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Table 2 Functional categorization of selected genes

From: RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior

Number

Name

Known description, putative function or ortholog function

B30 up-regulation

 Secondary metabolism

AFUA_3G00840

 

FAD-dependent oxygenase, required for asperfuranone biosynthesis in A. nidulans (afoF) FAD-dependant oxygenase; secreted protein

AFUA_3G12910

hasC

O-methyltransferase GliM-like, orthologous member of the “has” secondary metabolite biosynthetic gene cluster of strain A1163. [67]

AFUA_3G12930

hasE

dimethylallyl tryptophan synthase SirD-like, orthologous member of the “has” secondary metabolite biosynthetic gene cluster of strain A1163. [67]

 Transcriptional control

AFUA_5G06190

steA

sexual development transcription factor, involved in sexual development

AFUA_5G05610

 

putative cell cycle control protein Cwf14/Bud31, ortholog(s) have role in cellular bud site selection

AFUA_1G12940

sakA

MAP kinase SakA, nitrogen sensing, is induced upon carbon and nitrogen starvation [52]

 Transport

AFUA_1G12620

aflT

MFS toxin efflux pump

AFUA_7G04290

 

GapA, putative amino acid transporter

AFUA_8G02200

 

proline permease, putative amino acid transporter

 Stress response

AFUA_5G06520

 

low-temperature viability protein ltv1, ortholog(s) have role in cellular response to oxidative stress, response to osmotic stress

AFUA_5G11230

rasA

RAS small monomeric GTPase RasA, involved in cell wall integrity

 Chaperone and protein folding activity

AFUA_2G02320

 

Hsp70 chaperone (BiP)

AFUA_4G03650

 

ribosome associated DnaJ chaperone Zuotin,

AFUA_8G03930

hscA

Hsp70 chaperone HscA, Yap1-dependent induction in response to hydrogen peroxide; hypoxia induced protein

AFUA_2G16290

 

DnaJ domain protein Mas5, ortholog(s) have endoplasmic reticulum localization

AFUA_4G12360

 

prefoldin subunit 1, has domain(s) with predicted unfolded protein binding activity, role in protein folding and prefoldin complex localization

 Detoxification

AFUA_4G12990

trr1

thioredoxin reductase Trr1/Trr2

AFUA_4G00930

 

CorA family metal ion transporter, Mg transport

AFUA_2G13080

 

Nudix/MutT family protein, ortholog(s) have hydrolase activity

AFUA_1G12620

aflT

MFS toxin efflux pump

 Lipid acid and isoprenoid metabolism

AFUA_8G04080

badA

betaine aldehyde dehydrogenase, involved in glycin betain biosynthesis [45]

AFUA_8G04090

codA

choline oxidase, involved in glycin betain biosynthesis [45]

B30 down-regulation

 Secondary metabolism:

AFUA_1G10380

nrps1

nonribosomal peptide synthase Pes1, essential for fumigaclavine C biosynthesis [47]

AFUA_3G03350

sidE

nonribosomal peptide synthase SidE, involved in production of fumarylalanine [48]

 Transcription

AFUA_1G12332

 

jumonji family transcription factor, has domain(s) with predicted zinc ion binding activity

AFUA_1G13750

 

C2H2 transcription factor Rpn4, proteasomal regulator in S. cervisiae

AFUA_1G15230

 

C6 transcription factor, ortholog(s) have role in conidiophore development, conidium formation, hyphal growth

AFUA_1G16460

 

bZIP transcription factor (LziP), ortholog(s) have role in asexual sporulation, sexual sporulation resulting in formation of a cellular spore

AFUA_2G11780

 

CreA, C2H2 transcription factor

  AFUA_2G13260

medA

MedA, transcriptional regulator of adherence, host cell interactions and virulence; required for wild-type levels of conidiation

  AFUA_2G14110

 

sulfur metabolite repression control protein, ortholog(s) have protein binding, bridging, ubiquitin binding activity

  AFUA_2G14680

flbB

Bzip developmental regulator; role in asexual development, gliotoxin production

  AFUA_2G16230

 

C2H2 finger domain protein, has domain(s) with predicted DNA binding, zinc ion binding activity, role in transcription

  AFUA_2G17220

 

C2H2 transcription factor (AmdX), ortholog(s) have sequence-specific DNA binding activity, role in regulation of transcription

  AFUA_3G02000

 

farB like, C6 transcription factor Ctf1B-like, putatively involved in fatty acid degradation

  AFUA_3G05760

 

C6 transcription factor (Fcr1)

  AFUA_3G06250

 

RNA polymerase II mediator complex component, has domain(s) with predicted RNA polymerase II transcription cofactor activity

  AFUA_3G11250

ace2

C2H2 transcription factor (Swi5), with a role in conidiophore development, pigment production, germination and virulence

  AFUA_3G12940

hasF

C6 transcription factor, orthologous member of the “has” secondary metabolite biosynthetic gene cluster of strain A1163. [67]

  AFUA_4G03960

farA

C6 transcription factor Ctf1A, with a role in beta oxidation of long-chain fatty acids

  AFUA_6G12160

 

C6 transcription factor

 Cell wall

  AFUA_6G06340

gfa1

glucosamine-fructose-6-phosphate transaminase, chitin production

  AFUA_2G01170

gel1

1,3-beta-glucanosyltransferase, biosynthesis of fungal cell wall [91]

  AFUA_2G05340

gel4

1,3-beta-glucanosyltransferase, GPI-anchored to the plasma membrane; cell wall maintanance

 Resistance proteins

  AFUA_1G03200

mfsC

MFS transporter

  AFUA_1G10370

 

MFS multidrug transporter

  AFUA_1G10390

abcB

ABC multidrug transporter

  AFUA_1G13800

 

MFS multidrug transporter

  AFUA_3G02610

 

MFS transporter, has domain(s) with predicted role in transmembrane transport and integral to membrane localization

  AFUA_5G00980

 

MFS multidrug transporter, putative transporter of small solutes

  AFUA_5G02700

 

MFS multidrug transporter, putative transporter of small solutes

  AFUA_7G01790

ssu1

MFS transporter, putative sulphite efflux pump

  AFUA_2G14570

 

zinc/cadmium resistance protein, ortholog(s) have zinc ion transmembrane transporter activity, role in cellular zinc ion homeostasis

  AFUA_6G02220

 

MFS toxin efflux pump

  AFUA_8G02050

 

putative transporter of polysaccharides

 Heat shock, chaperone activity

  AFUA_1G07440

hsp70

molecular chaperone Hsp70

  AFUA_1G06020

 

DnaJ domain protein, has domain(s) with predicted heat shock protein binding, unfolded protein binding activity and role in protein folding

  AFUA_1G11180

hsp78

heat shock protein/chaperonin HSP78

  AFUA_1G15270

 

heat shock protein Hsp98/Hsp104/ClpA, ortholog(s) have cytosol, nuclear envelope localization

  AFUA_3G14540

hsp30

heat shock protein Hsp30/Hsp42, putative 30-kDa heat shock protein

  AFUA_4G12850

clxA

calnexin, ER membrane chaperone involved in folding of glycoproteins directed to the secretory pathway

  AFUA_5G07340

 

DnaJ domain protein Psi, ortholog(s) have cytosol, nucleus localization, involved in protein folding and translational initiation

  AFUA_6G06470

 

heat shock protein Hsp30-like, putative integral plasma membrane heat shock protein

B30 up-regulation and 180 min down-regulation

 Protein/ peptide degradation and modification

  AFUA_5G06060

skpA

sulfur metabolism regulator SkpA, part of SCF ubiquitin ligase complex

  AFUA_1G04040

ubiA

ubiquitin

  AFUA_5G04000

 

protein involved in proteasomal and 4S ribosomal subunit biogenesis

 Peptidases

  AFUA_3G05450

 

glutamate carboxypeptidase

  AFUA_6G04510

 

O-sialoglycoprotein endopeptidase, ortholog(s) have chromatin DNA binding activity and role in positive regulation of transcription from RNA polymerase II promoter

  AFUA_6G07330

 

methionine aminopeptidase, type I, orthologs have functions in protein processing

 Glycosylation

  AFUA_6G12360

 

class I alpha-mannosidase 1A, has domain(s) with predicted calcium ion binding, mannosyl-oligosaccharide 1,2-alpha-mannosidase activity

  AFUA_4G10070

 

class I alpha-mannosidase, has domain(s) with predicted calcium ion binding, mannosyl-oligosaccharide 1,2-alpha-mannosidase activity

  AFUA_1G12630

 

mannosylphosphate transferase (Mnn4), putative phosphorylcholine metabolism

  AFUA_4G10750

 

alpha-1,6-mannosyltransferase subunit, Glycan biosynthesis

  AFUA_5G05740

gmtA

Golgi GDP-mannose transporter, involved in biosynthesis of the cell wall polysaccharide galactomannan

 Phosphorylation

  AFUA_6G12820

mpkB

MAP kinase MpkB, putative mitogen-activated protein kinase

  AFUA_5G11730

 

RIO1 family protein kinase, ortholog(s) have nucleocytoplasmic transporter activity, protein kinase activity, role in maturation of SSU-rRNA

  AFUA_1G12940

sakA

MAP kinase SakA, nitrogen sensing, is induced upon carbon and nitrogen starvation [52]

  AFUA_1G09170

 

protein kinase activator (Mob2), ortholog(s) have kinase binding activity and role in conidiophore development, hyphal growth, regulation of kinase activity

  AFUA_1G16000

 

serine/threonine protein kinase, has domain(s) with predicted ATP binding, protein tyrosine kinase activity and role in protein phosphorylation

  AFUA_2G13680

 

calcium/calmodulin-dependent protein kinase, orthologs have a function in stress response

  AFUA_2G05490

 

HEAT repeat protein, ortholog(s) have deoxyhypusine monooxygenase activity

  AFUA_3G12490

 

protein arginine methyltransferase RmtB, ortholog(s) have histone-arginine N-methyltransferase activity

  AFUA_4G13400

 

glycosyltransferase family 28, ortholog(s) have N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity

  AFUA_5G01740

 

deoxyhypusine synthase, putatively first step in hypusine biosynthesis

180 min down-regulation

 ATP binding (GO:0005524)

  AFUA_1G02570

 

aspartyl-tRNA synthetase, cytoplasmic, aspartyl-tRNA synthetase; calcium downregulated

  AFUA_1G05620

 

phenylalanyl-tRNA synthetase, beta subunit, ortholog(s) have phenylalanine-tRNA ligase activity

  AFUA_1G05800

mkk2

MAP kinase kinase (Mkk2), putative mitogen-activated protein kinase kinase (MAPKK); essential for cell wall integrity signaling; calcium induced

  AFUA_1G09010

 

methionyl-tRNA synthetase, ortholog(s) have cytosol localization

  AFUA_1G10310

 

RNase L inhibitor of the ABC superfamily, ATPase, Rnase L inhibitor, orthologs involved in ribosome protection

  AFUA_1G10630

 

S-adenosylmethionine synthetase, putative S-adenosylmethionine synthetase; involved in methylation processes, biosynthesis of biotin and polyamines

  AFUA_2G02320

 

Hsp70 chaperone (BiP)

  AFUA_2G02590

 

aspartyl-tRNA synthetase Dps1

  AFUA_2G03580

 

phenylalanyl-tRNA synthetase beta chain, ortholog(s) have phenylalanine-tRNA ligase activity

  AFUA_2G04620

bipA

Hsp70 chaperone BiP/Kar2

  AFUA_2G05650

 

cytoplasmic asparaginyl-tRNA synthetase, ortholog(s) have asparagine-tRNA ligase activity, role in asparaginyl-tRNA aminoacylation and cytosol localization

  AFUA_2G06110

 

chromatin remodeling and histone, ortholog(s) have role in chromatin silencing at centromere

  AFUA_2G08670

 

acetyl-CoA carboxylase, ortholog(s) have acetyl-CoA carboxylase activity, biotin carboxylase activity and role in long-chain fatty acid biosynthetic

  AFUA_2G09290

hsp60

antigenic mitochondrial protein HSP60, involved in heat shock response

  AFUA_2G13140

ime2

meiosis induction protein kinase, a serine/threonine protein kinase involved in mycotoxin production and sex. development

  AFUA_2G14030

 

arginyl-tRNA synthetase, ortholog(s) have arginine-tRNA ligase activity, role in arginyl-tRNA aminoacylation and cytosol, mitochondrion localization

  AFUA_3G05430

 

DEAD-box RNA helicase Dhh1/Vad1, ortholog(s) have translation regulator activity, nucleic acid binding activity

  AFUA_3G08650

 

C1 tetrahydrofolate synthase

  AFUA_3G10300

 

putative galactokinase with a role in galactose catabolism

  AFUA_3G10530

 

protein serine/threonine kinase (Ran1), orthologs have negative regulation of transcription/ development-meiosis

  AFUA_3G13030

 

t-complex protein 1, gamma subunit (Cct3), ortholog(s) have unfolded protein binding activity, role in cellular response to drug, protein folding

  AFUA_4G07660

ded1

ATP dependent RNA helicase (Dbp1), ATP-dependent RNA helicase, cell cycle affected in S. pombe

  AFUA_4G08060

 

tetrahydrofolylpolyglutamate synthase (Met7), role in one-carbon metabolic process, regulation of DNA methylation and cytosol, mitochondrion

  AFUA_4G13700

 

threonyl-tRNA synthetase, putative tRNA charging

  AFUA_5G05490

 

seryl-tRNA synthetase,

  AFUA_5G05960

 

serine/threonine protein kinase, involved in salt tolerance in S. cerevisiae

  AFUA_5G07020

 

ribosome biogenesis ABC transporter Arb1

  AFUA_5G09610

 

cysteinyl-tRNA synthetase, putative tRNA charging

  AFUA_5G10550

 

ATP synthase F1, beta subunit, orthologs are required for synthesis of ATP, but are non-essential

  AFUA_6G04730

 

bifunctional purine biosynthetic protein Ade1, ortholog(s) have phosphoribosylamine-glycine ligase activity, phosphoribosylformylglycinamidine cyclo-ligase activity

  AFUA_6G05080

 

ABC transporter, ortholog in S. cerevisiae involved in RNA regulation and maturation

  AFUA_6G06870

 

casein kinase I homolog, ortholog(s) have magnesium ion binding, protein serine/threonine kinase activity

  AFUA_6G07540

 

t-complex protein 1, epsilon subunit, ortholog(s) have chaperonin-containing T-complex localization

  AFUA_6G07640

 

lysyl-tRNA synthetase,

  AFUA_6G12630

 

leucyl-tRNA synthetase, putative tRNA charging

  AFUA_6G12820

mpkB

MAP kinase MpkB, orthologs are regulating carbon utilization

  AFUA_7G05660

 

translation elongation factor eEF-3

 Transcriptional control

  AFUA_2G11780

 

C2H2 transcription factor (CreA) ortholog(s) have carbon catabolite repression

  AFUA_2G13260

medA

transcriptional regulator of adherence, host cell interactions and virulence; required for wild-type levels of conidiation

  AFUA_2G16230

 

C2H2 finger domain protein, putative transcription factor, orthologs have predicted regulation of gluconeogenesis and adherence

  AFUA_2G17220

 

C2H2 transcription factor (AmdX), A. nidulans ortholog involved in regulation of acetamide catabolism; regulates amdS transcription

  AFUA_3G08010

ace1

C2H2 transcription factor (Ace1), involved in cation homeostasis and in response to abiotic stress in A. nidulans

  AFUA_3G10300

 

putative galactokinase ortholog in S. cerevisiae involved in conversion of alpha-D-galactose to galactose-1-phosphate, a key step in galactose catabolism

  AFUA_3G10530

 

protein serine/threonine kinase (Ran1), orthologs have negative regulation of transcription/ development-meiosis

  AFUA_3G11250

ace2

C2H2 transcription factor (Swi5), role in conidiophore development, pigment production, germination and virulence

  AFUA_4G10220

 

homeobox transcription factor (RfeB), ortholog(s) have role in conidiophore development, conidium formation, hyphal growth, regulation nucleotide biosynthesis

  AFUA_4G11480

 

C2H2 finger domain protein, S. cerevisiae ortholog is Zinc-regulated transcription facto

  AFUA_4G12470

cpcA

bZIP transcriptional activator of the cross-pathway control system of amino acid biosynthesis upon starvation

  AFUA_5G06190

steA

putative transcription factor involved in sexual development

  AFUA_6G02110

 

MADS box transcription factor Mcm1, orthologs are involved in cell cycle

 Energy

  AFUA_6G12930

acoA

aconitate hydratase, is essential for energy metabolism, TCA cycle and lysine biosynthesis [59]

 Transmembrane transport GO:0055085

  AFUA_1G05020

 

putative sulfate transporter

  AFUA_2G03860

zrfB

plasma membrane low affinity zinc ion, Low affinity plasma membrane zinc transporter; induced by zinc depletion

  AFUA_2G14570

 

zinc/cadmium resistance protein, ortholog(s) have zinc ion transmembrane transporter activity, role in cellular zinc ion homeostasis

  AFUA_3G12900

hasB

MFS transporter, orthologous member of the “has” secondary metabolite biosynthetic gene cluster of strain A1163. [67]

  AFUA_4G14230

 

MFS transporter, putative transporter of small solutes

  AFUA_4G14670

 

MFS quinate transporter, has domain(s) with predicted substrate-specific transmembrane transporter activity

  AFUA_5G00980

 

MFS multidrug transporter, putative transporter of small solutes

  AFUA_5G02700

 

MFS multidrug transporter, putative multidrug resistant protein

  AFUA_7G01790

ssu1

MFS transporter, putative sulphite efflux pump

  AFUA_7G05220

 

putative mitochondrial carrier protein

  AFUA_7G05420

 

mitochondrial intermembrane space protein Mia40, putatively involved in intermembrane space import

180 min up-regulation

 DNA repair

  AFUA_2G02090

agt

O6-alkylguanine DNA alkyltransferase; role in DNA repair

  AFUA_3G11610

nhp6

nucleosome binding protein, non-histone chromosomal protein ortholog in S. cerevisiae play role in elongation and DNA repair

 Transcription factors

  AFUA_2G15680

 

transcription initiation factor iia small chain, ortholog(s) have TBP-class protein binding, activity involved in preinitiation complex assembly activity

  AFUA_4G03960

farA

C6 transcription factor Ctf1A, role in beta oxidation of long-chain fatty acids

  AFUA_7G06320

 

C6 transcription factor, has domain(s) with predicted DNA binding, sequence-specific DNA binding RNA polymerase II transcription factor activity

 Protein binding, degradation, modification

  AFUA_5G05790

 

ubiquitin ligase subunit HrtA, ring finger protein rbxA, putative E3 ubiquitin-protein ligase; NeddH-associated protein

  AFUA_6G09160

 

ubiquitin conjugating enzyme Ubc8, negatively regulates gluconeogenesis by mediating the ubiquitination of fructose-1,6-bisphosphatase [70]

  AFUA_6G14210

 

ubiquitin conjugating enzyme UbcB, ortholog(s) have ubiquitin-protein ligase activity

  AFUA_1G07470

atg8

autophagic death protein atg8, ribo involved in autophagy, determines the size of the autophagosome, induced upon starvation

 Systemic interaction with the environment

  AFUA_4G00660

 

sensor histidine kinase/response regulator, putative stress sensor

 Nitrilases/ cyanid hydratases

  AFUA_6G13450

 

nitrilase, ortholog(s) have cyanide hydratase activity, nitrilase activity and role in cyanide catabolic process

  AFUA_2G17500

 

cyanide hydratase/nitrilase, ortholog(s) have cyanide hydratase activity, nitrilase activity and role in cyanide catabolic process

 Oxidation-reduction process GO:0055114

  AFUA_2G10960

adh2

putative alcohol dehydrogenase Adh2p, in S. cerevisiae is responsible for catalyzing the initial step in the utilization of ethanol as a carbon source

  AFUA_2G11250

 

aryl-alcohol dehydrogenase Aad14, unknown function

  AFUA_2G15930

 

alcohol dehydrogenase, ortholog in S. pombe role in detoxifying alcohols and related compounds, protecting against environmental stresses

  AFUA_4G12990

trr1

thioredoxin reductase Trr1/Trr2, orthologs play a role in detoxification

 Iron homeostasis [12]

  AFUA_3G03640

mirB

MFS siderochrome iron transporter MirB,

  AFUA_3G03440

mirD

MFS siderophore iron transporter, expression upregulated under low iron condition

  AFUA_7G06060

sit1

siderochrome-iron transporter Sit1,

  AFUA_1G17270

fre2

FRE family ferric-chelate reductase, metalloreductase involved in response to iron starvation; reductive iron assimilation, freB

  AFUA_3G03410

sidH

enoyl-CoA hydratase/isomerase family protein, mevalonyl-CoA hydratase; is essential for (TAFC) biosynthesis

  AFUA_3G03400

sidF

siderophore biosynthesis acetylase AceI, hydroxyornithine transacylase; involved in extracellular siderophore biosynthesis; essential for TAFC biosynthesis

  AFUA_3G03420

sidD

nonribosomal peptide synthase SidD, fusarinine C non-ribosomal peptide synthetase (NRPS) involved in extracellular siderophore biosynthesisthesis

  AFUA_3G03430

sitT

ABC multidrug transporter SitT, involved in siderophore excretion

  AFUA_3G03440

mirD

MFS siderophore iron transporter,

  AFUA_2G07680

sidA

L-ornithine N5-oxygenase SidA, first committed step in siderophore biosynthesis; TAFC and ferricrocin biosynthesis

 Reductive iron assimilation

  AFUA_5G03790

fetC

ferrooxidoreductase Fet3,; reductive iron assimilation, FetC

  AFUA_5G03800

ftrA

high-affinity iron transporter FtrA, reductive iron assimilation, FtrA

 Gluconeogenesis

  AFUA_6G07720

acuF

phosphoenolpyruvate carboxykinase AcuF, essential for gluconeogenesis

  AFUA_4G11310

fbp1

fructose-1,6-bisphosphatase Fbp1, essential for glucenogenesis

  AFUA_6G09160

 

ubiquitin conjugating enzyme Ubc8, n negatively regulates gluconeogenesis by mediating the ubiquitination of fructose-1,6-bisphosphatase [70]

  1. Adjusted categories and curated DEGs from FunCat and GO functional analysis that are refered to in the text. DEGs were manually investigated using the Aspergillus Genome Database, http://www.aspergillusgenome.org/ (ASPGD). The known description, putative function or ortholog function obtained are directly cited from ASPGD, from cited paper or description was obtained from link to S. cerevisiae genome project (http://www.yeastgenome.org/), from Candida Genome Database (http://www.candidagenome.org/), from S. pombe pombase (http://www.pombase.org/) [92], and from Neurospora crassa Sequencing Project Broad Institute of Harvard and MIT (http://www.broadinstitute.org/annotation/genome/neurospora/MultiHome.html)