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Protein

C-1-tetrahydrofolate synthase, cytoplasmic

Gene

Mthfd1

Organism
Mus musculus (Mouse)
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.

Pathwayi: 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)DescriptionActionsGraphical viewLength
Binding sitei197NADPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi172 – 174NADPBy similarity3
Nucleotide bindingi380 – 387ATPBy similarity8

GO - Molecular functioni

GO - Biological processi

  • 10-formyltetrahydrofolate biosynthetic process Source: BHF-UCL
  • heart development Source: BHF-UCL
  • histidine biosynthetic process Source: UniProtKB-KW
  • methionine biosynthetic process Source: MGI
  • methionine metabolic process Source: BHF-UCL
  • neural tube closure Source: BHF-UCL
  • neutrophil homeostasis Source: BHF-UCL
  • one-carbon metabolic process Source: MGI
  • purine nucleotide biosynthetic process Source: BHF-UCL
  • serine family amino acid biosynthetic process Source: MGI
  • serine family amino acid metabolic process Source: BHF-UCL
  • somite development Source: BHF-UCL
  • tetrahydrofolate interconversion Source: BHF-UCL
  • transsulfuration Source: BHF-UCL
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

BRENDAi6.3.4.3. 3474.
ReactomeiR-MMU-196757. Metabolism of folate and pterines.
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1342005. Mthfd1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: GO_Central
  • extracellular exosome Source: MGI
  • membrane Source: MGI
  • mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Knockout mice have revealed Mthfd1l as a monofunctional enzyme having only formyltetrahydrofolate synthetase activity and lacking methenyl-THF dehydrogenase and cyclohydrolase activities.1 Publication

Chemistry databases

ChEMBLiCHEMBL3137.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001993221 – 935C-1-tetrahydrofolate synthase, cytoplasmicAdd BLAST935
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00004232812 – 935C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedAdd BLAST934

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei413PhosphoserineBy similarity1
Modified residuei490PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ922D8.
MaxQBiQ922D8.
PaxDbiQ922D8.
PeptideAtlasiQ922D8.
PRIDEiQ922D8.

2D gel databases

REPRODUCTION-2DPAGEQ922D8.

PTM databases

iPTMnetiQ922D8.
PhosphoSitePlusiQ922D8.
SwissPalmiQ922D8.

Expressioni

Gene expression databases

BgeeiENSMUSG00000021048.
GenevisibleiQ922D8. MM.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi223871. 1 interactor.
IntActiQ922D8. 6 interactors.
MINTiMINT-1856310.
STRINGi10090.ENSMUSP00000021443.

Structurei

3D structure databases

ProteinModelPortaliQ922D8.
SMRiQ922D8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 305Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd BLAST305
Regioni52 – 56Substrate bindingBy similarity5
Regioni99 – 101Substrate bindingBy similarity3
Regioni272 – 276Substrate bindingBy similarity5
Regioni306 – 935Formyltetrahydrofolate synthetaseAdd BLAST630

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

eggNOGiKOG4230. Eukaryota.
COG0190. LUCA.
COG2759. LUCA.
GeneTreeiENSGT00860000133777.
HOVERGENiHBG004916.
InParanoidiQ922D8.
KOiK00288.
OMAiTATESEX.
OrthoDBiEOG091G01BU.
TreeFamiTF300623.

Family and domain databases

CDDicd00477. FTHFS. 1 hit.
Gene3Di3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPiMF_01543. FTHFS. 1 hit.
MF_01576. THF_DHG_CYH. 1 hit.
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.
SUPFAMiSSF51735. SSF51735. 1 hit.
SSF52540. 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.

Q922D8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPAGILNGK LVSAQIRDRL KNQVTRMQEQ VPGFTPGLAI LQVGDRDDSN
60 70 80 90 100
LYINVKLKAA EEIGIKATHI KLPRTSTESE VLKYVISLNE DASVHGFIVQ
110 120 130 140 150
LPLDSENSIN TEAVINAIAP EKDVDGLTSV SAGKLARGDL NDCFIPCTPK
160 170 180 190 200
GCLELIKEAG VQIAGRHAVV VGRSKIVGAP MHDLLLWNNA TVTTCHSKTA
210 220 230 240 250
NLDKEVNKGD ILVVATGQPE MVKGEWIKPG AVVIDCGINY VPDDTKPNGR
260 270 280 290 300
KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AQRFLQKFKP
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
LRQNVFACVR QPSQGPTFGI KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT
460 470 480 490 500
AANNLVAAAI DARIFHELTQ TDKALFNRLV PSVNGIRKFS DIQIRRLRRL
510 520 530 540 550
GIEKTDPTTL TDDEINRFAR LDIDPETITW QRVLDTNDRF LRKITIGQSP
560 570 580 590 600
TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRERLGRMV 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
PVVVAVNVFK TDTDAELDLV SRLSREHGAF DAVKCTHWAE GGQGALALAQ
810 820 830 840 850
AVQRASQAPS SFQLLYDLKL SIEDKIRIIA QRIYGADDIE LLPEAQNKAE
860 870 880 890 900
IYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFVLPIRD IRASVGAGFL
910 920 930
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF
Length:935
Mass (Da):101,200
Last modified:July 27, 2011 - v4
Checksum:i0EB92D58C78DDEB5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti365H → Y in AAH08523 (PubMed:15489334).Curated1
Sequence conflicti610A → T in AAH08523 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF364579 mRNA. Translation: AAL99692.1.
AF364591
, 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.
CCDSiCCDS25990.1.
RefSeqiNP_620084.2. NM_138745.2.
UniGeneiMm.29584.

Genome annotation databases

EnsembliENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048.
GeneIDi108156.
KEGGimmu:108156.
UCSCiuc007nxz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF364579 mRNA. Translation: AAL99692.1.
AF364591
, 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.
CCDSiCCDS25990.1.
RefSeqiNP_620084.2. NM_138745.2.
UniGeneiMm.29584.

3D structure databases

ProteinModelPortaliQ922D8.
SMRiQ922D8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223871. 1 interactor.
IntActiQ922D8. 6 interactors.
MINTiMINT-1856310.
STRINGi10090.ENSMUSP00000021443.

Chemistry databases

ChEMBLiCHEMBL3137.

PTM databases

iPTMnetiQ922D8.
PhosphoSitePlusiQ922D8.
SwissPalmiQ922D8.

2D gel databases

REPRODUCTION-2DPAGEQ922D8.

Proteomic databases

EPDiQ922D8.
MaxQBiQ922D8.
PaxDbiQ922D8.
PeptideAtlasiQ922D8.
PRIDEiQ922D8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048.
GeneIDi108156.
KEGGimmu:108156.
UCSCiuc007nxz.2. mouse.

Organism-specific databases

CTDi4522.
MGIiMGI:1342005. Mthfd1.

Phylogenomic databases

eggNOGiKOG4230. Eukaryota.
COG0190. LUCA.
COG2759. LUCA.
GeneTreeiENSGT00860000133777.
HOVERGENiHBG004916.
InParanoidiQ922D8.
KOiK00288.
OMAiTATESEX.
OrthoDBiEOG091G01BU.
TreeFamiTF300623.

Enzyme and pathway databases

UniPathwayiUPA00193.
BRENDAi6.3.4.3. 3474.
ReactomeiR-MMU-196757. Metabolism of folate and pterines.

Miscellaneous databases

ChiTaRSiMthfd1. mouse.
PROiQ922D8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021048.
GenevisibleiQ922D8. MM.

Family and domain databases

CDDicd00477. FTHFS. 1 hit.
Gene3Di3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPiMF_01543. FTHFS. 1 hit.
MF_01576. THF_DHG_CYH. 1 hit.
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.
SUPFAMiSSF51735. SSF51735. 1 hit.
SSF52540. 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...

Entry informationi

Entry nameiC1TC_MOUSE
AccessioniPrimary (citable) accession number: Q922D8
Secondary accession number(s): Q8R013
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 132 of the entry and version 4 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.