UniProtKB - Q922D8 (C1TC_MOUSE)
C-1-tetrahydrofolate synthase, cytoplasmic
Mthfd1
Functioni
Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate. These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance.
1 PublicationCatalytic activityi
- (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH1 PublicationEC:1.5.1.51 Publication
- EC:3.5.4.9By similarity
- (6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6S)-10-formyltetrahydrofolate + ADP + phosphate1 PublicationEC:6.3.4.31 Publication
: tetrahydrofolate interconversion Pathwayi
This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 56 | By similarity | 1 | |
Binding sitei | 197 | NADPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 172 – 174 | NADPBy similarity | 3 | |
Nucleotide bindingi | 380 – 387 | ATPBy similarity | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- formate-tetrahydrofolate ligase activity Source: BHF-UCL
- methenyltetrahydrofolate cyclohydrolase activity Source: MGI
- methylenetetrahydrofolate dehydrogenase (NAD+) activity Source: BHF-UCL
- methylenetetrahydrofolate dehydrogenase (NADP+) activity Source: GO_Central
- methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity Source: MGI
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
Keywordsi
Molecular function | Hydrolase, Ligase, Multifunctional enzyme, Oxidoreductase |
Biological process | Amino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis |
Ligand | ATP-binding, NADP, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 6.3.4.3, 3474 |
Reactomei | R-MMU-196757, Metabolism of folate and pterines |
UniPathwayi | UPA00193 |
Names & Taxonomyi
Protein namesi | Recommended name: C-1-tetrahydrofolate synthase, cytoplasmic1 PublicationShort name: C1-THF synthase Cleaved into the following chain: Including the following 3 domains: |
Gene namesi | Name:Mthfd1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1342005, Mthfd1 |
VEuPathDBi | HostDB:ENSMUSG00000021048 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: MGI
Mitochondrion
- mitochondrion Source: MGI
Keywords - Cellular componenti
CytoplasmPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000199322 | 1 – 935 | C-1-tetrahydrofolate synthase, cytoplasmicAdd BLAST | 935 | |
Initiator methioninei | Removed; alternateBy similarity | |||
ChainiPRO_0000423281 | 2 – 935 | C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processedAdd BLAST | 934 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 318 | PhosphoserineBy similarity | 1 | |
Modified residuei | 413 | PhosphoserineBy similarity | 1 | |
Modified residuei | 490 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q922D8 |
jPOSTi | Q922D8 |
MaxQBi | Q922D8 |
PaxDbi | Q922D8 |
PeptideAtlasi | Q922D8 |
PRIDEi | Q922D8 |
ProteomicsDBi | 273855 |
2D gel databases
REPRODUCTION-2DPAGEi | Q922D8 |
PTM databases
iPTMneti | Q922D8 |
PhosphoSitePlusi | Q922D8 |
SwissPalmi | Q922D8 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000021048, Expressed in dorsal pancreas and 346 other tissues |
ExpressionAtlasi | Q922D8, baseline and differential |
Genevisiblei | Q922D8, MM |
Interactioni
Subunit structurei
Homodimer.
By similarityProtein-protein interaction databases
BioGRIDi | 223871, 19 interactors |
IntActi | Q922D8, 3 interactors |
MINTi | Q922D8 |
STRINGi | 10090.ENSMUSP00000021443 |
Miscellaneous databases
RNActi | Q922D8, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 291 | Methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase (D/C) domainBy similarityAdd BLAST | 290 | |
Regioni | 52 – 56 | Substrate bindingBy similarity | 5 | |
Regioni | 99 – 101 | Substrate bindingBy similarity | 3 | |
Regioni | 272 – 276 | Substrate bindingBy similarity | 5 | |
Regioni | 310 – 935 | Formyltetrahydrofolate synthetase domainBy similarityAdd BLAST | 626 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG4230, Eukaryota |
GeneTreei | ENSGT00940000154746 |
HOGENOMi | CLU_003601_2_0_1 |
InParanoidi | Q922D8 |
OMAi | KVDTYTK |
OrthoDBi | 690393at2759 |
PhylomeDBi | Q922D8 |
TreeFami | TF300623 |
Family and domain databases
CDDi | cd00477, FTHFS, 1 hit cd01080, NAD_bind_m-THF_DH_Cyclohyd, 1 hit |
Gene3Di | 3.40.50.300, 2 hits |
HAMAPi | MF_01543, FTHFS, 1 hit MF_01576, THF_DHG_CYH, 1 hit |
InterProi | View protein in InterPro IPR000559, Formate_THF_ligase IPR020628, Formate_THF_ligase_CS IPR036291, NAD(P)-bd_dom_sf 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 |
Pfami | View protein in Pfam PF01268, FTHFS, 1 hit PF00763, THF_DHG_CYH, 1 hit PF02882, THF_DHG_CYH_C, 1 hit |
PRINTSi | PR00085, THFDHDRGNASE |
SUPFAMi | SSF51735, SSF51735, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in 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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1W2P733 | A0A1W2P733_MOUSE | C-1-tetrahydrofolate synthase, cyto... | Mthfd1 | 755 | Annotation score: | ||
A0A1W2P7L5 | A0A1W2P7L5_MOUSE | C-1-tetrahydrofolate synthase, cyto... | Mthfd1 | 160 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 365 | H → Y in AAH08523 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 610 | A → T in AAH08523 (PubMed:15489334).Curated | 1 |
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 |
CCDSi | CCDS25990.1 |
RefSeqi | NP_620084.2, NM_138745.2 |
Genome annotation databases
Ensembli | ENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048 |
GeneIDi | 108156 |
KEGGi | mmu:108156 |
UCSCi | uc007nxz.2, mouse |
Similar proteinsi
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 |
CCDSi | CCDS25990.1 |
RefSeqi | NP_620084.2, NM_138745.2 |
3D structure databases
SMRi | Q922D8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 223871, 19 interactors |
IntActi | Q922D8, 3 interactors |
MINTi | Q922D8 |
STRINGi | 10090.ENSMUSP00000021443 |
Chemistry databases
ChEMBLi | CHEMBL3137 |
PTM databases
iPTMneti | Q922D8 |
PhosphoSitePlusi | Q922D8 |
SwissPalmi | Q922D8 |
2D gel databases
REPRODUCTION-2DPAGEi | Q922D8 |
Proteomic databases
EPDi | Q922D8 |
jPOSTi | Q922D8 |
MaxQBi | Q922D8 |
PaxDbi | Q922D8 |
PeptideAtlasi | Q922D8 |
PRIDEi | Q922D8 |
ProteomicsDBi | 273855 |
Protocols and materials databases
Antibodypediai | 52, 169 antibodies from 30 providers |
DNASUi | 108156 |
Genome annotation databases
Ensembli | ENSMUST00000021443; ENSMUSP00000021443; ENSMUSG00000021048 |
GeneIDi | 108156 |
KEGGi | mmu:108156 |
UCSCi | uc007nxz.2, mouse |
Organism-specific databases
CTDi | 4522 |
MGIi | MGI:1342005, Mthfd1 |
VEuPathDBi | HostDB:ENSMUSG00000021048 |
Phylogenomic databases
eggNOGi | KOG4230, Eukaryota |
GeneTreei | ENSGT00940000154746 |
HOGENOMi | CLU_003601_2_0_1 |
InParanoidi | Q922D8 |
OMAi | KVDTYTK |
OrthoDBi | 690393at2759 |
PhylomeDBi | Q922D8 |
TreeFami | TF300623 |
Enzyme and pathway databases
UniPathwayi | UPA00193 |
BRENDAi | 6.3.4.3, 3474 |
Reactomei | R-MMU-196757, Metabolism of folate and pterines |
Miscellaneous databases
BioGRID-ORCSi | 108156, 20 hits in 64 CRISPR screens |
ChiTaRSi | Mthfd1, mouse |
PROi | PR:Q922D8 |
RNActi | Q922D8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000021048, Expressed in dorsal pancreas and 346 other tissues |
ExpressionAtlasi | Q922D8, baseline and differential |
Genevisiblei | Q922D8, MM |
Family and domain databases
CDDi | cd00477, FTHFS, 1 hit cd01080, NAD_bind_m-THF_DH_Cyclohyd, 1 hit |
Gene3Di | 3.40.50.300, 2 hits |
HAMAPi | MF_01543, FTHFS, 1 hit MF_01576, THF_DHG_CYH, 1 hit |
InterProi | View protein in InterPro IPR000559, Formate_THF_ligase IPR020628, Formate_THF_ligase_CS IPR036291, NAD(P)-bd_dom_sf 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 |
Pfami | View protein in Pfam PF01268, FTHFS, 1 hit PF00763, THF_DHG_CYH, 1 hit PF02882, THF_DHG_CYH_C, 1 hit |
PRINTSi | PR00085, THFDHDRGNASE |
SUPFAMi | SSF51735, SSF51735, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | C1TC_MOUSE | |
Accessioni | Q922D8Primary (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: | February 23, 2022 | |
This is version 162 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families