MTD2L_MOUSE
ID MTD2L_MOUSE Reviewed; 338 AA.
AC D3YZG8;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial {ECO:0000250|UniProtKB:D3ZUA0};
DE AltName: Full=NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein {ECO:0000305|PubMed:24733394};
DE Short=MTHFD2-like {ECO:0000303|PubMed:24733394};
DE Includes:
DE RecName: Full=NAD-dependent methylenetetrahydrofolate dehydrogenase {ECO:0000250|UniProtKB:D3ZUA0};
DE EC=1.5.1.15 {ECO:0000250|UniProtKB:D3ZUA0};
DE EC=1.5.1.5 {ECO:0000250|UniProtKB:D3ZUA0};
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000250|UniProtKB:D3ZUA0};
DE EC=3.5.4.9 {ECO:0000250|UniProtKB:D3ZUA0};
GN Name=Mthfd2l {ECO:0000312|MGI:MGI:1915871};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=24733394; DOI=10.1074/jbc.m114.555573;
RA Shin M., Bryant J.D., Momb J., Appling D.R.;
RT "Mitochondrial MTHFD2L is a dual redox cofactor-specific
RT methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate
RT cyclohydrolase expressed in both adult and embryonic tissues.";
RL J. Biol. Chem. 289:15507-15517(2014).
CC -!- FUNCTION: Bifunctional mitochondrial folate-interconverting enzyme that
CC has both NAD/NADP-dependent methylenetetrahydrofolate dehydrogenase and
CC methenyltetrahydrofolate cyclohydrolase activities.
CC {ECO:0000250|UniProtKB:D3ZUA0}.
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:D3ZUA0};
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:D3ZUA0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = 5,10-
CC methenyltetrahydrofolate + NADPH; Xref=Rhea:RHEA:22812,
CC ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.5;
CC Evidence={ECO:0000250|UniProtKB:D3ZUA0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:D3ZUA0};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000250|UniProtKB:D3ZUA0}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:D3ZUA0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:D3ZUA0}; Matrix side
CC {ECO:0000250|UniProtKB:D3ZUA0}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:24733394}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all embryonic days examined in the
CC neural tube and the forebrain, midbrain, and hindbrain. Also detected
CC in the branchial arches and limb buds, particularly along the progress
CC zone. Expression is low at E8.5 but increases at E10.5.
CC {ECO:0000269|PubMed:24733394}.
CC -!- SIMILARITY: Belongs to the tetrahydrofolate
CC dehydrogenase/cyclohydrolase family. {ECO:0000305}.
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DR EMBL; AC109311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC157938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466617; EDL05299.1; -; Genomic_DNA.
DR CCDS; CCDS39145.1; -.
DR RefSeq; NP_081064.1; NM_026788.1.
DR AlphaFoldDB; D3YZG8; -.
DR SMR; D3YZG8; -.
DR BioGRID; 577420; 2.
DR STRING; 10090.ENSMUSP00000071578; -.
DR PhosphoSitePlus; D3YZG8; -.
DR EPD; D3YZG8; -.
DR MaxQB; D3YZG8; -.
DR PaxDb; D3YZG8; -.
DR PeptideAtlas; D3YZG8; -.
DR PRIDE; D3YZG8; -.
DR ProteomicsDB; 291429; -.
DR Antibodypedia; 24601; 152 antibodies from 27 providers.
DR Ensembl; ENSMUST00000071652; ENSMUSP00000071578; ENSMUSG00000029376.
DR GeneID; 665563; -.
DR KEGG; mmu:665563; -.
DR UCSC; uc008ybp.2; mouse.
DR CTD; 441024; -.
DR MGI; MGI:1915871; Mthfd2l.
DR VEuPathDB; HostDB:ENSMUSG00000029376; -.
DR eggNOG; KOG0089; Eukaryota.
DR GeneTree; ENSGT00940000160901; -.
DR HOGENOM; CLU_034045_0_1_1; -.
DR InParanoid; D3YZG8; -.
DR OMA; CKVITAE; -.
DR OrthoDB; 1004679at2759; -.
DR PhylomeDB; D3YZG8; -.
DR TreeFam; TF323998; -.
DR BRENDA; 1.5.1.5; 3474.
DR Reactome; R-MMU-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00193; -.
DR BioGRID-ORCS; 665563; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Mthfd2l; mouse.
DR PRO; PR:D3YZG8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; D3YZG8; protein.
DR Bgee; ENSMUSG00000029376; Expressed in ventricular zone and 214 other tissues.
DR ExpressionAtlas; D3YZG8; baseline and differential.
DR Genevisible; D3YZG8; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; ISS:UniProtKB.
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:0009256; P:10-formyltetrahydrofolate metabolic process; ISO:MGI.
DR GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; ISS:UniProtKB.
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; PS00767; THF_DHG_CYH_2; 1.
PE 2: Evidence at transcript level;
KW Amino-acid biosynthesis; Histidine biosynthesis; Hydrolase; Magnesium;
KW Membrane; Methionine biosynthesis; Mitochondrion;
KW Mitochondrion inner membrane; Multifunctional enzyme; NAD;
KW One-carbon metabolism; Oxidoreductase; Purine biosynthesis;
KW Reference proteome.
FT CHAIN 1..338
FT /note="Bifunctional methylenetetrahydrofolate
FT dehydrogenase/cyclohydrolase 2, mitochondrial"
FT /id="PRO_0000413328"
FT BINDING 89..93
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 136..138
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 205..207
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 238
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P13995"
FT BINDING 314..318
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13995"
SQ SEQUENCE 338 AA; 36438 MW; 71A447A15C918D8E CRC64;
MATRARGFSL LRGRLGRGPV RAPGVAERAW RGFGSSGRRH EAVIISGTNM AKQIQKEIQQ
GVESWIALGN RRPHLSIILV GDNPASHTYV RNKIKAASAV GICSELIIKP KNVSQEELLD
ITDQLNMDPR VSGILVQLPL PDHVDERTIC NGIAPEKDVD GFHIINIGRL CLDQHSLIPA
TASAVWEIIK RAGIETFGKN VVVAGRSKNV GMPIAMLLHT DGEHERPGGD ATVTIAHRYT
PREQLKAHTQ LADIIIVAAG IPRLITADMV REGAAVIDVG INYIQDPVTG KTKLVGDVDF
EAVKKKASFI TPVPGGVGPM TVAMLLKNTL LAAKNIAY
