METH_DICDI
ID METH_DICDI Reviewed; 1260 AA.
AC Q54P92;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=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=mtr; ORFNames=DDB_G0284699;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
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; AAFI02000070; EAL65119.1; -; Genomic_DNA.
DR RefSeq; XP_638483.1; XM_633391.1.
DR AlphaFoldDB; Q54P92; -.
DR SMR; Q54P92; -.
DR STRING; 44689.DDB0230138; -.
DR PaxDb; Q54P92; -.
DR EnsemblProtists; EAL65119; EAL65119; DDB_G0284699.
DR GeneID; 8624734; -.
DR KEGG; ddi:DDB_G0284699; -.
DR dictyBase; DDB_G0284699; mtr.
DR eggNOG; KOG1579; Eukaryota.
DR HOGENOM; CLU_004914_2_0_1; -.
DR InParanoid; Q54P92; -.
DR OMA; ADCIAMS; -.
DR PhylomeDB; Q54P92; -.
DR Reactome; R-DDI-156581; Methylation.
DR Reactome; R-DDI-1614635; Sulfur amino acid metabolism.
DR Reactome; R-DDI-9013407; RHOH GTPase cycle.
DR Reactome; R-DDI-9759218; Cobalamin (Cbl) metabolism.
DR UniPathway; UPA00051; UER00081.
DR PRO; PR:Q54P92; -.
DR Proteomes; UP000002195; Chromosome 4.
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; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009086; P:methionine biosynthetic process; ISS:UniProtKB.
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..1260
FT /note="Methionine synthase"
FT /id="PRO_0000327799"
FT DOMAIN 13..333
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT DOMAIN 364..625
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT DOMAIN 655..749
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00667"
FT DOMAIN 766..883
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT DOMAIN 916..1256
FT /note="AdoMet activation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00346"
FT BINDING 255
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 319
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 775..779
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 778
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 823
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 827
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 879
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000250|UniProtKB:P13009"
FT BINDING 966
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1163
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1218..1219
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1260 AA; 140122 MW; 095402C1F5889CF0 CRC64;
MINSNDKNES DTFGIIRKIL SERIMVLDGA MGTEIQKFKL KDNDYRGEEF KDFPHELGGN
NDLLSLTQPH IIREIHCKYL EAGADFIETN TFNGNIFSQA DYKMEHLVKR INIESARLAK
SACEEYTKKD PSRPRFVCGA VGPTNKTASI SPSVERPEAR NVLFDELVSG YLEQVEALVE
GGIDVILVET VFDSLNCKAA LFAIEEFFKT YSPRLPVFVS GTIVDKSGRT LSGQTGEAFY
TSVASANLMV FGLNCALGAQ EMRPFLQNIS KCSECYVSCY PNAGLPNTFG GYDETPEMMA
EQIKEFAESG LLNIVGGCCG TSPDHIRAFC NAIEGIAPRA IPTLVPNTTL SGLEPLVFTK
ELNFVNVGER CNVSGSRRFA NLIKANKYEE ALSVARQQVE AGAQIIDINM DEGMIDAVAA
IQKFLFFIGS EPEISKVPIM LDSSNFDVVE AGLKCVQGKC IVNSISLKVG EELFIKQAKI
VKQYGASVVV MAFDENGQAT SKEEKVRICY RSYKILTEQV GFYPQDIIFD PNILTIATGL
EEHNNYGVEF IEATREIKAL MPLTRVSGGV SNLSFSFRGN EPLREAMHSA FLYYAIAAGM
DMGIVNAGAL PIYDDIPKDL LKLVEDAILN RTNDATEKLL EYAQANNKSE KANVEVEEWR
NKPVSERIAH ALVKGITTYI IEDTEEARNT LPSSLSVIEG PLMGGMNVVG DLFGAGKMFL
PQVIKSARVM KKAVAHLIPF MEEEKRLKRL EKGNDEAAED EPDNAGVVVL ATVKGDVHDI
GKNIVGVVLG CNNYKVIDIG VMTPCEKIVE AIIANKADVV GLSGLITPSL DEMIYVASEL
ERLKFKIPLM IGGATTSQIH TAVKISPHYS QPTVHVLDAS RSVTVVQSLL DPNNKEVFAE
DVSQQYAELR EKHYASLKDR KYTSLEKARQ HCVKVNWKTI QPVKPTFLGT QVFKEYSLEK
LVTKIDWNPF FVTWQLRGKY PNRGYPRIFN DETVGAEAKK LFDDAQTMLK EIVDKKLLNA
RGVIGFYPAN SIDEDIIIYD HNDDETRSKP IATLFGLRQQ NEKETDEPYI AIGDYIAPVS
SGVKDYIGLF AVSSGFGLED MVEKYKKEND DYSSIMAKAL ADRLAEALAE AVHEDVRREH
WAYEKDQALS NEDLFKIKYK GIRPAPGYPA QPDHTEMKTI WSLMNVNENT SIELTDHMAM
LPGAAVCGVY FSHEHAKYFS VGKITKEQIE SYASRKQITK EEAERWLSSI LSYDRLPLVK
