MTRR_BOVIN
ID MTRR_BOVIN Reviewed; 695 AA.
AC Q4JIJ2;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Methionine synthase reductase;
DE Short=MSR;
DE EC=1.16.1.8 {ECO:0000250|UniProtKB:Q9UBK8};
DE AltName: Full=Aquacobalamin reductase;
DE Short=AqCbl reductase;
GN Name=MTRR;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Palin M.F., Beaudry D., Charest R., Girard C.;
RT "Interactions of folic acid-vitamin B12-methionine: effects on liver
RT metabolism and production of dairy cows.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Key enzyme in methionine and folate homeostasis responsible
CC for the reactivation of methionine synthase (MTR/MS) activity by
CC catalyzing the reductive methylation of MTR-bound cob(II)alamin.
CC Cobalamin (vitamin B12) forms a complex with MTR to serve as an
CC intermediary in methyl transfer reactions that cycles between MTR-bound
CC methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional
CC oxidative escape of the cob(I)alamin intermediate during the catalytic
CC cycle leads to the inactive cob(II)alamin species. The processing of
CC cobalamin in the cytosol occurs in a multiprotein complex composed of
CC at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle
CC safely and efficiently cobalamin towards MTR in order to produce
CC methionine (By similarity). Also necessary for the utilization of
CC methyl groups from the folate cycle, thereby affecting
CC transgenerational epigenetic inheritance (By similarity). Also acts as
CC a molecular chaperone for methionine synthase by stabilizing apoMTR and
CC incorporating methylcob(III)alamin into apoMTR to form the holoenzyme.
CC Also serves as an aquacob(III)alamin reductase by reducing
CC aquacob(III)alamin to cob(II)alamin; this reduction leads to
CC stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR
CC holoenzyme (By similarity). {ECO:0000250|UniProtKB:Q8C1A3,
CC ECO:0000250|UniProtKB:Q9UBK8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 methylcob(III)alamin-[methionine synthase] + NADP(+)
CC + 2 S-adenosyl-L-homocysteine = 2 cob(II)alamin-[methionine synthase]
CC + NADPH + 2 S-adenosyl-L-methionine; Xref=Rhea:RHEA:23908, Rhea:RHEA-
CC COMP:14714, Rhea:RHEA-COMP:14715, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16304, ChEBI:CHEBI:28115, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789; EC=1.16.1.8;
CC Evidence={ECO:0000250|UniProtKB:Q9UBK8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + 2 cob(II)alamin + 2 H(+) + 2 H2O = AH2 + 2
CC aquacob(III)alamin; Xref=Rhea:RHEA:20752, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15852,
CC ChEBI:CHEBI:16304, ChEBI:CHEBI:17499;
CC Evidence={ECO:0000250|UniProtKB:Q9UBK8};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20754;
CC Evidence={ECO:0000250|UniProtKB:Q9UBK8};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9UBK8};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q9UBK8};
CC -!- SUBUNIT: Forms a multiprotein complex with MMACHC, MMADHC AND MTR.
CC {ECO:0000250|UniProtKB:Q9UBK8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UBK8}.
CC -!- MISCELLANEOUS: It is debated whether the reduction of free
CC aquacob(II)alamin occurs spontaneously or is enzyme catalyzed.
CC {ECO:0000305}.
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DR EMBL; DQ084520; AAY86763.1; -; mRNA.
DR RefSeq; NP_001025470.1; NM_001030299.1.
DR AlphaFoldDB; Q4JIJ2; -.
DR SMR; Q4JIJ2; -.
DR STRING; 9913.ENSBTAP00000012372; -.
DR PaxDb; Q4JIJ2; -.
DR PRIDE; Q4JIJ2; -.
DR GeneID; 507991; -.
DR KEGG; bta:507991; -.
DR CTD; 4552; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; Q4JIJ2; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030586; F:[methionine synthase] reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016723; F:oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor; ISS:UniProtKB.
DR GO; GO:0006306; P:DNA methylation; ISS:UniProtKB.
DR GO; GO:0046655; P:folic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
PE 2: Evidence at transcript level;
KW Amino-acid biosynthesis; Cytoplasm; FAD; Flavoprotein; FMN;
KW Methionine biosynthesis; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine.
FT CHAIN 1..695
FT /note="Methionine synthase reductase"
FT /id="PRO_0000409307"
FT DOMAIN 4..147
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 269..531
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 166..245
FT /note="Hinge"
FT /evidence="ECO:0000250"
FT BINDING 10..14
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 93..124
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 289
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 449..452
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 485..488
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 608..609
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 622..624
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 657
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 695
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBK8"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBK8"
SQ SEQUENCE 695 AA; 77163 MW; A57274B75EC57E0C CRC64;
MRRFLLLYAT QRGQAKAIAE EISEKAVTYG FSADLHCISE SDKYDLKTET APLVMVVSTT
GNGDPPDTAR KFVKAIKDKT LPPDFLAHLR YGLLGLGDSE YTYFCNGGKV IDKRLQELGA
QRFYDTGHAD DCVGLELVVE PWINGLWAAL EKHFLSNRGR EDTSETLTMA SHASRDAVTP
ELLHVESQVG LLKLDDSGGK AAKVLEQNAV NSNQSSTLIV DFEASLTHSV PPLSQASLNI
PSLPPEYLEV HLEEALGQEE SHASVSLVDP VFHVPVSKAV QLTTNDAIKT TLLIELDISK
TDFSYQPGDA FNVICPNSDS EVQFLLQRLQ LADRREHHVA VTIKADTRKK GAALPQHVPE
RCSLQFLLTW CLEIRAVPKK AFLRALADHT GDSAERRRLQ ELCSRQGAAD YTRFVREAGA
CLSDLLRAFP SCQPPLGLLL EHLPKLQPRP YSCASSSLFH PGKLHFIFNI VEFLSNTTEV
ILRRGVCTGW LATLVESILQ PYMCANHVDG KKALAPKISI SPRTTNSFHL PDDPSVPIIM
VGPGAGVAPF IGFLQHREKL QEQHPGGHFG ATWLFFGCRH KERDYLFRDE LRHFLKCGVL
THLEVSFSRD VAVGEEEGPA KYVQDSLQRH SKQVAGVLLQ DSGYVYVCGD AKNMAKDVHD
ALVEIISRET GVEKLEAMKT LATLKEEKRY LQDIW
