ID A0A151M2T9_ALLMI Unreviewed; 1264 AA.
AC A0A151M2T9;
DT 08-JUN-2016, integrated into UniProtKB/TrEMBL.
DT 08-JUN-2016, sequence version 1.
DT 27-MAR-2024, entry version 46.
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|EMBL:KYO18845.1};
GN ORFNames=Y1Q_0009255 {ECO:0000313|EMBL:KYO18845.1};
OS Alligator mississippiensis (American alligator).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Crocodylia; Alligatoridae; Alligatorinae;
OC Alligator.
OX NCBI_TaxID=8496 {ECO:0000313|EMBL:KYO18845.1};
RN [1] {ECO:0000313|EMBL:KYO18845.1, ECO:0000313|Proteomes:UP000050525}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=KSC_2009_1 {ECO:0000313|EMBL:KYO18845.1};
RX PubMed=22293439; DOI=10.1186/gb-2012-13-1-415;
RA St John J.A., Braun E.L., Isberg S.R., Miles L.G., Chong A.Y., Gongora J.,
RA Dalzell P., Moran C., Bed'hom B., Abzhanov A., Burgess S.C., Cooksey A.M.,
RA Castoe T.A., Crawford N.G., Densmore L.D., Drew J.C., Edwards S.V.,
RA Faircloth B.C., Fujita M.K., Greenwold M.J., Hoffmann F.G., Howard J.M.,
RA Iguchi T., Janes D.E., Khan S.Y., Kohno S., de Koning A.J., Lance S.L.,
RA McCarthy F.M., McCormack J.E., Merchant M.E., Peterson D.G., Pollock D.D.,
RA Pourmand N., Raney B.J., Roessler K.A., Sanford J.R., Sawyer R.H.,
RA Schmidt C.J., Triplett E.W., Tuberville T.D., Venegas-Anaya M.,
RA Howard J.T., Jarvis E.D., Guillette L.J.Jr., Glenn T.C., Green R.E.,
RA Ray D.A.;
RT "Sequencing three crocodilian genomes to illuminate the evolution of
RT archosaurs and amniotes.";
RL Genome Biol. 13:415-415(2012).
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}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:KYO18845.1}.
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DR EMBL; AKHW03006780; KYO18845.1; -; Genomic_DNA.
DR RefSeq; XP_019335293.1; XM_019479748.1.
DR AlphaFoldDB; A0A151M2T9; -.
DR STRING; 8496.A0A151M2T9; -.
DR GeneID; 102562610; -.
DR KEGG; amj:102562610; -.
DR CTD; 4548; -.
DR eggNOG; KOG1579; Eukaryota.
DR OrthoDB; 66796at2759; -.
DR PhylomeDB; A0A151M2T9; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000050525; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; 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:UP000050525};
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 20..339
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 372..632
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 663..760
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 261
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 324
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 325
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 710
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; 140961 MW; 0D9F4BFBEA5D6E85 CRC64;
MSPTSHGLRD QPVDTTKSLK DEIESVLLER IMVLDGGMGT MIQQHALSEE DFRGQEFQDH
PKPLKGNNDL LSITQPDIIY KIHKEYLLSG ADIIETNTFS STRVAQADYG LEDLVYRLNR
ISAQVARKAA DDVTTLTGCK RYVAGAMGPT NRTLSLSPSV ERPDYRNITF DELVEAYQEQ
AKGLLDGGVD ILLVETIFDT ANAKAALFAL RKLFKEEYKP KPIFVSGTII DKSGRTLSGQ
TGEAFVISIS HCEPLCIGLN CALGAIEMRP FIETIGKCTT AFIICYPNAG LPNTFGGYDE
TPEMTAEHIK SFALDGLVNI VGGCCGTTPA HIREIAEAVK ACKPRVPPSS FSDGYMLLSG
LEPFRIGPYT NFVNIGERCN VAGSRKFAKL IMKDNYEEAL SVAKAQVEMG AQILDINMDD
GMLDGPNAMA RFCKLIASEP DIAKVPLCID SSNFSVIEAG LKCCQGKCIV NSISLKEGEE
DFLEKGRKIK LYGGAVVVMA FDEVGQATET ETKVAVCTRA YHLLVEKVGF NPNDIIFDPN
ILTIGTGMEE HNLYAVNFMK ATKTIKEMLP GARVSGGLSN LSFSFRGMDA IREAMHGVFL
YHAIKYGMDM GIVNAGNLPV YDDIPKDLLT LCDNLIWNKD PDGTEKLLRY AQTHTQGGKK
VVQTDEWRNS PVEERLEYAL IKGIEKYVIE DTEEARLNHE KYPRPLNIIE GPLMSGMQVV
GDLFGAGKMF LPQVIKSARV MKKAVGHLIP YMEKEREEMR SGTIEEEDPY HGTIVLATVK
GDVHDIGKNI VGVVLGCNNF RVIDLGVMTP CDKILRAAIE NKADIIGLSG LITPSLDEMI
FVAKEMQRLE IKIPLLIGGA TTSKTHTAVK IAPRYSAPVI HVLDASKSVV VCSQLLDENQ
KEDFFEEVLE EYDDIRQEHY ESLKERKYLS LEQARRKGFH NDWLSDCKPV KPRFIGTQVF
EDYDLHKLVE YIDWKPFFDV WQLRGKYPNR GFPKIFNDKV VGEEAKRVYN DAQNLLKTLI
NQKKLRARGL VGFWPAQSVQ DDVYLYASEE AVQFAEPIAK FYGLRQQAEK DSACTDPYYC
LSDFIAPLDS GVHDYLGLFA VACFGVDELC KEFEKQCDDY NSIMVKALGD RLAEAFAEEL
HERVRKELWA YCNDEQLDIA DLRRIRYEGI RPAPGYPSQP DHTEKLTMWK LASIKEATDI
GLTESLAMTP ASAISGLYFA NPKSKYFAVG KICKDQVEDY ALRKNLSVTE VEKWLGPILG
YDLG
//
