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Q922D8 (C1TC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-1-tetrahydrofolate synthase, cytoplasmic

Short name=C1-THF synthase

Including the following 3 domains:

  1. Methylenetetrahydrofolate dehydrogenase
    EC=1.5.1.5
  2. Methenyltetrahydrofolate cyclohydrolase
    EC=3.5.4.9
  3. Formyltetrahydrofolate synthetase
    EC=6.3.4.3
Gene names
Name:Mthfd1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length935 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. HAMAP-Rule MF_01543

5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. HAMAP-Rule MF_01543

ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate. HAMAP-Rule MF_01543

Pathway

One-carbon metabolism; tetrahydrofolate interconversion. HAMAP-Rule MF_01543

Subunit structure

Homodimer By similarity. HAMAP-Rule MF_01543

Subcellular location

Cytoplasm By similarity HAMAP-Rule MF_01543.

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. HAMAP-Rule MF_01543

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.5

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 processAmino-acid biosynthesis
Histidine biosynthesis
Methionine biosynthesis
One-carbon metabolism
Purine biosynthesis
   Cellular componentCytoplasm
   LigandATP-binding
NADP
Nucleotide-binding
   Molecular functionHydrolase
Ligase
Oxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processfolic acid-containing compound biosynthetic process

Inferred from electronic annotation. Source: InterPro

histidine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

methionine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

one-carbon metabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

purine nucleotide biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

tetrahydrofolate interconversion

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentcytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitochondrion

Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

formate-tetrahydrofolate ligase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

methenyltetrahydrofolate cyclohydrolase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

methylenetetrahydrofolate dehydrogenase (NADP+) activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 935935C-1-tetrahydrofolate synthase, cytoplasmic HAMAP-Rule MF_01543
PRO_0000199322
Initiator methionine11Removed; alternate By similarity
Chain2 – 935934C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed HAMAP-Rule MF_01543
PRO_0000423281

Regions

Nucleotide binding172 – 1743NADP By similarity
Nucleotide binding380 – 3878ATP By similarity
Region1 – 305305Methylenetetrahydrofolate dehydrogenase and cyclohydrolase HAMAP-Rule MF_01543
Region52 – 565Substrate binding By similarity
Region99 – 1013Substrate binding By similarity
Region272 – 2765Substrate binding By similarity
Region306 – 935630Formyltetrahydrofolate synthetase HAMAP-Rule MF_01543

Sites

Binding site1971NADP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Experimental info

Sequence conflict3651H → Y in AAH08523. Ref.3
Sequence conflict6101A → T in AAH08523. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q922D8 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: 0EB92D58C78DDEB5

FASTA935101,200
        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 
DRLKHQPDGK 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 
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 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 

« Hide

References

« Hide 'large scale' references
[1]"Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase."
Patel H., Christensen K.E., Mejia N., MacKenzie R.E.
Arch. Biochem. Biophys. 403:145-148(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Strain: 129/SvJ.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: NOD.
Tissue: Thymus.
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]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, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[5]"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] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF364579 mRNA. Translation: AAL99692.1.
AF364591 expand/collapse EMBL AC list , AF364580, AF364581, AF364582, AF364583, AF364584, AF364585, AF364586, AF364587, AF364588, AF364589, AF364590 Genomic DNA. Translation: AAL99693.1.
AK088700 mRNA. Translation: BAC40513.1.
BC008523 mRNA. Translation: AAH08523.1.
RefSeqNP_620084.2. NM_138745.2.
UniGeneMm.29584.

3D structure databases

ProteinModelPortalQ922D8.
SMRQ922D8. Positions 2-296, 316-935.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ922D8. 5 interactions.
MINTMINT-1856310.

Chemistry

ChEMBLCHEMBL3137.

PTM databases

PhosphoSiteQ922D8.

2D gel databases

REPRODUCTION-2DPAGEQ922D8.

Proteomic databases

PaxDbQ922D8.
PRIDEQ922D8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048.
GeneID108156.
KEGGmmu:108156.
UCSCuc007nxz.2. mouse.

Organism-specific databases

CTD4522.
MGIMGI:1342005. Mthfd1.

Phylogenomic databases

eggNOGCOG0190.
GeneTreeENSGT00750000117401.
HOVERGENHBG004916.
InParanoidQ8R013.
KOK00288.
OMARIFHERT.
OrthoDBEOG76T9QN.
TreeFamTF300623.

Enzyme and pathway databases

UniPathwayUPA00193.

Gene expression databases

ArrayExpressQ922D8.
BgeeQ922D8.
GenevestigatorQ922D8.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPMF_01543. FTHFS.
MF_01576. THF_DHG_CYH.
InterProIPR000559. Formate_THF_ligase.
IPR020628. Formate_THF_ligase_CS.
IPR016040. NAD(P)-bd_dom.
IPR027417. P-loop_NTPase.
IPR000672. THF_DH/CycHdrlase.
IPR020630. THF_DH/CycHdrlase_cat_dom.
IPR020867. THF_DH/CycHdrlase_CS.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
[Graphical view]
PfamPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSPR00085. THFDHDRGNASE.
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS00721. 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]
ProtoNetSearch...

Other

ChiTaRSMTHFD1. mouse.
NextBio360186.
PROQ922D8.
SOURCESearch...

Entry information

Entry nameC1TC_MOUSE
AccessionPrimary (citable) accession number: Q922D8
Secondary accession number(s): Q8R013
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 105 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot