MTHR_BOVIN
ID MTHR_BOVIN Reviewed; 655 AA.
AC Q5I598;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Methylenetetrahydrofolate reductase {ECO:0000305};
DE EC=1.5.1.20 {ECO:0000250|UniProtKB:P42898};
GN Name=MTHFR;
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 Charest R., Beaudry D., Girard C., Palin M.-F.;
RT "Interactions folic acid-vitamin B12-methionine: effects on liver
RT metabolism and production of dairy cows.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the conversion of 5,10-methylenetetrahydrofolate to
CC 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation
CC to methionine. Represents a key regulatory connection between the
CC folate and methionine cycles. {ECO:0000250|UniProtKB:P42898}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADPH;
CC Xref=Rhea:RHEA:19817, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.20;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19819;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADH;
CC Xref=Rhea:RHEA:19821, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.5.1.20;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19823;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P42898};
CC -!- ACTIVITY REGULATION: Allosterically regulated by S-adenosylmethionine
CC (SAM). {ECO:0000250|UniProtKB:P42898}.
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000250|UniProtKB:P42898}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P42898}.
CC -!- DOMAIN: Contains a serine-rich phosphorylation region at the N-terminal
CC and an eukaryote-only S-adenosylmethionine (SAM)-binding domain at the
CC C-terminal. Through asymmetric homodimerization, the two regions are
CC positioned next to each other and N-terminal phosphorylation increases
CC sensitivity to SAM binding and inhibition.
CC {ECO:0000250|UniProtKB:P42898}.
CC -!- PTM: Phosphorylation of an N-terminal serine-rich phosphorylation
CC region increases sensitivity to S-adenosylmethionine and inhibition.
CC {ECO:0000250|UniProtKB:P42898}.
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; AY854631; AAW39033.1; -; mRNA.
DR RefSeq; NP_001011685.1; NM_001011685.1.
DR AlphaFoldDB; Q5I598; -.
DR SMR; Q5I598; -.
DR STRING; 9913.ENSBTAP00000027586; -.
DR PaxDb; Q5I598; -.
DR PRIDE; Q5I598; -.
DR GeneID; 497032; -.
DR KEGG; bta:497032; -.
DR CTD; 4524; -.
DR eggNOG; KOG0564; Eukaryota.
DR InParanoid; Q5I598; -.
DR OrthoDB; 338303at2759; -.
DR BRENDA; 1.5.1.20; 908.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; ISS:UniProtKB.
DR GO; GO:0106312; F:methylenetetrahydrofolate reductase NADH activity; IEA:RHEA.
DR GO; GO:0106313; F:methylenetetrahydrofolate reductase NADPH activity; IEA:RHEA.
DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; ISS:UniProtKB.
DR CDD; cd00537; MTHFR; 1.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR004621; Fadh2_euk.
DR InterPro; IPR003171; Mehydrof_redctse-like.
DR Pfam; PF02219; MTHFR; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
DR TIGRFAMs; TIGR00677; fadh2_euk; 1.
PE 2: Evidence at transcript level;
KW Allosteric enzyme; FAD; Flavoprotein; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..655
FT /note="Methylenetetrahydrofolate reductase"
FT /id="PRO_0000236275"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 62
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 62..67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 93..94
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 93..94
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 156..158
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 173..174
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 196
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 200..203
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 209
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 216
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 227
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 324
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 455
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 460..463
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 480..484
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 559
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT BINDING 572
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 93
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42898"
SQ SEQUENCE 655 AA; 74485 MW; 8F88D084036BD3A5 CRC64;
MVNEPRGNGS PGPRWEGSSS GSESSRTSSR CSTPGLDPER CERLREKMKR KMDSGDKWFS
LEFFPPRTAQ GAVNLISRFD RMGAGGPLFV DVTWHPAGDP GSDKETSSMV IASTAVNYCG
LETILHMTCC HQSREEITGH LNKAKQLGLK NILALRGDPI GDQWEEEEGG FNYATDLVKH
IRNEFGDYFD VCVAGYPKGH PEGESFEADL KHLKEKVAAG ADFIITQLFF EAETFFRFVK
ACSEIGITCP VLPGIFPIQG YHSLRQLVKL SKLEVPQQIK DVIEPIKDND AAIRNYGIEQ
AVSLCQELLA SGLVPGLHFY TLNREVATIE VLKRLGLWIE DPRRPLPWAL SAHPKRRVED
VRPIFWASRP KSYIYRTQEW DEFPNGRWGN SSSPAFGELK DYYLFYLKSK SPKEELLKMW
GEELTSEESV FQVFAHHLSG EPNQNGYKVT CLPWNDEPLA AETSLMKEEL LRVNRRGILT
INSQPNINGK PSSDPIVGWG PSGGYVFQKA YLEFFTSRET VEALLQVLKK YELRVNYHIV
DVKGENITNA PELQPNAVTW GIFPGREIIQ PTVVDPVSFM FWKDEAFALW IEQWGKLYEE
ESPSRMIIQY IHDNYFLVNL VDNEFPLDNC LWQVVEDTFE LLSRPPQDKR ETEAL
