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
	Synonyms:	Mthfd

From

Rattus norvegicus (Rat)

[TaxID: 10116]

Taxonomy

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

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Liver; PubMed=2186031 [NCBI, ExPASy, EBI, Israel, Japan] Thigpen A.E., West M.G., Appling D.R.; "Rat C1-tetrahydrofolate synthase. cDNA isolation, tissue-specific levels of the mRNA, and expression of the protein in yeast."; J. Biol. Chem. 265:7907-7913(1990).
[2]	SEQUENCE REVISION TO 19 AND 24. Appling D.R.; Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
[3]	PROTEIN SEQUENCE OF 521-532, AND MASS SPECTROMETRY. STRAIN=Sprague-Dawley; TISSUE=Spinal cord; Lubec G., Afjehi-Sadat L.; Submitted (NOV-2006) to UniProtKB.

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.
SUBCELLULAR LOCATION: Cytoplasm.
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.
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

J05519; AAA74248.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U31032; AAA74744.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A35367; A35367.

NP_071953.1; -.

3D structure databases

HSSP

P11586; 1A4I. [HSSP ENTRY / PDB]

SMR

P27653; 2-296.

ModBase

P27653.

Organism-specific databases

RGD

708531; Mthfd1.

Gene expression databases

ArrayExpress

P27653; -.

GermOnline

ENSRNOG00000005602; Rattus norvegicus.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-KW).
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: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: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

P27653.

Genome annotation databases

Ensembl

ENSRNOG00000005602; Rattus norvegicus. [Contig view]

GeneID

64300; -.

KEGG

rno:64300; -.

Phylogenomic databases

HOVERGEN

P27653; -.

Other

NextBio

612926; -.

UniRef

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

Keywords

Amino-acid biosynthesis; ATP-binding; Cytoplasm; Direct protein sequencing; 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_0000199323`
`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 (By similarity).`

Sequence information

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

Molecular weight: 100996 Da [This is the MW of the unprocessed precursor]

CRC64: 6E42A56C10A4059E [This is a checksum on the sequence]

        10         20         30         40         50         60 
MAPAGILNGK VVSAQIRNRL KTQVTQMQEQ VPGFTPGLAI LQVGDRDDSN LYINVKLKAA 

        70         80         90        100        110        120 
QEIGIKATHI KLPRTSTESE VLKYVISLNE DATVHGFIVQ LPLDSENSIN TEAVINAIAP 

       130        140        150        160        170        180 
EKDVDGLTSI NAGKLARGDL KDCFIPCTPK GCLELIKETG VQIAGRHAVV VGRSKIVGAP 

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

       250        260        270        280        290        300 
VPDDTKPNGR KVVGDVAYDE AKEKASFITP VPGGVGPMTV AMLMQSTVES AQRFLKKFKP 

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

       370        380        390        400        410        420 
DRLKHQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LHQNVFACVR QPSQGPTFGI 

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

       490        500        510        520        530        540 
PSVNGVRKFS DIQIRRLRRL GIEKTDPAAL TDDEINRFAR LDIDPETITW QRVLDTNDRF 

       550        560        570        580        590        600 
LRKITIGQAP TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRARLGKMV VASSKKGEPI 

       610        620        630        640        650        660 
SCEDLGVSGA 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 PVVVAMNAFK TDTDTELDLI GRLSREHGAF 

       790        800        810        820        830        840 
DAVKCTHWAE GGQGALALAQ AVQRASQAPS SFQLLYDLKL SVEDKIRIIA QKIYGADDIE 

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

       910        920        930 
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF

P27653 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