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P27653 (C1TC_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
Synonyms:Mthfd
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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.

Subcellular location

Cytoplasm 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

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

nucleotide metabolic process

Inferred from expression pattern PubMed 14597174. Source: RGD

one-carbon metabolic process

Inferred from expression pattern PubMed 14597174. Source: RGD

purine nucleotide biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

tetrahydrofolate interconversion

Inferred from electronic annotation. Source: UniProtKB-UniPathway

tetrahydrofolate metabolic process

Traceable author statement Ref.1. Source: RGD

   Cellular_componentcytoplasm

Traceable author statement Ref.1. Source: RGD

cytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

   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

methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity

Traceable author statement Ref.1. Source: RGD

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_0000199323
Initiator methionine11Removed; alternate By similarity
Chain2 – 935934C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed HAMAP-Rule MF_01543
PRO_0000423283

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

Sequences

Sequence LengthMass (Da)Tools
P27653 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 6E42A56C10A4059E

FASTA935100,996
        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 

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References

[1]"Rat C1-tetrahydrofolate synthase. cDNA isolation, tissue-specific levels of the mRNA, and expression of the protein in yeast."
Thigpen A.E., West M.G., Appling D.R.
J. Biol. Chem. 265:7907-7913(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]Appling D.R.
Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 19 AND 24.
[3]Lubec G., Afjehi-Sadat L.
Submitted (NOV-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 521-532, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: Sprague-Dawley.
Tissue: Spinal cord.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05519 mRNA. Translation: AAA74248.1.
U31032 Genomic DNA. Translation: AAA74744.1.
PIRA35367.
RefSeqNP_071953.1. NM_022508.1.
UniGeneRn.1114.

3D structure databases

ProteinModelPortalP27653.
SMRP27653. Positions 2-296, 469-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP27653. 1 interaction.
MINTMINT-4565955.

Proteomic databases

PaxDbP27653.
PRIDEP27653.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID64300.
KEGGrno:64300.
UCSCRGD:708531. rat.

Organism-specific databases

CTD4522.
RGD708531. Mthfd1.

Phylogenomic databases

eggNOGCOG0190.
HOGENOMHOG000040280.
HOVERGENHBG004916.
InParanoidP27653.
KOK00288.
PhylomeDBP27653.

Enzyme and pathway databases

UniPathwayUPA00193.

Gene expression databases

GenevestigatorP27653.

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

NextBio612926.
PROP27653.

Entry information

Entry nameC1TC_RAT
AccessionPrimary (citable) accession number: P27653
Secondary accession number(s): Q62808
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 112 of the entry and version 3 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