Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

C-1-tetrahydrofolate synthase, cytoplasmic

Gene

Mthfd1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH.
5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate.
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.

Pathway: tetrahydrofolate interconversion

This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.
View all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei197 – 1971NADPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi172 – 1743NADPBy similarity
Nucleotide bindingi380 – 3878ATPBy similarity

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • formate-tetrahydrofolate ligase activity Source: RGD
  • methenyltetrahydrofolate cyclohydrolase activity Source: RGD
  • methylenetetrahydrofolate dehydrogenase (NADP+) activity Source: GO_Central
  • methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Ligase, Oxidoreductase

Keywords - Biological processi

Amino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis

Keywords - Ligandi

ATP-binding, NADP, Nucleotide-binding

Enzyme and pathway databases

UniPathwayiUPA00193.

Names & Taxonomyi

Protein namesi
Recommended name:
C-1-tetrahydrofolate synthase, cytoplasmic
Short name:
C1-THF synthase
Cleaved into the following chain:
Including the following 3 domains:
Methylenetetrahydrofolate dehydrogenase (EC:1.5.1.5)
Methenyltetrahydrofolate cyclohydrolase (EC:3.5.4.9)
Formyltetrahydrofolate synthetase (EC:6.3.4.3)
Gene namesi
Name:Mthfd1
Synonyms:Mthfd
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi708531. Mthfd1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 935935C-1-tetrahydrofolate synthase, cytoplasmicPRO_0000199323Add
BLAST
Initiator methioninei1 – 11Removed; alternateBy similarity
Chaini2 – 935934C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedPRO_0000423283Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei318 – 3181PhosphoserineBy similarity
Modified residuei413 – 4131PhosphoserineBy similarity
Modified residuei490 – 4901PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP27653.
PRIDEiP27653.

Expressioni

Gene expression databases

GenevisibleiP27653. RN.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

IntActiP27653. 1 interaction.
MINTiMINT-4565955.
STRINGi10116.ENSRNOP00000008374.

Structurei

3D structure databases

ProteinModelPortaliP27653.
SMRiP27653. Positions 2-296, 469-531.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 305305Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd
BLAST
Regioni52 – 565Substrate bindingBy similarity
Regioni99 – 1013Substrate bindingBy similarity
Regioni272 – 2765Substrate bindingBy similarity
Regioni306 – 935630Formyltetrahydrofolate synthetaseAdd
BLAST

Domaini

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.

Sequence similaritiesi

In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.Curated
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.Curated

Phylogenomic databases

eggNOGiCOG0190.
HOGENOMiHOG000040280.
HOVERGENiHBG004916.
InParanoidiP27653.
KOiK00288.
PhylomeDBiP27653.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPiMF_01543. FTHFS.
MF_01576. THF_DHG_CYH.
InterProiIPR000559. 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]
PfamiPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS00721. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P27653-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPAGILNGK VVSAQIRNRL KTQVTQMQEQ VPGFTPGLAI LQVGDRDDSN
60 70 80 90 100
LYINVKLKAA QEIGIKATHI KLPRTSTESE VLKYVISLNE DATVHGFIVQ
110 120 130 140 150
LPLDSENSIN TEAVINAIAP EKDVDGLTSI NAGKLARGDL KDCFIPCTPK
160 170 180 190 200
GCLELIKETG VQIAGRHAVV VGRSKIVGAP MHDLLLWNNA TVTTCHSKTA
210 220 230 240 250
DLDKEVNKGD ILVVATGQPE MVKGEWIKPG AVVIDCGINY VPDDTKPNGR
260 270 280 290 300
KVVGDVAYDE AKEKASFITP VPGGVGPMTV AMLMQSTVES AQRFLKKFKP
310 320 330 340 350
GKWTIQYNKL NLKTPVPSDI AISRSCKPKL IGNLAREIGL LTEEVELYGE
360 370 380 390 400
TKAKVLLSAL DRLKHQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH
410 420 430 440 450
LHQNVFACVR QPSQGPTFGI KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT
460 470 480 490 500
AANNLVAAAI DARIFHELTQ TDKALFNRLV PSVNGVRKFS DIQIRRLRRL
510 520 530 540 550
GIEKTDPAAL TDDEINRFAR LDIDPETITW QRVLDTNDRF LRKITIGQAP
560 570 580 590 600
TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRARLGKMV VASSKKGEPI
610 620 630 640 650
SCEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII
660 670 680 690 700
ADRIALKLVG PEGFVVTEAG FGADIGMEKF FNIKCRYSGL QPHVVVLVAT
710 720 730 740 750
VRALKMHGGG PTVTAGLPLP KAYTEEDLDL VEKGFSNLRK QIENARMFGV
760 770 780 790 800
PVVVAMNAFK TDTDTELDLI GRLSREHGAF DAVKCTHWAE GGQGALALAQ
810 820 830 840 850
AVQRASQAPS SFQLLYDLKL SVEDKIRIIA QKIYGADDIE LLPEAQNKAE
860 870 880 890 900
IYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFVLPIRD IRASVGAGFL
910 920 930
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF
Length:935
Mass (Da):100,996
Last modified:January 23, 2007 - v3
Checksum:i6E42A56C10A4059E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05519 mRNA. Translation: AAA74248.1.
U31032 Genomic DNA. Translation: AAA74744.1.
PIRiA35367.
RefSeqiNP_071953.1. NM_022508.1.
UniGeneiRn.1114.

Genome annotation databases

GeneIDi64300.
KEGGirno:64300.
UCSCiRGD:708531. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05519 mRNA. Translation: AAA74248.1.
U31032 Genomic DNA. Translation: AAA74744.1.
PIRiA35367.
RefSeqiNP_071953.1. NM_022508.1.
UniGeneiRn.1114.

3D structure databases

ProteinModelPortaliP27653.
SMRiP27653. Positions 2-296, 469-531.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP27653. 1 interaction.
MINTiMINT-4565955.
STRINGi10116.ENSRNOP00000008374.

Proteomic databases

PaxDbiP27653.
PRIDEiP27653.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi64300.
KEGGirno:64300.
UCSCiRGD:708531. rat.

Organism-specific databases

CTDi4522.
RGDi708531. Mthfd1.

Phylogenomic databases

eggNOGiCOG0190.
HOGENOMiHOG000040280.
HOVERGENiHBG004916.
InParanoidiP27653.
KOiK00288.
PhylomeDBiP27653.

Enzyme and pathway databases

UniPathwayiUPA00193.

Miscellaneous databases

NextBioi612926.
PROiP27653.

Gene expression databases

GenevisibleiP27653. RN.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPiMF_01543. FTHFS.
MF_01576. THF_DHG_CYH.
InterProiIPR000559. 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]
PfamiPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS00721. 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]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiC1TC_RAT
AccessioniPrimary (citable) accession number: P27653
Secondary accession number(s): Q62808
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: June 24, 2015
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.