ID D3JL96_TRYCR Unreviewed; 477 AA.
AC D3JL96;
DT 23-MAR-2010, integrated into UniProtKB/TrEMBL.
DT 23-MAR-2010, sequence version 1.
DT 27-MAR-2024, entry version 54.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798};
DE EC=1.5.1.3 {ECO:0000256|ARBA:ARBA00012856};
DE EC=2.1.1.45 {ECO:0000256|ARBA:ARBA00011947};
DE Flags: Fragment;
GN Name=DHFR-TS {ECO:0000313|EMBL:ADB79650.1};
OS Trypanosoma cruzi.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=5693 {ECO:0000313|EMBL:ADB79650.1};
RN [1] {ECO:0000313|EMBL:ADB79650.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=GA Rac 45 {ECO:0000313|EMBL:ADB79650.1};
RX PubMed=23457528;
RA Roellig D.M., Savage M.Y., Fujita A.W., Barnabe C., Tibayrenc M.,
RA Steurer F.J., Yabsley M.J.;
RT "Genetic Variation and Exchange in Trypanosoma cruzi Isolates from the
RT United States.";
RL PLoS ONE 8:E56198-E56198(2013).
CC -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis.
CC Key enzyme in folate metabolism. Catalyzes an essential reaction for de
CC novo glycine and purine synthesis, DNA precursor synthesis, and for the
CC conversion of dUMP to dTMP. {ECO:0000256|ARBA:ARBA00025154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-
CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC EC=2.1.1.45; Evidence={ECO:0000256|ARBA:ARBA00001707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3;
CC Evidence={ECO:0000256|ARBA:ARBA00001315};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC {ECO:0000256|ARBA:ARBA00004903}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC synthase family. {ECO:0000256|ARBA:ARBA00006900}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC reductase family. {ECO:0000256|ARBA:ARBA00010176}.
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DR EMBL; GU212916; ADB79650.1; -; Genomic_DNA.
DR AlphaFoldDB; D3JL96; -.
DR UniPathway; UPA00077; UER00158.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00209; DHFR; 1.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR012262; DHFR-TS.
DR InterPro; IPR017925; DHFR_CS.
DR InterPro; IPR001796; DHFR_dom.
DR InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR InterPro; IPR000398; Thymidylate_synthase.
DR InterPro; IPR020940; Thymidylate_synthase_AS.
DR NCBIfam; TIGR03284; thym_sym; 1.
DR PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1.
DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PIRSF; PIRSF000389; DHFR-TS; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603};
KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW NADP {ECO:0000256|ARBA:ARBA00022857};
KW Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727};
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Transferase {ECO:0000256|ARBA:ARBA00022679}.
FT DOMAIN 5..215
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 386
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:ADB79650.1"
FT NON_TER 477
FT /evidence="ECO:0000313|EMBL:ADB79650.1"
SQ SEQUENCE 477 AA; 53701 MW; 5D68706B06E0D69C CRC64;
LALRAFSLVV AVDEHGGIGD GRSIPWNVPE DMKFFRDVTT KLRGKNVKPS PAKRNAVVMG
RKTWDSIPPK FRPLPGRLNV VLSSTLTTQH LLDGLPDEEK RNSHADSIVA VNGGLEQALQ
LLASPNYTPS IETVYCIGGG SVYAEALRPP CVHLLQAIYR TTIRASESSC SVFFRVPESG
TEAAAGIEWQ RETISEELTS ANGNETKYYF EKLIPRNREE EQYLSLVDRI IREGNVKHDR
TGVGTLSIFG AQMRFSLRNN RLPLLTTKRV FWRGVCEELL WFLRGETYAK KLSDKGVHIW
DDNGSRAFLD SRGLTEYEEM DLGPVYGFQW RHFGAAYTHH DANYDGQGVD QIKAIVETLK
TNPDDRRMLF TAWNPSALPR MALPPCHLLA QFYVSNGELS CMLYQRSCDM GLGVPFNIAS
YALLTILIAK ATGLRPGELV HTLGDAHVYS NHVEPCNEQL KRVPRAFPYL VFRRERE
//
