxID=59799 {ECO:0000313|EMBL:CAD2222173.1, ECO:0000313|Proteomes:UP000515908};
RN   [1] {ECO:0000313|EMBL:CAD2222173.1, ECO:0000313|Proteomes:UP000515908}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Crithidia deanei Carvalho (ATCC PRA-265)
RC   {ECO:0000313|Proteomes:UP000515908};
RA   Newling K., Davey J., Forrester S.;
RL   Submitted (AUG-2020) to the EMBL/GenBank/DDBJ databases.
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. {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|PIRNR:PIRNR000381};
CC   -!- COFACTOR:
CC       Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115;
CC         Evidence={ECO:0000256|PIRNR:PIRNR000381,
CC         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|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; LR877168; CAD2222173.1; -; Genomic_DNA.
DR   AlphaFoldDB; S9U2J8; -.
DR   EnsemblProtists; EPY24263; EPY24263; AGDE_12435.
DR   EnsemblProtists; EPY25007; EPY25007; AGDE_12067.
DR   VEuPathDB; TriTrypDB:ADEAN_000971300; -.
DR   OrthoDB; 66796at2759; -.
DR   UniPathway; UPA00051; UER00081.
DR   Proteomes; UP000515908; Chromosome 24.
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: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; 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.
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   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; 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; PS50972; PTERIN_BINDING; 1.
PE   3: Inferred from homology;
KW   Amino-acid biosynthesis {ECO:0000256|PIRNR:PIRNR000381};
KW   Cobalamin {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1};
KW   Cobalt {ECO:0000256|ARBA:ARBA00023285, ECO:0000256|PIRNR:PIRNR000381};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW   ECO:0000256|PIRNR:PIRNR000381};
KW   Methionine biosynthesis {ECO:0000256|PIRNR:PIRNR000381};
KW   Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW   ECO:0000256|PIRNR:PIRNR000381};
KW   Reference proteome {ECO:0000313|Proteomes:UP000515908};
KW   Repeat {ECO:0000256|ARBA:ARBA00022737};
KW   S-adenosyl-L-methionine {ECO:0000256|PIRNR:PIRNR000381,
KW   ECO:0000256|PIRSR:PIRSR000381-2};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381};
KW   Zinc {ECO:0000256|PIRNR:PIRNR000381}.
FT   DOMAIN          12..293
FT                   /note="Pterin-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS50972"
FT   DOMAIN          314..410
FT                   /note="B12-binding N-terminal"
FT                   /evidence="ECO:0000259|PROSITE:PS51337"
FT   DOMAIN          423..557
FT                   /note="B12-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS51332"
FT   DOMAIN          572..906
FT                   /note="AdoMet activation"
FT                   /evidence="ECO:0000259|PROSITE:PS50974"
FT   BINDING         360
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         433..437
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         436
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         481
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         485
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         536
FT                   /ligand="methylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:28115"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         623
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         815
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT   BINDING         870..871
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ   SEQUENCE   906 AA;  100388 MW;  602F8B2FD84B68FB CRC64;
     MVISGLETLE FTDLIGFCNV GERCNISGSL QFKRLVKDGK WEECLAVARK QVEDGAMVID
     VNMDDGLVDG VVAMTRFLNM LASDPEVARV PLMIDSSKFH VIEAGLKCTQ GKPIVNSISL
     KVGEEEFLRQ AALIRRYGAA VVVMAFDEDG QAADCENKIR ICKRAYDLLV EHDFPPEDII
     FDPNVLTICT GMEEHNGYAM DFMNAAKWIK ENLPYAKVSG GLSNLSFSFR GLEPLRMAMH
     SAFLKDMIEK RHIDMAIVNA GALPVYTDID PKLLELVENA IYNRSPSASD ALLAFAEELK
     ASGTNTGGAE KKKEVDAWRK TSVEERLSYA LVKGIVEFVD ADVEEARTCG KFAKPLEIIE
     GPLMNGMAQV GDLFGSGKMF LPQVIKSARV MKKAVAVLIP YMEAEKAALR RAAGESGEGA
     SKPKRVLMAT VKGDVHDIGK NIVGVVLGCN SYEVIDLGVM VPCEKIIAAA REHEVDVIGL
     SGLITPSLDE MVHVAKQLKK ENITIPLMVG GATTSKQHTA VKIQPHYPKT VHVLDASKSV
     VTVNNMLKDN EEEFWEEVHE TYKEIAEEYL ANIKDRVYKP LSFCRENAFK IDFAANPPAP
     KPKTLGTITL DDYSLETIAS RIDWNPFFSV WQIRGTYPNR GYPKLFNCAT VGEEAKRLFD
     DAQTMMADIM STRAFHARAV ITLFPANSVG DDIEIYTDDT RTKTSGVFYG LRQQAEKEKG
     EPYLCLSDFI APKGVAPDYM GSVAIGIFGA DEMVARFEKE NDGYRSIMVK ALADRFAEAF
     TEEVHRLIRT EYWGYVEKEA ADTADLIQMQ YQGIRPAPGY PSQPDHTEMA TMWKIGEVEA
     RSGIKLSESN AMMPASSVSA LIFAHPQSKY FAVGKILEDQ VADYSKRKGW TLEEGEKHLR
     AILSYD
//
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