Reviewed, UniProtKB/Swiss-Prot Q922D8 (C1TC_MOUSE)

Names and origin

Protein names

Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
      Short name=C1-THF synthase
Including the following 3 domains:
    1- Recommended name:
            Methylenetetrahydrofolate dehydrogenase
              EC=1.5.1.5
    2- Recommended name:
            Methenyltetrahydrofolate cyclohydrolase
              EC=3.5.4.9
    3- Recommended name:
            Formyltetrahydrofolate synthetase
              EC=6.3.4.3

Gene names

Name:

Mthfd1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	935 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Subunit structure	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.
Disruption phenotype	Knockout mice have revealed Mthfd1l as a monofunctional enzyme having only formyltetrahydrofolate synthetase activity and lacking methenyl-THF dehydrogenase and cyclohydrolase activities. Ref.3
Sequence similarities	In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family. In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Histidine biosynthesis Methionine biosynthesis One-carbon metabolism Purine biosynthesis
Cellular component	Cytoplasm
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Hydrolase Ligase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	folic acid and derivative biosynthetic process Inferred from electronic annotation. Source: InterPro histidine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW histidine catabolic process Inferred from mutant phenotype. Source: MGI methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Inferred from electronic annotation. Source: EC formyltetrahydrofolate dehydrogenase activity Inferred from mutant phenotype. Source: MGI methenyltetrahydrofolate cyclohydrolase activity Inferred from electronic annotation. Source: EC methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 935	934	C-1-tetrahydrofolate synthase, cytoplasmic		PRO_0000199322
Regions
	Nucleotide binding	172 – 174	3	NADP By similarity
	Nucleotide binding	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
Sites
	Binding site	197	1	NADP By similarity
Amino acid modifications
	Modified residue	553	1	N6-acetyllysine By similarity
	Modified residue	786	1	Phosphothreonine Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q922D8-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: BF563467C0F7D278	FASTA	935	101,256
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-17; 27-56; 59-66; 75-83; 123-134; 138-173; 176-198; 205-223; 251-262; 314-324; 330-352; 355-362; 371-402; 464-473; 488-495; 505-517; 521-532; 543-553; 658-679; 687-702; 706-733; 747-772; 776-784; 805-819; 833-848 AND 855-889, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[3]	"Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria." Christensen K.E., Patel H., Kuzmanov U., Mejia N.R., MacKenzie R.E. J. Biol. Chem. 280:7597-7602(2005) [PubMed: 15611115] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[4]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed: 17203969] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-786, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC008523 mRNA. Translation: AAH08523.1.
IPI	IPI00122862.
UniGene	Mm.29584
3D structure databases
SMR	Q922D8. Positions 2-296, 469-531.
ModBase	Search...
Protein-protein interaction databases
STRING	Q922D8.
PTM databases
PhosphoSite	Q922D8.
2-D gel databases
REPRODUCTION-2DPAGE	Q922D8.
Proteomic databases
PRIDE	Q922D8.
Genome annotation databases
Ensembl	ENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048; Mus musculus. [Genome view]
UCSC	uc007nxz.1. mouse.
Organism-specific databases
MGI	MGI:1342005. Mthfd1.
Phylogenomic databases
HOVERGEN	Q922D8.
InParanoid	Q922D8.
PhylomeDB	Q922D8.
Enzyme and pathway databases
BRENDA	1.5.1.5. 244. 3.5.4.9. 244. 6.3.4.3. 244.
Gene expression databases
ArrayExpress	Q922D8.
Bgee	Q922D8.
Genevestigator	Q922D8.
GermOnline	ENSMUSG00000021048. Mus musculus.
Family and domain databases
InterPro	IPR000559. Formate_THF_ligase. IPR020628. Formate_THF_ligase_CS. IPR016040. NAD(P)-bd_dom. IPR000672. THF_DH/CycHdrlase. IPR020630. THF_DH/CycHdrlase_cat_dom. IPR020867. THF_DH/CycHdrlase_CS. IPR020631. THF_DH/CycHdrlase_NAD-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF01268. FTHFS. 1 hit. PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
PROSITE	PS00721. FTHFS_1. 1 hit. PS00722. FTHFS_2. 1 hit. PS00766. THF_DHG_CYH_1. 1 hit. PS00767. THF_DHG_CYH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	360186.
SOURCE	Search...

Entry information

Entry name

C1TC_MOUSE

Accession

Primary (citable) accession number: Q922D8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 71 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)