Methylenetetrahydrofolate dehydrogenase
     (EC 1.5.1.5)
Methenyltetrahydrofolate cyclohydrolase
     (EC 3.5.4.9)
Formyltetrahydrofolate synthetase
     (EC 6.3.4.3)

Gene name

Name:

Mthfd1

From

Mus musculus (Mouse)

[TaxID: 10090]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[2]	KNOCKOUT. DOI=10.1074/jbc.M409380200; PubMed=15611115 [NCBI, ExPASy, EBI, Israel, Japan] Christensen K.E., Patel H., Kuzmanov U., Mejia N.R., MacKenzie R.E.; "Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria."; J. Biol. Chem. 280:7597-7602(2005).
[3]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-786, AND MASS SPECTROMETRY. TISSUE=Liver; DOI=10.1021/pr0604155; PubMed=17203969 [NCBI, ExPASy, EBI, Israel, Japan] Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R.; "Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry."; J. Proteome Res. 6:250-262(2007).

Comments

CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + NADP⁺ = 5,10-methenyltetrahydrofolate + NADPH.
CATALYTIC ACTIVITY: 5,10-methenyltetrahydrofolate + H₂O = 10-formyltetrahydrofolate.
CATALYTIC ACTIVITY: ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
PATHWAY: One-carbon metabolism; tetrahydrofolate pathway .
SUBUNIT: Homodimer (By similarity).
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
DOMAIN: This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity.
MISCELLANEOUS: Knockout mice have revealed Mthfd1l as a monofunctional enzyme having only formyltetrahydrofolate synthetase activity and lacking methenyl-THF dehydrogenase and cyclohydrolase activities.
SIMILARITY: In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
SIMILARITY: In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

BC008523; AAH08523.1; -; mRNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_620084.1; -.

UniGene

Mm.29584

3D structure databases

HSSP

P11586; 1A4I. [HSSP ENTRY / PDB]

Q922D8; 2-296.

PTM databases

Q922D8; -.

2D gel databases

REPRODUCTION-2DPAGE

Q922D8; -.

Organism-specific databases

MGI

MGI:1342005; Mthfd1.

Gene expression databases

ArrayExpress

Q922D8; -.

GermOnline

ENSMUSG00000021048; Mus musculus.

Ontologies

GO:0005739;	Cellular component: mitochondrion (inferred from direct assay from MGI).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0004329;	Molecular function: formate-tetrahydrofolate ligase activity (inferred from electronic annotation from InterPro).
GO:0016155;	Molecular function: formyltetrahydrofolate dehydrogenase activity (inferred from mutant phenotype from MGI).
GO:0004477;	Molecular function: methenyltetrahydrofolate cyclohydrolase activity (inferred from electronic annotation from EC).
GO:0004488;	Molecular function: methylenetetrahydrofolate dehydrogenase (NADP+) activity (inferred from electronic annotation from EC).
GO:0009396;	Biological process: folic acid and derivative biosynthetic process (inferred from electronic annotation from InterPro).
GO:0000105;	Biological process: histidine biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0006548;	Biological process: histidine catabolic process (inferred from mutant phenotype from MGI).
GO:0009086;	Biological process: methionine biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0006730;	Biological process: one-carbon compound metabolic process (inferred from electronic annotation from UniProtKB-KW).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0006164;	Biological process: purine nucleotide biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR000559; Fmtethyd_synth.
IPR016040; NAD(P)-bd.
IPR000672; THF_DHase/CycOHase.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.50.720; NAD(P)-bd; 1.

Pfam

PF01268; FTHFS; 1.
PF00763; THF_DHG_CYH; 1.
PF02882; THF_DHG_CYH_C; 1.
Pfam graphical view of domain structure.

PRINTS

PR00085; THFDHDRGNASE.

ProDom

PD002300; THFDhg/Cyc_hydro; 1.
[Domain structure / List of seq. sharing at least 1 domain]

PROSITE

PS00721; FTHFS_1; 1.
PS00722; FTHFS_2; 1.
PS00766; THF_DHG_CYH_1; 1.
PS00767; THF_DHG_CYH_2; 1.

ProtoNet

Q922D8.

Genome annotation databases

Ensembl

ENSMUSG00000021048; Mus musculus. [Contig view]

GeneID

108156; -.

KEGG

mmu:108156; -.

Phylogenomic databases

HOVERGEN

Q922D8; -.

Other

NextBio

360186; -.

SOURCE

Mthfd1; Mus musculus.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Amino-acid biosynthesis; ATP-binding; Cytoplasm; Histidine biosynthesis; Hydrolase; Ligase; Methionine biosynthesis; Multifunctional enzyme; NADP; Nucleotide-binding; One-carbon metabolism; Oxidoreductase; Phosphoprotein; Purine biosynthesis.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed (By similarity).`
`CHAIN`	`2 935`	`934`	`C-1-tetrahydrofolate synthase, cytoplasmic.`	`PRO_0000199322`
`NP_BIND`	`172 174`	`3`	`NADP (By similarity).`
`NP_BIND`	`380 387`	`8`	`ATP (By similarity).`
`REGION`	`2 305`	`304`	`Methylenetetrahydrofolate dehydrogenase and cyclohydrolase.`
`REGION`	`52 56`	`5`	`Substrate binding (By similarity).`
`REGION`	`99 101`	`3`	`Substrate binding (By similarity).`
`REGION`	`272 276`	`5`	`Substrate binding (By similarity).`
`REGION`	`306 935`	`630`	`Formyltetrahydrofolate synthetase.`
`BINDING`	`197 197`		`NADP (By similarity).`
`MOD_RES`	`786 786`		`Phosphothreonine.`

Sequence information

Length: 935 AA [This is the length of the unprocessed precursor]

Molecular weight: 101256 Da [This is the MW of the unprocessed precursor]

CRC64: BF563467C0F7D278 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MAPAGILNGK LVSAQIRDRL KNQVTRMQEQ VPGFTPGLAI LQVGDRDDSN LYINVKLKAA 

        70         80         90        100        110        120 
EEIGIKATHI KLPRTSTESE VLKYVISLNE DASVHGFIVQ LPLDSENSIN TEAVINAIAP 

       130        140        150        160        170        180 
EKDVDGLTSV SAGKLARGDL NDCFIPCTPK GCLELIKEAG VQIAGRHAVV VGRSKIVGAP 

       190        200        210        220        230        240 
MHDLLLWNNA TVTTCHSKTA NLDKEVNKGD ILVVATGQPE MVKGEWIKPG AVVIDCGINY 

       250        260        270        280        290        300 
VPDDTKPNGR KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AQRFLQKFKP 

       310        320        330        340        350        360 
GKWTIQYNKL NLKTPVPSDI AISRSCKPKL IGNLAREIGL LTEEVELYGE TKAKVLLSAL 

       370        380        390        400        410        420 
DRLKYQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LRQNVFACVR QPSQGPTFGI 

       430        440        450        460        470        480 
KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARIFHELTQ TDKALFNRLV 

       490        500        510        520        530        540 
PSVNGIRKFS DIQIRRLRRL GIEKTDPTTL TDDEINRFAR LDIDPETITW QRVLDTNDRF 

       550        560        570        580        590        600 
LRKITIGQSP TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRERLGRMV VASSKKGEPI 

       610        620        630        640        650        660 
SCEDLGVSGT LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG 

       670        680        690        700        710        720 
PEGFVVTEAG FGADIGMEKF FNIKCRYSGL QPHVVVLVAT VRALKMHGGG PTVTAGLPLP 

       730        740        750        760        770        780 
KAYTEEDLDL VEKGFSNLRK QIENARMFGV PVVVAVNVFK TDTDAELDLV SRLSREHGAF 

       790        800        810        820        830        840 
DAVKCTHWAE GGQGALALAQ AVQRASQAPS SFQLLYDLKL SIEDKIRIIA QRIYGADDIE 

       850        860        870        880        890        900 
LLPEAQNKAE IYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFVLPIRD IRASVGAGFL 

       910        920        930 
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF

Q922D8 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools