LAEA_ASPFU
ID LAEA_ASPFU Reviewed; 373 AA.
AC Q4WRY5; Q6TFC7;
DT 16-MAR-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Secondary metabolism regulator laeA {ECO:0000305};
DE AltName: Full=Methyltransferase laeA {ECO:0000305};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:C8VQG9};
DE AltName: Full=Velvet complex subunit laeA {ECO:0000305};
GN Name=laeA {ECO:0000303|PubMed:15075281}; ORFNames=AFUA_1G14660;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15075281; DOI=10.1128/ec.3.2.527-535.2004;
RA Bok J.W., Keller N.P.;
RT "LaeA, a regulator of secondary metabolism in Aspergillus spp.";
RL Eukaryot. Cell 3:527-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16151250; DOI=10.1128/ec.4.9.1574-1582.2005;
RA Bok J.W., Balajee S.A., Marr K.A., Andes D., Nielsen K.F., Frisvad J.C.,
RA Keller N.P.;
RT "LaeA, a regulator of morphogenetic fungal virulence factors.";
RL Eukaryot. Cell 4:1574-1582(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17630330; DOI=10.1128/ec.00140-07;
RA Sugui J.A., Pardo J., Chang Y.C., Muellbacher A., Zarember K.A.,
RA Galvez E.M., Brinster L., Zerfas P., Gallin J.I., Simon M.M.,
RA Kwon-Chung K.J.;
RT "Role of laeA in the regulation of alb1, gliP, conidial morphology, and
RT virulence in Aspergillus fumigatus.";
RL Eukaryot. Cell 6:1552-1561(2007).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17432932; DOI=10.1371/journal.ppat.0030050;
RA Perrin R.M., Fedorova N.D., Bok J.W., Cramer R.A., Wortman J.R., Kim H.S.,
RA Nierman W.C., Keller N.P.;
RT "Transcriptional regulation of chemical diversity in Aspergillus fumigatus
RT by LaeA.";
RL PLoS Pathog. 3:E50-E50(2007).
RN [6]
RP FUNCTION.
RX PubMed=19843884; DOI=10.1182/blood-2009-07-231209;
RA Ben-Ami R., Lewis R.E., Leventakos K., Kontoyiannis D.P.;
RT "Aspergillus fumigatus inhibits angiogenesis through the production of
RT gliotoxin and other secondary metabolites.";
RL Blood 114:5393-5399(2009).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19917717; DOI=10.1128/iai.00980-09;
RA Dagenais T.R., Giles S.S., Aimanianda V., Latge J.P., Hull C.M.,
RA Keller N.P.;
RT "Aspergillus fumigatus LaeA-mediated phagocytosis is associated with a
RT decreased hydrophobin layer.";
RL Infect. Immun. 78:823-829(2010).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22492455; DOI=10.1128/aem.07710-11;
RA Lim F.Y., Hou Y., Chen Y., Oh J.H., Lee I., Bugni T.S., Keller N.P.;
RT "Genome-based cluster deletion reveals an endocrocin biosynthetic pathway
RT in Aspergillus fumigatus.";
RL Appl. Environ. Microbiol. 78:4117-4125(2012).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=23022264; DOI=10.1016/j.fgb.2012.09.005;
RA Soukup A.A., Farnoodian M., Berthier E., Keller N.P.;
RT "NosA, a transcription factor important in Aspergillus fumigatus stress and
RT developmental response, rescues the germination defect of a laeA
RT deletion.";
RL Fungal Genet. Biol. 49:857-865(2012).
RN [10]
RP INDUCTION.
RX PubMed=23876797; DOI=10.1099/mic.0.068742-0;
RA Crowley S., Mahony J., Morrissey J.P., van Sinderen D.;
RT "Transcriptomic and morphological profiling of Aspergillus fumigatus Af293
RT in response to antifungal activity produced by Lactobacillus plantarum
RT 16.";
RL Microbiology 159:2014-2024(2013).
RN [11]
RP FUNCTION.
RX PubMed=24116213; DOI=10.1371/journal.pone.0077147;
RA Dhingra S., Lind A.L., Lin H.C., Tang Y., Rokas A., Calvo A.M.;
RT "The fumagillin gene cluster, an example of hundreds of genes under veA
RT control in Aspergillus fumigatus.";
RL PLoS ONE 8:E77147-E77147(2013).
RN [12]
RP FUNCTION.
RX PubMed=24082142; DOI=10.1073/pnas.1313258110;
RA Wiemann P., Guo C.J., Palmer J.M., Sekonyela R., Wang C.C., Keller N.P.;
RT "Prototype of an intertwined secondary-metabolite supercluster.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:17065-17070(2013).
CC -!- FUNCTION: Methyltransferase that performs automethylation (By
CC similarity). No other methyl-accepting substrate has been identified
CC yet (By similarity). Component of the velvet transcription factor
CC complex that acts as a global regulator for secondary metabolite gene
CC expression (PubMed:15075281, PubMed:17630330, PubMed:19843884,
CC PubMed:24082142, PubMed:24116213). Positively controls expression of
CC 20% to 40% of major classes of secondary metabolite biosynthesis genes
CC such as nonribosomal peptide synthetases, polyketide synthases, and
CC P450 monooxygenases (PubMed:17432932). Controls the expression of the
CC gliotoxin gene cluster (PubMed:15075281, PubMed:17630330,
CC PubMed:19843884). Controls the expression of the fumitremorgin,
CC fumagillin, and pseurotin gene clusters, where genes for fumagillin and
CC pseurotin are physically intertwined in a single supercluster
CC (PubMed:24082142). Regulates the biosynthetic genes required for
CC endocrocin production (PubMed:22492455). Secondary metabolites under
CC the transcriptional regulation of laeA are necessary for inhibition of
CC angiogenesis during invasive infection in mice (PubMed:19843884).
CC Controls the expression of cell surface rodA, a hydrophobin that acts
CC as an antiphagocytic molecule (PubMed:19917717). Regulates also the
CC expression of genes involved in conidial biosynthesis
CC (PubMed:16151250). {ECO:0000250|UniProtKB:C8VQG9,
CC ECO:0000269|PubMed:15075281, ECO:0000269|PubMed:16151250,
CC ECO:0000269|PubMed:17432932, ECO:0000269|PubMed:17630330,
CC ECO:0000269|PubMed:19843884, ECO:0000269|PubMed:19917717,
CC ECO:0000269|PubMed:22492455, ECO:0000269|PubMed:24082142,
CC ECO:0000269|PubMed:24116213}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-methionyl-[protein] + S-adenosyl-L-methionine = S-adenosyl-
CC L-homocysteine + S-methyl-L-methionyl-[protein];
CC Xref=Rhea:RHEA:60560, Rhea:RHEA-COMP:12313, Rhea:RHEA-COMP:15592,
CC ChEBI:CHEBI:16044, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:142742; Evidence={ECO:0000250|UniProtKB:C8VQG9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60561;
CC Evidence={ECO:0000250|UniProtKB:C8VQG9};
CC -!- SUBUNIT: Component of the heterotrimeric velvet complex composed of
CC laeA, veA and velB; VeA acting as a bridging protein between laeA and
CC velB (By similarity). {ECO:0000250|UniProtKB:C8VQG9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:C8VQG9}.
CC -!- INDUCTION: Expression is induces in response to antifungal activity
CC produced by Lactobacillus plantarum (PubMed:23876797).
CC {ECO:0000269|PubMed:23876797}.
CC -!- DISRUPTION PHENOTYPE: Reduces the production of the immunotoxin
CC gliotoxin (PubMed:15075281, PubMed:16151250, PubMed:17630330). Reduces
CC the production of endocrocin (PubMed:22492455). Affects transcription
CC of numerous secondary metabolite biosynthesis genes (PubMed:17432932).
CC Decreases spore formation and germination (PubMed:23022264). Reduces
CC virulence in a murine pulmonary infection model through increased
CC phagocytosis by host macrophages (PubMed:16151250, PubMed:19917717).
CC {ECO:0000269|PubMed:15075281, ECO:0000269|PubMed:16151250,
CC ECO:0000269|PubMed:17432932, ECO:0000269|PubMed:17630330,
CC ECO:0000269|PubMed:19917717, ECO:0000269|PubMed:22492455,
CC ECO:0000269|PubMed:23022264}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. LaeA
CC methyltransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAR01218.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY422723; AAR01218.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AAHF01000004; EAL90797.1; -; Genomic_DNA.
DR RefSeq; XP_752835.1; XM_747742.1.
DR AlphaFoldDB; Q4WRY5; -.
DR SMR; Q4WRY5; -.
DR STRING; 746128.CADAFUBP00001391; -.
DR EnsemblFungi; EAL90797; EAL90797; AFUA_1G14660.
DR GeneID; 3509858; -.
DR KEGG; afm:AFUA_1G14660; -.
DR VEuPathDB; FungiDB:Afu1g14660; -.
DR eggNOG; ENOG502QQMC; Eukaryota.
DR HOGENOM; CLU_010595_2_0_1; -.
DR InParanoid; Q4WRY5; -.
DR OMA; KNCDFYA; -.
DR OrthoDB; 1047281at2759; -.
DR PHI-base; PHI:482; -.
DR Proteomes; UP000002530; Chromosome 1.
DR GO; GO:0005634; C:nucleus; ISA:AspGD.
DR GO; GO:0008168; F:methyltransferase activity; IBA:GO_Central.
DR GO; GO:0052067; P:antiphagocytosis; IMP:AspGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1900691; P:positive regulation of gliotoxin biosynthetic process; IMP:AspGD.
DR GO; GO:0043455; P:regulation of secondary metabolic process; IMP:AspGD.
DR GO; GO:1900376; P:regulation of secondary metabolite biosynthetic process; IMP:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IMP:AspGD.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IEA:UniProtKB-KW.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 2: Evidence at transcript level;
KW Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW Sporulation; Transcription; Transcription regulation; Transferase;
KW Virulence.
FT CHAIN 1..373
FT /note="Secondary metabolism regulator laeA"
FT /id="PRO_0000435743"
FT REGION 55..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 373 AA; 42581 MW; 193DF67DB76FB644 CRC64;
MFLNGQGGQR PPMVAFPPLN VRGSISSGFN ALGRSRNNSD AMDIYTITDR GPAAERDPAA
GRWHANGSPS INSTSSKNPD RYPCYQENGR TYHGYRKGIY MLPCDEQEQD RLDIFHKLFT
VARVSDGLIY APHPTNGRFL DLGCGTGIWA IDVANKYPEA FVVGVDLAPI QPPNHPRNCD
FYAPFDFESL WALGEDSWDL IHMQMGSGSV ASWPNLYRRI YSHLRPGAWF EQVEIDFEPR
CDDRSLEGLA IRQWYQLLKQ ATEETMRPVA HNSRETIRNL QEAGFTEIDH QMVGLPLNPW
HEDEHERRVA RWYNLAISES IETMSLAPFS RVFGWPIERI KQIAADVKSE AFNKEIHTYN
ILHIYQARKP LAN
