ID A0A2T9YIS9_9FUNG Unreviewed; 1271 AA.
AC A0A2T9YIS9;
DT 18-JUL-2018, integrated into UniProtKB/TrEMBL.
DT 18-JUL-2018, sequence version 1.
DT 27-MAR-2024, entry version 24.
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 ORFNames=BB559_003805 {ECO:0000313|EMBL:PVU92219.1};
OS Furculomyces boomerangus.
OC Eukaryota; Fungi; Fungi incertae sedis; Zoopagomycota; Kickxellomycotina;
OC Harpellomycetes; Harpellales; Harpellaceae; Furculomyces.
OX NCBI_TaxID=61424 {ECO:0000313|EMBL:PVU92219.1, ECO:0000313|Proteomes:UP000245699};
RN [1] {ECO:0000313|EMBL:PVU92219.1, ECO:0000313|Proteomes:UP000245699}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AUS-77-4 {ECO:0000313|EMBL:PVU92219.1,
RC ECO:0000313|Proteomes:UP000245699};
RX PubMed=29764946;
RA Wang Y., Stata M., Wang W., Stajich J.E., White M.M., Moncalvo J.M.;
RT "Comparative Genomics Reveals the Core Gene Toolbox for the Fungus-Insect
RT Symbiosis.";
RL MBio 9:e00636-e00618(2018).
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|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 -!- 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:PVU92219.1}.
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DR EMBL; MBFT01000381; PVU92219.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2T9YIS9; -.
DR STRING; 61424.A0A2T9YIS9; -.
DR UniPathway; UPA00051; UER00081.
DR Proteomes; UP000245699; Unassembled WGS sequence.
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 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:UP000245699};
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 12..332
FT /note="Hcy-binding"
FT /evidence="ECO:0000259|PROSITE:PS50970"
FT DOMAIN 365..630
FT /note="Pterin-binding"
FT /evidence="ECO:0000259|PROSITE:PS50972"
FT DOMAIN 656..753
FT /note="B12-binding N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51337"
FT DOMAIN 780..915
FT /note="B12-binding"
FT /evidence="ECO:0000259|PROSITE:PS51332"
FT DOMAIN 931..1271
FT /note="AdoMet activation"
FT /evidence="ECO:0000259|PROSITE:PS50974"
FT BINDING 254
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 317
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 318
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 703
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 790..794
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 793
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 838
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 842
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 894
FT /ligand="methylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:28115"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 983
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1179
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
FT BINDING 1234..1235
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2"
SQ SEQUENCE 1271 AA; 140287 MW; B3825B6E66F7284E CRC64;
MNNINAKRDE VTKYIENELS RRIMIIDGAM GTQIQNLKLT EEDFRGEIFK NHPKSLKGNN
DILVLTKPDD IYQIHKNYLL AGADFIETNT FSGTSIAQLD YGLEDYAYQI NKAASQIAKK
ACEDVTAQTP DRPRFVLGAV GPTNRTLSIS PSVEQPSFRN TTFDLLSQAY KEQVKGLLDG
GADVLLVETI FDTLNAKAAI FAIESVFEET NTRVPIFISG TIVDLSGRTL SGQTGEAFVT
SVLHVEPMAL GLNCALGATQ MKPFITNLSR FSPKYTICYP NAGLPNAFGG YDESPESMAE
NMKEFAQEGI VNLIGGCCGT SPAHIKAMYE ACKDIKPRVP GPDIRKTKMI LSGLETSIFD
EHSNFINIGE RCNVAGSKKF SNHILRGEFE DALAIAKSQV ENGAQILDIN MDEGMLDGKL
AMTTFLNLLA TEPDVARIPL MIDSSNFEVV EAGLKCAQGK CIVNSISLKE GVEDFLKKAR
VVKRYGAAVV VMAFDSEGQA VDAKRKFEIC KRSYDILVNE VGFDPQDIVF DPNILTICTG
MEEHNGYAVE FINAIKDIKK HLPGAKVSGG ISNLSFSFRG KEVIRQAMHS VFLYHAIKAG
MDMGIVNPGF LTIYDEIPKD LLEICENAVW NKDPNSTELL LEYAQRKGAG AKAVVEDEEW
RRGTVTDRLA HALVKGITKY IIEDVEEARL DTASFPKPLN IIEGPLMKGM GIVGDLFGSG
KMFLPQVIKS ARVMKSAVAY LIPFMEAERL KALDALKEAS GNSEIEESSG ADEIDYSMYN
GTVVLATVKG DVHDIGKNIV GVVLGCNNYR IVDLGVMTPA EKIIEAAIKE KADIVGLSGL
ITPSLDEMIN TANMMEKAGL KVPLMIGGAT TSKAHTAVKI DLQYSQPVVH VLDASRTVVV
VSNLLDYELK SDYTEEIKEE YDDIREEYYE SLKDTVYLPI DEARKNSFKI DWSVPSNQPP
KPNFVGTKAI TDIDLETVVP FIDWNPFFQI FQLRGKYPNR GYPKLFNDPA VGPEAKKLFE
DALSMMKTIF KSKKAFGSAV IGIYPANSVG DDIVVYKDES RSEIATTFHG IRQQEERNRG
NNEPYFCLSD FIAPSSTGIK DYVGGVAVSA GFGFSEIAKE YEDNNDDYSS IIVKALADRL
AEALIEKTHL DIRKEYWGYS LDEELSATDL HSLKYQGIRP APGYPSQPDH SEMANLWSLL
RVSEQTDIKL TESYMMVPAA SVSALVFAHP LSKYFATGKI QKDQVVDYAK RKNIPVETAE
KNIRSIVSYD N
//
