dfr1

UniProt ID: P36591
Organism: Schizosaccharomyces pombe 972h-
Review Status: DRAFT
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Gene Description

dfr1 (SPCC1223.08c; UniProt P36591) encodes dihydrofolate reductase (EC 1.5.1.3) fused at its N-terminus to an FSH1-like alpha/beta serine hydrolase domain. The DHFR domain reduces dihydrofolate to tetrahydrofolate with NADPH, completing de novo THF synthesis and regenerating THF after thymidylate synthesis. The cDNA confers trimethoprim resistance in E. coli and methotrexate resistance in yeasts. The fused FSH-like domain may have lysophospholipase activity, by analogy with S. cerevisiae Fsh1, but this is untested. The protein is cytosolic in a genome-wide screen.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004146 dihydrofolate reductase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT inference; consistent.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0004146 dihydrofolate reductase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: EC/ARBA mapping; consistent.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0004146 dihydrofolate reductase activity
IGI
PMID:8088538
The isolation and characterization of the gene (dfr1) encodi... 		ACCEPT
Summary: The dfr1 cDNA confers trimethoprim resistance in E. coli and works in both yeasts.
Supporting Evidence:
PMID:8088538
A sequence encoding dihydrofolate reductase (DHFR) was isolated from a Schizosaccharomyces pombe cDNA library by selecting for trimethoprim resistance in Escherichia coli.
PMID:8088538
The sequence was found to be functional in both Saccharomyces cerevisiae and Sz. pombe.
GO:0004622 phosphatidylcholine lysophospholipase A1 activity
TAS
PMID:32920715
FSH1 encodes lysophospholipase activity in Saccharomyces cer... 		KEEP AS NON CORE
Summary: TAS based on S. cerevisiae Fsh1, a serine hydrolase with lysophospholipase activity. S. pombe dfr1 carries an N-terminal FSH1-like domain fused to DHFR, so a hydrolase activity is plausible. The substrate is untested; Fsh1 prefers lysophosphatidylserine rather than lysophosphatidylcholine.
Supporting Evidence:
PMID:32920715
the purified recombinant protein Fsh1p was identified as a lysophospholipase that specifically acts on lysophosphatidylserine (LPS)
file:SCHPO/dfr1/dfr1-uniprot.txt
DR Pfam; PF03959; FSH1; 1.
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: PAINT inference of mitochondrion from animal DHFR; dfr1 is cytosolic in the screen.
Reason: Not established.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0005829 cytosol
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ... 		ACCEPT
Summary: ORFeome YFP screen placed dfr1 in the cytosol, consistent with a soluble metabolic enzyme.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0046452 dihydrofolate metabolic process
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: PAINT inference; broad.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0046654 tetrahydrofolate biosynthetic process
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT inference; DHFR reduces dihydrofolate to tetrahydrofolate.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0046654 tetrahydrofolate biosynthetic process
IEA
GO_REF:0000120 		ACCEPT
Summary: InterPro mapping; consistent.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0046655 folic acid metabolic process
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Broad parent.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0050661 NADP binding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: NADPH cosubstrate; subsidiary.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
GO:0050661 NADP binding
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: As above.
Supporting Evidence:
file:SCHPO/dfr1/dfr1-uniprot.txt
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +

Core Functions

Cytosolic NADPH-dependent dihydrofolate reductase domain (DHF -> THF).

Molecular Function:
dihydrofolate reductase activity
Directly Involved In:
tetrahydrofolate biosynthetic process
Cellular Locations:
cytosol
Supporting Evidence:
  • PMID:8088538
    A sequence encoding dihydrofolate reductase (DHFR) was isolated from a Schizosaccharomyces pombe cDNA library by selecting for trimethoprim resistance in Escherichia coli.
  • PMID:8088538
    The sequence was found to be functional in both Saccharomyces cerevisiae and Sz. pombe.
  • file:SCHPO/dfr1/dfr1-uniprot.txt
    Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
  • PMID:16823372
    we determined the localization of 4,431 proteins

References

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Suggested Questions for Experts

Q: Does the N-terminal FSH1-like domain of S. pombe dfr1 have lysophospholipase activity, and is there any functional coupling between it and the DHFR domain?

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