MTDC_BOVIN
ID MTDC_BOVIN Reviewed; 350 AA.
AC Q0P5C2;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial;
DE Includes:
DE RecName: Full=NAD-dependent methylenetetrahydrofolate dehydrogenase;
DE EC=1.5.1.15 {ECO:0000250|UniProtKB:P18155};
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase;
DE EC=3.5.4.9 {ECO:0000250|UniProtKB:P18155};
DE Flags: Precursor;
GN Name=MTHFD2;
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 [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Placenta;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Although its dehydrogenase activity is NAD-specific, it can
CC also utilize NADP at a reduced efficiency.
CC {ECO:0000250|UniProtKB:P13995}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NAD(+) = 5,10-
CC methenyltetrahydrofolate + NADH; Xref=Rhea:RHEA:22892,
CC ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.5.1.15;
CC Evidence={ECO:0000250|UniProtKB:P18155};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,10-methenyltetrahydrofolate + H2O = (6S)-10-
CC formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:57455; EC=3.5.4.9;
CC Evidence={ECO:0000250|UniProtKB:P18155};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P18155};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P13995}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC -!- MISCELLANEOUS: This NAD-dependent bifunctional enzyme has very
CC different kinetic properties than the larger NADP-dependent
CC trifunctional enzyme and is unique in that it requires formation of an
CC enzyme-magnesium complex to allow binding of NAD. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the tetrahydrofolate
CC dehydrogenase/cyclohydrolase family. {ECO:0000305}.
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DR EMBL; BC120249; AAI20250.1; -; mRNA.
DR RefSeq; NP_001069223.1; NM_001075755.2.
DR AlphaFoldDB; Q0P5C2; -.
DR SMR; Q0P5C2; -.
DR STRING; 9913.ENSBTAP00000006419; -.
DR PaxDb; Q0P5C2; -.
DR PRIDE; Q0P5C2; -.
DR GeneID; 517539; -.
DR KEGG; bta:517539; -.
DR CTD; 10797; -.
DR eggNOG; KOG0089; Eukaryota.
DR HOGENOM; CLU_034045_0_1_1; -.
DR InParanoid; Q0P5C2; -.
DR OrthoDB; 1004679at2759; -.
DR TreeFam; TF323998; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IBA:GO_Central.
DR GO; GO:0004487; F:methylenetetrahydrofolate dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0042301; F:phosphate ion binding; ISS:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR HAMAP; MF_01576; THF_DHG_CYH; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR000672; THF_DH/CycHdrlase.
DR InterPro; IPR020630; THF_DH/CycHdrlase_cat_dom.
DR InterPro; IPR020867; THF_DH/CycHdrlase_CS.
DR InterPro; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom.
DR Pfam; PF00763; THF_DHG_CYH; 1.
DR Pfam; PF02882; THF_DHG_CYH_C; 1.
DR PRINTS; PR00085; THFDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00766; THF_DHG_CYH_1; 1.
DR PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Hydrolase; Isopeptide bond; Magnesium; Mitochondrion;
KW Multifunctional enzyme; NAD; NADP; One-carbon metabolism; Oxidoreductase;
KW Reference proteome; Transit peptide; Ubl conjugation.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 36..350
FT /note="Bifunctional methylenetetrahydrofolate
FT dehydrogenase/cyclohydrolase, mitochondrial"
FT /id="PRO_0000305902"
FT BINDING 84..88
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 131..133
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 200..202
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 233
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 309..313
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT MOD_RES 50
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT CROSSLNK 50
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
SQ SEQUENCE 350 AA; 37767 MW; D71A67DFE1FEE05F CRC64;
MAAASFITSL VTRLLRSAQS GRLHQRPFHL SAVRNEAVVI SGRKLAEQIK QEVRQEVEEW
VASGNKRPHL SVVLVGENPA SQSYVLNKTR AAASVGINSE TILKPASISE EELLNLINKL
NNDDNVDGLL VQLPLPEHID ERKVCNAVSP DKDVDGFHVI NVGRMCLDQC SMLPATPWGV
WEIIKRTGIP TLGKNVVVAG RSKNVGMPIA MLLHTDGAHE RPGGDATVTI SHRYTPKEEL
KKHTALADIV ISAAGIPNLI TADMIKEGAA VIDVGINRIQ DPITAKPKLV GDVDFEGVKK
KAGYITPVPG GVGPMTVAML MKNTIIAAKK VLRLEEQEVL KSKELGVASN
