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UniProtKB - O96553 (C1TC_DROME)
Protein
C-1-tetrahydrofolate synthase, cytoplasmic
Gene
pug
Organism
Drosophila melanogaster (Fruit fly)
Status
Functioni
Catalytic activityi
- (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPHBy similarityEC:1.5.1.5By similarity
- EC:3.5.4.9By similarity
- (6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6S)-10-formyltetrahydrofolate + ADP + phosphateBy similarityEC:6.3.4.3By similarity
: tetrahydrofolate interconversion Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 230 | NADPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 205 – 207 | NADPBy similarity | 3 | |
Nucleotide bindingi | 413 – 420 | ATPBy similarity | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- formate-tetrahydrofolate ligase activity Source: UniProtKB
- methenyltetrahydrofolate cyclohydrolase activity Source: GO_Central
- methylenetetrahydrofolate dehydrogenase (NADP+) activity Source: GO_Central
GO - Biological processi
- cellular amino acid biosynthetic process Source: UniProtKB
- histidine biosynthetic process Source: UniProtKB-KW
- methionine biosynthetic process Source: UniProtKB-KW
- purine nucleotide biosynthetic process Source: UniProtKB-KW
- tetrahydrofolate interconversion Source: GO_Central
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
Reactomei | R-DME-196757, Metabolism of folate and pterines |
SignaLinki | O96553 |
UniPathwayi | UPA00193 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:pug ORF Names:CG4067 |
Organismi | Drosophila melanogaster (Fruit fly) |
Taxonomic identifieri | 7227 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora › |
Proteomesi |
|
Organism-specific databases
FlyBasei | FBgn0020385, pug |
VEuPathDBi | VectorBase:FBgn0020385 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000199324 | 1 – 968 | C-1-tetrahydrofolate synthase, cytoplasmicAdd BLAST | 968 |
Proteomic databases
PaxDbi | O96553 |
Expressioni
Tissue specificityi
Present in all tissues.1 Publication
Gene expression databases
Bgeei | FBgn0020385, Expressed in arthropod fat body and 46 other tissues |
ExpressionAtlasi | O96553, baseline and differential |
Genevisiblei | O96553, DM |
Interactioni
Subunit structurei
Homodimer.
By similarityProtein-protein interaction databases
BioGRIDi | 66423, 2 interactors |
IntActi | O96553, 4 interactors |
STRINGi | 7227.FBpp0081741 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 338 | Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd BLAST | 338 | |
Regioni | 86 – 90 | Substrate bindingBy similarity | 5 | |
Regioni | 133 – 135 | Substrate bindingBy similarity | 3 | |
Regioni | 305 – 309 | Substrate bindingBy similarity | 5 | |
Regioni | 339 – 968 | Formyltetrahydrofolate synthetaseAdd BLAST | 630 |
Domaini
This trifunctional enzyme consists of two major domains: a N-terminal part, containing the methylene-THF dehydrogenase and the methenyl-THF cyclohydrolase activities and a larger formyl-THF synthetase domain.
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
eggNOGi | KOG4230, Eukaryota |
GeneTreei | ENSGT00940000167165 |
InParanoidi | O96553 |
PhylomeDBi | O96553 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform B (identifier: O96553-1) [UniParc]FASTAAdd to basket
Also known as: D
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSAQYQRFLK VLEKWPAEKS KVGSGEWTAE PAIKMSGAKI ISGTAVAKSI
60 70 80 90 100
REELRNEVTA MSKQLADFVP GLRIVQVGGR EDSNVYIRMK IKAATEIGID
110 120 130 140 150
AAHVQLPRSI TEVELLDKIN DLNEDPRVHG IIVQMPLDCD TPIDSHRITD
160 170 180 190 200
AVSPEKDVDG LHTVNEGRLA IGDLGGFLPC TPWGCLELIR RSGVEIAGAR
210 220 230 240 250
AVVLGRSKIV GTPAAELLKW ANATVTVCHS KTRNLEEITR SADILVVGIG
260 270 280 290 300
VAEMVKGSWI KPGAVVIDCG INVKPDASKA SGSKLVGDVD YAEALQVAGH
310 320 330 340 350
LTPVPGGVGP MTVAMLMKNT VRSAARFLER LAKSQWALQT LPLKPQRPVP
360 370 380 390 400
SDIVIARAQK PKDIAVLAKE IGLEAREVSL YGNKKAKISL SVLERLKDKE
410 420 430 440 450
VGHYVVVAGM TPTPLGEGKT TTLMGLVQAL GAHKLRNTMA ALRQPSQGPT
460 470 480 490 500
FGIKGGAAGG GYAQVIPMEE FNLHLTGDIH AVSAANNLLA AQLDTRIFHE
510 520 530 540 550
NTQKDKALYD RLVPAIKGQR KFSPIQLRRL QKLGITKTDP DTLTADEYGP
560 570 580 590 600
FARLDIDPDT IMWERVVDIN DRYLRTITVG QSPTEKGISR ETRFSISVAS
610 620 630 640 650
EIMAVLALSR SLEDMKQRLA DMVVAFDKRG KPVTADDLGV TGALAVLLKD
660 670 680 690 700
ALEPNLMQSL EGTPVLVHAG PFANIAHGCN SIIADEVGLK LVGKNGFVCT
710 720 730 740 750
EAGFGSDIGM EKFCNIKCRT SGRKPNAMVL VATVRAIKMH GGGAPVTPGA
760 770 780 790 800
PLNKQYTEEN LELVQKGLPN LLQHIENGKA FGMPVVVSLN AHSADTPAEH
810 820 830 840 850
ELVKKAALEA GAFAAVVSTH WADGGAGAVQ LADAVIKACE QGNQFRLLYD
860 870 880 890 900
LELPLVDKMN KIATTMYGAG KVVLSPAAEE KVKRLTDAGF GNLPICMSKV
910 920 930 940 950
SGSFTGDAKI KGAPKGFTLD VEDVYVSAGA GFVVAMCGEV TKMPGLPTRP
960
AIYDIDLNTE TGEIEGLF
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0B4K623 | A0A0B4K623_DROME | C-1-tetrahydrofolate synthase, cyto... | pug bs14h02.y1, Dmel\CG4067, MTHFD, Pug, pugD | 965 | Annotation score: |
Sequence cautioni
The sequence AAL39291 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 879 | E → K in AAX33426 (Ref. 4) Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010883 | 1 – 34 | Missing in isoform A. 1 PublicationAdd BLAST | 34 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF082097 Genomic DNA Translation: AAC78847.1 AE014297 Genomic DNA Translation: AAG22140.2 AE014297 Genomic DNA Translation: AAN13478.1 AE014297 Genomic DNA Translation: AAN13479.1 AE014297 Genomic DNA Translation: AAX52944.1 BT021278 mRNA Translation: AAX33426.1 AY069146 mRNA Translation: AAL39291.1 Different initiation. |
RefSeqi | NP_001014614.1, NM_001014614.2 [O96553-1] NP_477254.1, NM_057906.4 [O96553-2] NP_731489.2, NM_169350.3 [O96553-1] NP_731490.1, NM_169351.2 [O96553-2] |
Genome annotation databases
EnsemblMetazoai | FBtr0082264; FBpp0081741; FBgn0020385 [O96553-1] FBtr0082265; FBpp0081742; FBgn0020385 [O96553-2] FBtr0082266; FBpp0081743; FBgn0020385 [O96553-2] FBtr0100144; FBpp0099494; FBgn0020385 [O96553-1] |
GeneIDi | 41279 |
KEGGi | dme:Dmel_CG4067 |
UCSCi | CG4067-RA, d. melanogaster [O96553-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF082097 Genomic DNA Translation: AAC78847.1 AE014297 Genomic DNA Translation: AAG22140.2 AE014297 Genomic DNA Translation: AAN13478.1 AE014297 Genomic DNA Translation: AAN13479.1 AE014297 Genomic DNA Translation: AAX52944.1 BT021278 mRNA Translation: AAX33426.1 AY069146 mRNA Translation: AAL39291.1 Different initiation. |
RefSeqi | NP_001014614.1, NM_001014614.2 [O96553-1] NP_477254.1, NM_057906.4 [O96553-2] NP_731489.2, NM_169350.3 [O96553-1] NP_731490.1, NM_169351.2 [O96553-2] |
3D structure databases
SMRi | O96553 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 66423, 2 interactors |
IntActi | O96553, 4 interactors |
STRINGi | 7227.FBpp0081741 |
Proteomic databases
PaxDbi | O96553 |
Protocols and materials databases
DNASUi | 41279 |
Genome annotation databases
EnsemblMetazoai | FBtr0082264; FBpp0081741; FBgn0020385 [O96553-1] FBtr0082265; FBpp0081742; FBgn0020385 [O96553-2] FBtr0082266; FBpp0081743; FBgn0020385 [O96553-2] FBtr0100144; FBpp0099494; FBgn0020385 [O96553-1] |
GeneIDi | 41279 |
KEGGi | dme:Dmel_CG4067 |
UCSCi | CG4067-RA, d. melanogaster [O96553-1] |
Organism-specific databases
CTDi | 41279 |
FlyBasei | FBgn0020385, pug |
VEuPathDBi | VectorBase:FBgn0020385 |
Phylogenomic databases
eggNOGi | KOG4230, Eukaryota |
GeneTreei | ENSGT00940000167165 |
InParanoidi | O96553 |
PhylomeDBi | O96553 |
Enzyme and pathway databases
UniPathwayi | UPA00193 |
Reactomei | R-DME-196757, Metabolism of folate and pterines |
SignaLinki | O96553 |
Miscellaneous databases
BioGRID-ORCSi | 41279, 0 hits in 3 CRISPR screens |
GenomeRNAii | 41279 |
PROi | PR:O96553 |
Gene expression databases
Bgeei | FBgn0020385, Expressed in arthropod fat body and 46 other tissues |
ExpressionAtlasi | O96553, baseline and differential |
Genevisiblei | O96553, DM |
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_DROME | |
Accessioni | O96553Primary (citable) accession number: O96553 Secondary accession number(s): A4V2N7 Q8T0P2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 19, 2003 |
Last sequence update: | July 19, 2004 | |
Last modified: | February 23, 2022 | |
This is version 164 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Drosophila annotation project |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Drosophila
Drosophila: entries, gene names and cross-references to FlyBase - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families