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protein coding gene - pho1 (SPBP4G3.02) - extracellular acid phosphatase Pho1

Gene summary

Standard name
pho1
Systematic ID
SPBP4G3.02
Product
extracellular acid phosphatase Pho1
Organism
Schizosaccharomyces pombe (fission yeast)
UniProt ID
P08091
ORFeome ID
40/40E01
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome II: 4447506..4449053 forward strand

Annotation

PBO:0002267 - 3.1.3.2

Comment

PBO:0091877 - also see PMID:24493644 for 5' UTR characterization

References:

Disease association

MONDO:0030438 - pontocerebellar hypoplasia, type 16

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MONDO:0008566 - thyroid cancer, nonmedullary, 2

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GO biological process

GO:0016036 - cellular response to phosphate starvation

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GO:0046434 - organophosphate catabolic process

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GO cellular component

GO:0030287 - cell wall-bounded periplasmic space

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GO:0005737 - cytoplasm

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GO:0005576 - extracellular region

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GO:0009277 - fungal-type cell wall

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GO molecular function

GO:0003993 - acid phosphatase activity

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Genome organisation

PBO:0004569 - alternative transcripts, alternative initiation site

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Miscellaneous functional group

PBO:0000068 - cell surface glycoprotein

Modification

MOD:00693 - glycosylated residue

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MOD:00818 - glycosylphosphatidylinositolated residue

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MOD:00006 - N-glycosylated residue

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MOD:00046 - O-phospho-L-serine

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MOD:00047 - O-phospho-L-threonine

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Multi-locus phenotype

FYPO:0002244 - abolished acid phosphatase activity

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Genotypes:

FYPO:0006657 - abolished acid phosphatase activity during cellular response to phosphate starvation

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Genotypes:

FYPO:0008351 - abolished AMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008352 - abolished CMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008350 - abolished GMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008353 - abolished UMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008355 - decreased AMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008356 - decreased CMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008357 - decreased GMP 5'-nucleotidase activity

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Genotypes:

FYPO:0008354 - decreased UMP 5'-nucleotidase activity

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Genotypes:

FYPO:0002243 - increased acid phosphatase activity

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Genotypes:

FYPO:0001357 - normal vegetative cell population growth

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Genotypes:

FYPO:0001310 - normal viability in stationary phase

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Genotypes:

Protein sequence feature

SO:0100011 - cleaved_peptide_region

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SO:0000418 - signal_peptide

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Qualitative gene expression

PomGeneEx:0000019 - protein level decreased

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PomGeneEx:0000018 - protein level increased

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PomGeneEx:0000027 - ribosomal density decreased

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PomGeneEx:0000012 - RNA level decreased

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PomGeneEx:0000011 - RNA level increased

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PomGeneEx:0000014 - RNA present

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Quantitative gene expression

PBO:0006310 - protein level

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PBO:0011963 - RNA level

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Single locus phenotype

FYPO:0002244 - abolished acid phosphatase activity

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Genotypes:

FYPO:0000537 - abolished protein secretion during vegetative growth

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Genotypes:

FYPO:0001045 - decreased acid phosphatase activity

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Genotypes:

FYPO:0001060 - decreased glutamate import during vegetative growth

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Genotypes:

FYPO:0001062 - decreased glutamine import

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Genotypes:

FYPO:0001064 - decreased glycine import

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Genotypes:

FYPO:0000872 - decreased histone H3-K9 methylation during vegetative growth

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Genotypes:

FYPO:0000708 - decreased mating efficiency

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Genotypes:

FYPO:0004413 - decreased phosphatase activity during cellular response to phosphate starvation

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Genotypes:

FYPO:0001911 - decreased protein glycosylation during vegetative growth

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Genotypes:

FYPO:0002909 - decreased protein localization to chromatin during vegetative growth

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Genotypes:

FYPO:0001117 - decreased RNA level during vegetative growth

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Genotypes:

FYPO:0001066 - decreased threonine import

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Genotypes:

FYPO:0001068 - decreased tyrosine import

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Genotypes:

FYPO:0002019 - elongated telomeres during vegetative growth

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Genotypes:

FYPO:0004806 - incomplete cell wall disassembly at cell fusion site

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Genotypes:

FYPO:0002243 - increased acid phosphatase activity

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Genotypes:

FYPO:0000825 - increased RNA level during vegetative growth

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Genotypes:

FYPO:0006013 - large ascus

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Genotypes:

FYPO:0001056 - normal arginine import

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Genotypes:

FYPO:0007154 - normal polyphosphate biosynthesis during cellular response to replete phosphate

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Genotypes:

FYPO:0007153 - normal polyphosphate catabolism during cellular response to phosphate starvation

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Genotypes:

FYPO:0001357 - normal vegetative cell population growth

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Genotypes:

FYPO:0009031 - resistance to bleomycin

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Genotypes:

FYPO:0009079 - resistance to calcofluor and sodium dodecyl sulfate

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Genotypes:

FYPO:0001103 - resistance to hydrogen peroxide

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Genotypes:

FYPO:0002578 - resistance to hydroxyurea

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Genotypes:

FYPO:0001583 - resistance to lithium

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Genotypes:

FYPO:0009043 - resistance to potassium chloride and sodium dodecyl sulfate

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Genotypes:

FYPO:0002767 - resistance to terbinafine

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Genotypes:

FYPO:0004325 - sensitive to 5-fluorouracil

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Genotypes:

FYPO:0007931 - sensitive to egtazic acid

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Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

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Genotypes:

FYPO:0002060 - viable vegetative cell population

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Genotypes:

FYPO:0002177 - viable vegetative cell with normal cell morphology

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Genotypes:

Taxonomic conservation

PBO:0011065 - conserved in eukaryotes

PBO:0011071 - conserved in eukaryotes only

PBO:0011064 - conserved in fungi

PBO:0011069 - conserved in metazoa

PBO:0011070 - conserved in vertebrates

Protein features

IDNameInterPro nameDB name
PF00328His_Phos_2His_Pase_clade-2PFAM
cd07061HP_HAP_likeHis_Pase_clade-2CDD
PS00778HIS_ACID_PHOSPHAT_2Acid_Pase_ASPROSITE_PATTERNS
PS00616HIS_ACID_PHOSPHAT_1Acid_Pase_ASPROSITE_PATTERNS
SSF53254Phosphoglycerate mutase-likeHis_PPase_superfamSUPERFAMILY
G3DSA:3.40.50.1240His_PPase_superfamGENE3D
PTHR20963MULTIPLE INOSITOL POLYPHOSPHATE PHOSPHATASE-RELATEDPANTHER
PIRSF000894Acid_PtaseHistidine_acid_Pase_eukPIRSF

Orthologs

References / Literature

PMID:2381421 - Effects of seven different mutations in the pho1 gene on enzymatic activity, glycosylation and secretion of acid phosphatase in Schizosaccharomyces pombe.
Schwaninger R et al. Mol Gen Genet 1990 May;221(3):403-10
PMID:39105351 - A novel transcription factor Sdr1 involving sulfur depletion response in fission yeast.
Ohtsuka H et al. Genes Cells 2024 Aug;29(8):667-680
PMID:21899677 - Cdc42 regulates multiple membrane traffic events in fission yeast.
Estravís M et al. Traffic 2011 Dec;12(12):1744-58
PMID:25117315 - A potential protective role for thiamine in glucose-driven oxidative stress.
Palabiyik B et al. Genet Mol Res 2014 Jul 25;13(3):5582-93
PMID:24763107 - Absolute proteome and phosphoproteome dynamics during the cell cycle of Schizosaccharomyces pombe (Fission Yeast).
Carpy A et al. Mol Cell Proteomics 2014 Aug;13(8):1925-36
PMID:31276588 - Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination.
Sanchez AM et al. Nucleic Acids Res 2019 Sep 19;47(16):8452-8469
PMID:3447747 - Acid phosphatase deficient mutants of Schizosaccharomyces pombe are defective in tyrosine uptake.
Coddington A et al. Curr Genet 1986;11(2):113-7
PMID:29414789 - A long noncoding (lnc)RNA governs expression of the phosphate transporter Pho84 in fission yeast and has cascading effects on the flanking prt lncRNA and pho1 genes.
Garg A et al. J Biol Chem 2018 Mar 23;293(12):4456-4467
PMID:31626996 - Multiplexed proteome profiling of carbon source perturbations in two yeast species with SL-SP3-TMT.
Paulo JA et al. J Proteomics 2020 Jan 06;210:103531
PMID:26749213 - The AP-2 complex is required for proper temporal and spatial dynamics of endocytic patches in fission yeast.
de León N et al. Mol Microbiol 2016 May;100(3):409-24
PMID:34967420 - Genetic screen for suppression of transcriptional interference reveals fission yeast 14-3-3 protein Rad24 as an antagonist of precocious Pol2 transcription termination.
Garg A et al. Nucleic Acids Res 2022 Jan 25;50(2):803-819
PMID:7969124 - The Srp54 GTPase is essential for protein export in the fission yeast Schizosaccharomyces pombe.
Althoff SM et al. Mol Cell Biol 1994 Dec;14(12):7839-54
PMID:24210919 - Mtr4-like protein coordinates nuclear RNA processing for heterochromatin assembly and for telomere maintenance.
Lee NN et al. Cell 2013 Nov 21;155(5):1061-74
PMID:32282918 - Genetic interactions and transcriptomics implicate fission yeast CTD prolyl isomerase Pin1 as an agent of RNA 3' processing and transcription termination that functions via its effects on CTD phosphatase Ssu72.
Sanchez AM et al. Nucleic Acids Res 2020 May 21;48(9):4811-4826
PMID:33010152 - A genetic screen for suppressors of hyper-repression of the fission yeast PHO regulon by Pol2 CTD mutation T4A implicates inositol 1-pyrophosphates as agonists of precocious lncRNA transcription termination.
Garg A et al. Nucleic Acids Res 2020 Nov 04;48(19):10739-10752
PMID:21169418 - Systematic screen of Schizosaccharomyces pombe deletion collection uncovers parallel evolution of the phosphate signal transduction pathway in yeasts.
Henry TC et al. Eukaryot Cell 2011 Feb;10(2):198-206
PMID:35314193 - Fission yeast Duf89 and Duf8901 are cobalt/nickel-dependent phosphatase-pyrophosphatases that act via a covalent aspartyl-phosphate intermediate.
Sanchez AM et al. J Biol Chem 2022 May;298(5):101851
PMID:20118936 - Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
Lantermann AB et al. Nat Struct Mol Biol 2010 Feb;17(2):251-7
PMID:38899862 - Suppression of inositol pyrophosphate toxicosis and hyper-repression of the fission yeast PHO regulon by loss-of-function mutations in chromatin remodelers Snf22 and Sol1.
Schwer B et al. mBio 2024 Jun 20;:e0125224
PMID:25547512 - Dissection of the PHO pathway in Schizosaccharomyces pombe using epistasis and the alternate repressor adenine.
Estill M et al. Curr Genet 2015 May;61(2):175-83
PMID:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:18622392 - Fission yeast SWI/SNF and RSC complexes show compositional and functional differences from budding yeast.
Monahan BJ et al. Nat Struct Mol Biol 2008 Aug;15(8):873-80
PMID:28218250 - Chromatin remodeller Fun30 Fft3 induces nucleosome disassembly to facilitate RNA polymerase II elongation.
Lee J et al. Nat Commun 2017 Feb 20;8:14527
PMID:33579781 - Transcriptional profiling of fission yeast RNA polymerase II CTD mutants.
Garg A et al. RNA 2021 Feb 12;27(5):560-70
PMID:36002457 - Structural analysis of Red1 as a conserved scaffold of the RNA-targeting MTREC/PAXT complex.
Foucher AE et al. Nat Commun 2022 Aug 24;13(1):4969
PMID:39660919 - Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation.
Innokentev A et al. mBio 2024 Dec 11;:e0299224
PMID:25375137 - Systematic analysis of the role of RNA-binding proteins in the regulation of RNA stability.
Hasan A et al. PLoS Genet 2014 Nov;10(11):e1004684
PMID:31010807 - Structure of Fission Yeast Transcription Factor Pho7 Bound to pho1 Promoter DNA and Effect of Pho7 Mutations on DNA Binding and Phosphate Homeostasis.
Garg A et al. Mol Cell Biol 2019 Jul 01;39(13)
PMID:36478272 - Translation-complex profiling of fission yeast cells reveals dynamic rearrangements of scanning ribosomal subunits upon nutritional stress.
Duncan CDS et al. Nucleic Acids Res 2022 Dec 09;50(22):13011-13025
PMID:33711009 - Structure-function analysis of fission yeast cleavage and polyadenylation factor (CPF) subunit Ppn1 and its interactions with Dis2 and Swd22.
Benjamin B et al. PLoS Genet 2021 Mar;17(3):e1009452
PMID:7499352 - Schizosaccharomyces pombe thiamine pyrophosphokinase is encoded by gene tnr3 and is a regulator of thiamine metabolism, phosphate metabolism, mating, and growth.
Fankhauser H et al. J Biol Chem 1995 Nov 24;270(47):28457-62
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
PMID:39367033 - Quantitative proteomics and phosphoproteomics profiling of meiotic divisions in the fission yeast Schizosaccharomyces pombe.
Sivakova B et al. Sci Rep 2024 Oct 04;14(1):23105
PMID:19933844 - Fission yeast Iec1-ino80-mediated nucleosome eviction regulates nucleotide and phosphate metabolism.
Hogan CJ et al. Mol Cell Biol 2010 Feb;30(3):657-74
PMID:22681890 - Hierarchical modularity and the evolution of genetic interactomes across species.
Ryan CJ et al. Mol Cell 2012 Jun 08;46(5):691-704
PMID:23101633 - Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells.
Marguerat S et al. Cell 2012 Oct 26;151(3):671-83
PMID:24192486 - The conserved Fanconi anemia nuclease Fan1 and the SUMO E3 ligase Pli1 act in two novel Pso2-independent pathways of DNA interstrand crosslink repair in yeast.
Fontebasso Y et al. DNA Repair (Amst) 2013 Dec;12(12):1011-23
PMID:29618061 - Histone deacetylation promotes transcriptional silencing at facultative heterochromatin.
Watts BR et al. Nucleic Acids Res 2018 Jun 20;46(11):5426-5440
PMID:32499400 - Nutrient-dependent control of RNA polymerase II elongation rate regulates specific gene expression programs by alternative polyadenylation.
Yague-Sanz C et al. Genes Dev 2020 Jul 01;34(13-14):883-897
PMID:38940614 - Activities and genetic interactions of fission yeast Aps1, a Nudix-type inositol pyrophosphatase and inorganic polyphosphatase.
Ghosh S et al. mBio 2024 Jun 28;:e0108424
PMID:34389684 - Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1.
Schwer B et al. Proc Natl Acad Sci U S A 2021 Aug 17;118(33)
PMID:35012333 - Cleavage-Polyadenylation Factor Cft1 and SPX Domain Proteins Are Agents of Inositol Pyrophosphate Toxicosis in Fission Yeast.
Schwer B et al. mBio 2022 Feb 22;13(1):e0347621
PMID:37787768 - Broad functional profiling of fission yeast proteins using phenomics and machine learning.
Rodríguez-López M et al. Elife 2023 Oct 03;12
PMID:23231582 - Genome-wide characterization of the phosphate starvation response in Schizosaccharomyces pombe.
Carter-O'Connell I et al. BMC Genomics 2012 Dec 12;13:697
PMID:20473289 - Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe.
Kim DU et al. Nat Biotechnol 2010 Jun;28(6):617-623
PMID:1394510 - Regulation of pho1-encoded acid phosphatase of Schizosaccharomyces pombe by adenine and phosphate.
Schweingruber ME et al. Curr Genet 1992 Oct;22(4):289-92
PMID:1318242 - Synthesis and degradation of polyphosphate in the fission yeast Schizosaccharomyces pombe: mutations in phosphatase genes do not affect polyphosphate metabolism.
Müller J et al. FEMS Microbiol Lett 1992 Apr 15;71(2):151-6
PMID:26670050 - Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1.
Kilchert C et al. Cell Rep 2015 Dec 22;13(11):2504-2515
PMID:22633491 - Mapping N-glycosylation sites across seven evolutionarily distant species reveals a divergent substrate proteome despite a common core machinery.
Zielinska DF et al. Mol Cell 2012 May 25;46(4):542-8
PMID:33823663 - A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans.
Halova L et al. Open Biol 2021 Apr;11(4):200405
PMID:3732265 - Glycosylation and secretion of acid phosphatase in Schizosaccharomyces pombe.
Schweingruber AM et al. Eur J Biochem 1986 Jul 01;158(1):133-40
PMID:40015273 - A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin.
Skribbe M et al. Mol Cell 2025 Feb 19;
PMID:26264592 - RNA polymerase II CTD phospho-sites Ser5 and Ser7 govern phosphate homeostasis in fission yeast.
Schwer B et al. RNA 2015 Oct;21(10):1770-80
PMID:32415063 - Conserved protein Pir2 ARS2 mediates gene repression through cryptic introns in lncRNAs.
Thillainadesan G et al. Nat Commun 2020 May 15;11(1):2412
PMID:40063661 - Fission yeast Caprin protein is required for efficient heterochromatin establishment.
Zhang H et al. PLoS Genet 2025 Mar 10;21(3):e1011620
PMID:9839953 - Differences in in vivo acceptor specificity of two galactosyltransferases, the gmh3+ and gma12+ gene products from Schizosaccharomyces pombe.
Yoko-o T et al. Eur J Biochem 1998 Nov 01;257(3):630-7
PMID:36794724 - Cellular responses to long-term phosphate starvation of fission yeast: Maf1 determines fate choice between quiescence and death associated with aberrant tRNA biogenesis.
Garg A et al. Nucleic Acids Res 2023 Apr 24;51(7):3094-3115
PMID:28811350 - Defining the DNA Binding Site Recognized by the Fission Yeast Zn 2 Cys 6 Transcription Factor Pho7 and Its Role in Phosphate Homeostasis.
Schwer B et al. mBio 2017 Aug 15;8(4)
PMID:7961415 - Cloning, nucleotide sequence, and regulation of Schizosaccharomyces pombe thi4, a thiamine biosynthetic gene.
Zurlinden A et al. J Bacteriol 1994 Nov;176(21):6631-5
PMID:25483073 - Chromosome segregation and organization are targets of 5'-Fluorouracil in eukaryotic cells.
Mojardín L et al. Cell Cycle 2015;14(2):206-18
PMID:32546512 - Inactivation of fission yeast Erh1 de-represses pho1 expression: evidence that Erh1 is a negative regulator of prt lncRNA termination.
Schwer B et al. RNA 2020 Oct;26(10):1334-1344
PMID:23697806 - A genome-wide resource of cell cycle and cell shape genes of fission yeast.
Hayles J et al. Open Biol 2013 May 22;3(5):130053
PMID:16537923 - Sterol regulatory element binding protein is a principal regulator of anaerobic gene expression in fission yeast.
Todd BL et al. Mol Cell Biol 2006 Apr;26(7):2817-31
PMID:20625380 - A genome-wide screen for Schizosaccharomyces pombe deletion mutants that affect telomere length.
Liu NN et al. Cell Res 2010 Aug;20(8):963-5
PMID:25428589 - Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast.
Ard R et al. Nat Commun 2014 Nov 27;5:5576
PMID:3536917 - Identification and characterization of thiamin repressible acid phosphatase in yeast.
Schweingruber ME et al. J Biol Chem 1986 Dec 05;261(34):15877-82
PMID:36882296 - Duf89 abets lncRNA control of fission yeast phosphate homeostasis via its antagonism of precocious lncRNA transcription termination.
Sanchez AM et al. RNA 2023 Jun;29(6):808-825
PMID:35536002 - Activities and Structure-Function Analysis of Fission Yeast Inositol Pyrophosphate (IPP) Kinase-Pyrophosphatase Asp1 and Its Impact on Regulation of pho1 Gene Expression.
Benjamin B et al. mBio 2022 Jun 28;13(3):e0103422
PMID:36779416 - The ecl family gene ecl3+ is induced by phosphate starvation and contributes to sexual differentiation in fission yeast.
Ohtsuka H et al. J Cell Sci 2023 Mar 15;136(6)
PMID:30355770 - RNA polymerase II CTD interactome with 3' processing and termination factors in fission yeast and its impact on phosphate homeostasis.
Sanchez AM et al. Proc Natl Acad Sci U S A 2018 Nov 06;115(45):E10652-E10661
PMID:27984744 - Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs.
Joh RI et al. Mol Cell 2016 Dec 15;64(6):1088-1101
PMID:24493644 - lncRNA recruits RNAi and the exosome to dynamically regulate pho1 expression in response to phosphate levels in fission yeast.
Shah S et al. Genes Dev 2014 Feb 01;28(3):231-44
PMID:38133430 - Genetic suppressor screen identifies Tgp1 (glycerophosphocholine transporter), Kcs1 (IP 6 kinase), and Plc1 (phospholipase C) as determinants of inositol pyrophosphate toxicosis in fission yeast.
Bednor L et al. mBio 2023 Dec 22;:e0306223
PMID:3005272 - Isolation and characterization of the structural gene for secreted acid phosphatase from Schizosaccharomyces pombe.
Elliott S et al. J Biol Chem 1986 Feb 25;261(6):2936-41
PMID:30726745 - Fission Yeast NDR/LATS Kinase Orb6 Regulates Exocytosis via Phosphorylation of the Exocyst Complex.
Tay YD et al. Cell Rep 2019 Feb 05;26(6):1654-1667.e7
PMID:21850271 - Genome-wide screening for genes associated with FK506 sensitivity in fission yeast.
Ma Y et al. PLoS One 2011;6(8):e23422
PMID:28410370 - A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion.
Dudin O et al. PLoS Genet 2017 Apr;13(4):e1006721
PMID:33313903 - Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.
Rubio A et al. Nucleic Acids Res 2021 Jan 11;49(1):383-399
PMID:36408920 - UniProt: the Universal Protein Knowledgebase in 2023.
UniProt Consortium Nucleic Acids Res 2023 Jan 06;51(D1):D523-D531
PMID:4092931 - Cloning and characterization of two genes restoring acid phosphatase activity in pho1- mutants of Schizosaccharomyces pombe.
Maundrell K et al. Gene 1985;39(2-3):223-30
PMID:30212894 - Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6 transcription factor Pho7 and its role in phosphate homeostasis.
Garg A et al. Nucleic Acids Res 2018 Nov 30;46(21):11262-11273
PMID:29432178 - General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4.
Duncan CDS et al. Proc Natl Acad Sci U S A 2018 Feb 20;115(8):E1829-E1838
PMID:12845604 - Genome-wide identification of fungal GPI proteins.
De Groot PW et al. Yeast 2003 Jul 15;20(9):781-96
GO_REF:0000024 - Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.