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UniProtKB - P13922 (DRTS_PLAFK)
Protein
Bifunctional dihydrofolate reductase-thymidylate synthase
Gene
N/A
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Status
Functioni
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Miscellaneous
K1 is from a pyrimethamine-resistant strain; FCR3 is a pyrimethamine-sensitive strain.
Catalytic activityi
: tetrahydrofolate biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate. This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 16 | NADP; via amide nitrogen and carbonyl oxygen | 1 | |
Binding sitei | 31 | Substrate; via carbonyl oxygenBy similarity | 1 | |
Binding sitei | 54 | Substrate | 1 | |
Binding sitei | 108 | Substrate | 1 | |
Binding sitei | 144 | NADP; via carbonyl oxygen | 1 | |
Binding sitei | 164 | Substrate; via carbonyl oxygen | 1 | |
Binding sitei | 170 | Substrate | 1 | |
Binding sitei | 185 | SubstrateBy similarity | 1 | |
Binding sitei | 345 | dUMP | 1 | |
Active sitei | 490 | By similarity | 1 | |
Binding sitei | 491 | dUMP | 1 | |
Binding sitei | 521 | dUMP | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 39 – 45 | NADP | 7 | |
Nucleotide bindingi | 106 – 108 | NADP | 3 | |
Nucleotide bindingi | 128 – 130 | NADP | 3 | |
Nucleotide bindingi | 165 – 172 | NADP | 8 | |
Nucleotide bindingi | 509 – 513 | dUMP | 5 | |
Nucleotide bindingi | 551 – 553 | dUMP | 3 |
GO - Molecular functioni
- dihydrofolate reductase activity Source: UniProtKB-EC
- thymidylate synthase activity Source: UniProtKB-EC
GO - Biological processi
- dTMP biosynthetic process Source: InterPro
- methylation Source: UniProtKB-KW
- one-carbon metabolic process Source: UniProtKB-KW
- tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
Keywordsi
Molecular function | Methyltransferase, Multifunctional enzyme, Oxidoreductase, Transferase |
Biological process | Nucleotide biosynthesis, One-carbon metabolism |
Ligand | NADP |
Enzyme and pathway databases
BRENDAi | 1.5.1.3, 4889 2.1.1.45, 4889 |
SABIO-RKi | P13922 |
UniPathwayi | UPA00077;UER00158 |
Protein family/group databases
MoonProti | P13922 |
Names & Taxonomyi
Protein namesi | |
Organismi | Plasmodium falciparum (isolate K1 / Thailand) |
Taxonomic identifieri | 5839 [NCBI] |
Taxonomic lineagei | Eukaryota › Sar › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodiidae › Plasmodium › Plasmodium (Laverania) › |
Pathology & Biotechi
Chemistry databases
ChEMBLi | CHEMBL1939 |
DrugBanki | DB01131, Proguanil DB00205, Pyrimethamine DB01299, Sulfadoxine |
DrugCentrali | P13922 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186349 | 1 – 608 | Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST | 608 |
Proteomic databases
PRIDEi | P13922 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P13922 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P13922 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 10 – 228 | DHFRAdd BLAST | 219 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 14 – 15 | Substrate binding | 2 | |
Regioni | 322 – 608 | Thymidylate synthaseAdd BLAST | 287 |
Sequence similaritiesi
In the N-terminal section; belongs to the dihydrofolate reductase family.Curated
In the C-terminal section; belongs to the thymidylate synthase family.Curated
Family and domain databases
CDDi | cd00209, DHFR, 1 hit cd00351, TS_Pyrimidine_HMase, 1 hit |
Gene3Di | 3.30.572.10, 1 hit 3.40.430.10, 1 hit |
HAMAPi | MF_00008, Thymidy_synth_bact, 1 hit |
InterProi | View protein in InterPro IPR024072, DHFR-like_dom_sf IPR012262, DHFR-TS IPR017925, DHFR_CS IPR001796, DHFR_dom IPR045097, Thymidate_synth/dCMP_Mease IPR023451, Thymidate_synth/dCMP_Mease_dom IPR036926, Thymidate_synth/dCMP_Mease_sf IPR000398, Thymidylate_synthase IPR020940, Thymidylate_synthase_AS |
PANTHERi | PTHR11548, PTHR11548, 1 hit |
Pfami | View protein in Pfam PF00186, DHFR_1, 1 hit PF00303, Thymidylat_synt, 1 hit |
PIRSFi | PIRSF000389, DHFR-TS, 1 hit |
PRINTSi | PR00108, THYMDSNTHASE |
SUPFAMi | SSF53597, SSF53597, 1 hit SSF55831, SSF55831, 1 hit |
TIGRFAMsi | TIGR03284, thym_sym, 1 hit |
PROSITEi | View protein in PROSITE PS00075, DHFR_1, 1 hit PS51330, DHFR_2, 1 hit PS00091, THYMIDYLATE_SYNTHASE, 1 hit |
i Sequence
Sequence statusi: Complete.
P13922-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC
60 70 80 90 100
NSLDMKYFRA VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN
110 120 130 140 150
VVVMGRTNWE SIPKKFKPLS NRINVILSRT LKKEDFDEDV YIINKVEDLI
160 170 180 190 200
VLLGKLNYYK CFIIGGSVVY QEFLEKKLIK KIYFTRINST YECDVFFPEI
210 220 230 240 250
NENEYQIISV SDVYTSNNTT LDFIIYKKTN NKMLNEQNCI KGEEKNNDMP
260 270 280 290 300
LKNDDKDTCH MKKLTEFYKN VDKYKINYEN DDDDEEEDDF VYFNFNKEKE
310 320 330 340 350
EKNKNSIHPN DFQIYNSLKY KYHPEYQYLN IIYDIMMNGN KQSDRTGVGV
360 370 380 390 400
LSKFGYIMKF DLSQYFPLLT TKKLFLRGII EELLWFIRGE TNGNTLLNKN
410 420 430 440 450
VRIWEANGTR EFLDNRKLFH REVNDLGPIY GFQWRHFGAE YTNMYDNYEN
460 470 480 490 500
KGVDQLKNII NLIKNDPTSR RILLCAWNVK DLDQMALPPC HILCQFYVFD
510 520 530 540 550
GKLSCIMYQR SCDLGLGVPF NIASYSIFTH MIAQVCNLQP AQFIHVLGNA
560 570 580 590 600
HVYNNHIDSL KIQLNRIPYP FPTLKLNPDI KNIEDFTISD FTIQNYVHHE
KISMDMAA
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 16 | A → V in strain: Isolate Palo-Alto. | 1 | |
Natural varianti | 51 | N → I. | 1 | |
Natural varianti | 59 | R → C in strain: Isolate FCR-3, Isolate Gambia and Isolate Palo-Alto. | 1 | |
Natural varianti | 108 | N → T in strain: Isolate FCR-3, Isolate Gambia and Isolate Palo-Alto. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M22159 Genomic DNA Translation: AAA29580.1 J04643 Genomic DNA Translation: AAA29586.1 J03772 Genomic DNA Translation: AAB59212.1 J03028 Genomic DNA Translation: AAA29585.1 |
PIRi | A39975, RDZQK1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M22159 Genomic DNA Translation: AAA29580.1 J04643 Genomic DNA Translation: AAA29586.1 J03772 Genomic DNA Translation: AAB59212.1 J03028 Genomic DNA Translation: AAA29585.1 |
PIRi | A39975, RDZQK1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1J3I | X-ray | 2.33 | A/B | 1-280 | [»] | |
C/D | 281-608 | [»] | ||||
1J3J | X-ray | 2.30 | A/B | 1-280 | [»] | |
C/D | 281-608 | [»] | ||||
1J3K | X-ray | 2.10 | A/B | 1-280 | [»] | |
C/D | 281-608 | [»] | ||||
3DG8 | X-ray | 2.58 | A/B | 1-280 | [»] | |
C/D | 281-608 | [»] | ||||
3DGA | X-ray | 2.70 | A/B | 1-280 | [»] | |
C/D | 281-608 | [»] | ||||
SMRi | P13922 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Chemistry databases
BindingDBi | P13922 |
ChEMBLi | CHEMBL1939 |
DrugBanki | DB01131, Proguanil DB00205, Pyrimethamine DB01299, Sulfadoxine |
DrugCentrali | P13922 |
Protein family/group databases
MoonProti | P13922 |
Proteomic databases
PRIDEi | P13922 |
Enzyme and pathway databases
UniPathwayi | UPA00077;UER00158 |
BRENDAi | 1.5.1.3, 4889 2.1.1.45, 4889 |
SABIO-RKi | P13922 |
Miscellaneous databases
EvolutionaryTracei | P13922 |
Family and domain databases
CDDi | cd00209, DHFR, 1 hit cd00351, TS_Pyrimidine_HMase, 1 hit |
Gene3Di | 3.30.572.10, 1 hit 3.40.430.10, 1 hit |
HAMAPi | MF_00008, Thymidy_synth_bact, 1 hit |
InterProi | View protein in InterPro IPR024072, DHFR-like_dom_sf IPR012262, DHFR-TS IPR017925, DHFR_CS IPR001796, DHFR_dom IPR045097, Thymidate_synth/dCMP_Mease IPR023451, Thymidate_synth/dCMP_Mease_dom IPR036926, Thymidate_synth/dCMP_Mease_sf IPR000398, Thymidylate_synthase IPR020940, Thymidylate_synthase_AS |
PANTHERi | PTHR11548, PTHR11548, 1 hit |
Pfami | View protein in Pfam PF00186, DHFR_1, 1 hit PF00303, Thymidylat_synt, 1 hit |
PIRSFi | PIRSF000389, DHFR-TS, 1 hit |
PRINTSi | PR00108, THYMDSNTHASE |
SUPFAMi | SSF53597, SSF53597, 1 hit SSF55831, SSF55831, 1 hit |
TIGRFAMsi | TIGR03284, thym_sym, 1 hit |
PROSITEi | View protein in PROSITE PS00075, DHFR_1, 1 hit PS51330, DHFR_2, 1 hit PS00091, THYMIDYLATE_SYNTHASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DRTS_PLAFK | |
Accessioni | P13922Primary (citable) accession number: P13922 Secondary accession number(s): Q27734 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | August 1, 1990 | |
Last modified: | February 23, 2022 | |
This is version 130 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families