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LAEA_EMENI
ID   LAEA_EMENI              Reviewed;         374 AA.
AC   C8VQG9; Q5BF73;
DT   16-MAR-2016, integrated into UniProtKB/Swiss-Prot.
DT   03-NOV-2009, sequence version 1.
DT   03-AUG-2022, entry version 63.
DE   RecName: Full=Protein-methionine methyltransferase laeA {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000269|PubMed:23532849};
DE   AltName: Full=Secondary metabolism regulator laeA {ECO:0000305};
DE   AltName: Full=Velvet complex subunit laeA {ECO:0000305};
GN   Name=laeA {ECO:0000303|PubMed:15075281}; ORFNames=ANIA_00807;
OS   Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS   M139) (Aspergillus nidulans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=227321;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=16372000; DOI=10.1038/nature04341;
RA   Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA   Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA   Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA   Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA   Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA   Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA   Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA   Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA   Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT   "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT   fumigatus and A. oryzae.";
RL   Nature 438:1105-1115(2005).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA   Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA   Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA   Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA   Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA   Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA   Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA   Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA   van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA   Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA   Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA   Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA   Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA   Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA   van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA   Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA   Oliver S.G., Turner G.;
RT   "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT   effort.";
RL   Fungal Genet. Biol. 46:S2-13(2009).
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RC   STRAIN=TJH3.40;
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   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16968230; DOI=10.1111/j.1365-2958.2006.05330.x;
RA   Bok J.W., Noordermeer D., Kale S.P., Keller N.P.;
RT   "Secondary metabolic gene cluster silencing in Aspergillus nidulans.";
RL   Mol. Microbiol. 61:1636-1645(2006).
RN   [5]
RP   INDUCTION.
RX   PubMed=18378656; DOI=10.1128/aem.02842-07;
RA   Atoui A., Bao D., Kaur N., Grayburn W.S., Calvo A.M.;
RT   "Aspergillus nidulans natural product biosynthesis is regulated by mpkB, a
RT   putative pheromone response mitogen-activated protein kinase.";
RL   Appl. Environ. Microbiol. 74:3596-3600(2008).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE VELVET COMPLEX,
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=18556559; DOI=10.1126/science.1155888;
RA   Bayram O., Krappmann S., Ni M., Bok J.W., Helmstaedt K., Valerius O.,
RA   Braus-Stromeyer S., Kwon N.J., Keller N.P., Yu J.H., Braus G.H.;
RT   "VelB/VeA/LaeA complex coordinates light signal with fungal development and
RT   secondary metabolism.";
RL   Science 320:1504-1506(2008).
RN   [7]
RP   FUNCTION.
RX   PubMed=20132440; DOI=10.1111/j.1365-2958.2010.07051.x;
RA   Reyes-Dominguez Y., Bok J.W., Berger H., Shwab E.K., Basheer A.,
RA   Gallmetzer A., Scazzocchio C., Keller N., Strauss J.;
RT   "Heterochromatic marks are associated with the repression of secondary
RT   metabolism clusters in Aspergillus nidulans.";
RL   Mol. Microbiol. 76:1376-1386(2010).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=21152013; DOI=10.1371/journal.pgen.1001226;
RA   Sarikaya Bayram O., Bayram O., Valerius O., Park H.S., Irniger S.,
RA   Gerke J., Ni M., Han K.H., Yu J.H., Braus G.H.;
RT   "LaeA control of velvet family regulatory proteins for light-dependent
RT   development and fungal cell-type specificity.";
RL   PLoS Genet. 6:E1001226-E1001226(2010).
RN   [9]
RP   IDENTIFICATION IN THE VELVET COMPLEX.
RX   PubMed=23065618; DOI=10.1007/978-1-62703-122-6_14;
RA   Bayram O., Bayram O.S., Valerius O., Joehnk B., Braus G.H.;
RT   "Identification of protein complexes from filamentous fungi with tandem
RT   affinity purification.";
RL   Methods Mol. Biol. 944:191-205(2012).
RN   [10]
RP   S-ADENOSYL METHIONINE-BINDING.
RX   PubMed=23341778; DOI=10.1371/journal.pgen.1003193;
RA   Palmer J.M., Theisen J.M., Duran R.M., Grayburn W.S., Calvo A.M.,
RA   Keller N.P.;
RT   "Secondary metabolism and development is mediated by LlmF control of VeA
RT   subcellular localization in Aspergillus nidulans.";
RL   PLoS Genet. 9:E1003193-E1003193(2013).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF MET-207, AND METHYLATION AT
RP   MET-207.
RX   PubMed=23532849; DOI=10.1074/jbc.m113.465765;
RA   Patananan A.N., Palmer J.M., Garvey G.S., Keller N.P., Clarke S.G.;
RT   "A novel automethylation reaction in the Aspergillus nidulans LaeA protein
RT   generates S-methylmethionine.";
RL   J. Biol. Chem. 288:14032-14045(2013).
RN   [12]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX   PubMed=24023705; DOI=10.1371/journal.pone.0074951;
RA   Caballero Ortiz S., Trienens M., Rohlfs M.;
RT   "Induced fungal resistance to insect grazing: reciprocal fitness
RT   consequences and fungal gene expression in the Drosophila-Aspergillus model
RT   system.";
RL   PLoS ONE 8:E74951-E74951(2013).
CC   -!- FUNCTION: Methyltransferase that performs automethylation at Met-207
CC       (PubMed:23532849). No other methyl-accepting substrate has been
CC       identified yet (PubMed:23532849). Component of the velvet transcription
CC       factor complex that acts as a global regulator for secondary metabolite
CC       gene expression (PubMed:15075281, PubMed:20132440). Controls the
CC       expression of the sterigmatocystin, penicillin, and lovastatin gene
CC       clusters (PubMed:15075281, PubMed:16968230). Controls light-dependent
CC       formation of the velB-vosA complex, veA protein modification, and is
CC       required for light-mediated inhibition of sexual development
CC       (PubMed:21152013). Within the velvet complex, controls light-dependent
CC       secondary metabolism (PubMed:18556559). Involved in the defense
CC       response against Drosophila melanogaster larval grazing
CC       (PubMed:24023705). {ECO:0000269|PubMed:15075281,
CC       ECO:0000269|PubMed:16968230, ECO:0000269|PubMed:18556559,
CC       ECO:0000269|PubMed:20132440, ECO:0000269|PubMed:21152013,
CC       ECO:0000269|PubMed:24023705}.
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:0000269|PubMed:23532849};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60561;
CC         Evidence={ECO:0000269|PubMed:23532849};
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 (PubMed:18556559). VeA acts as a bridging protein between laeA and
CC       velB (PubMed:18556559). {ECO:0000269|PubMed:18556559}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18556559}.
CC   -!- INDUCTION: Expression is negatively regulated by the transcription
CC       factor AflR, as well as by two signal transduction elements, protein
CC       kinase A and rasA. Expression is up-regulated in D.melanogaster-
CC       challenged colonies in a Drosophila-Aspergillus insect-fungus model
CC       system (PubMed:24023705). Expression is also controled by mpkB
CC       (PubMed:18378656). {ECO:0000269|PubMed:15075281,
CC       ECO:0000269|PubMed:18378656, ECO:0000269|PubMed:24023705}.
CC   -!- PTM: Self-methylates at Met-207. {ECO:0000269|PubMed:23532849}.
CC   -!- DISRUPTION PHENOTYPE: Reduces secondary metabolite production,
CC       including sterigmatocystin, a carcinogen biochemically related to the
CC       agricultural contaminant aflatoxin. Results in constitutive sexual
CC       differentiation (PubMed:21152013). Impairs defense response against
CC       D.melanogaster larval grazing (PubMed:24023705).
CC       {ECO:0000269|PubMed:15075281, ECO:0000269|PubMed:16968230,
CC       ECO:0000269|PubMed:21152013, ECO:0000269|PubMed:24023705}.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily. LaeA
CC       methyltransferase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=EAA65637.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AACD01000013; EAA65637.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BN001308; CBF88745.1; -; Genomic_DNA.
DR   RefSeq; XP_658411.1; XM_653319.1.
DR   AlphaFoldDB; C8VQG9; -.
DR   SMR; C8VQG9; -.
DR   STRING; 162425.CADANIAP00001854; -.
DR   EnsemblFungi; CBF88745; CBF88745; ANIA_00807.
DR   EnsemblFungi; EAA65637; EAA65637; AN0807.2.
DR   GeneID; 2876583; -.
DR   KEGG; ani:AN0807.2; -.
DR   VEuPathDB; FungiDB:AN0807; -.
DR   eggNOG; ENOG502QQMC; Eukaryota.
DR   HOGENOM; CLU_010595_2_0_1; -.
DR   InParanoid; C8VQG9; -.
DR   OMA; KNCDFYA; -.
DR   OrthoDB; 1047281at2759; -.
DR   Proteomes; UP000000560; Chromosome VIII.
DR   Proteomes; UP000005890; Unassembled WGS sequence.
DR   GO; GO:0005634; C:nucleus; IDA:AspGD.
DR   GO; GO:0008168; F:methyltransferase activity; IDA:AspGD.
DR   GO; GO:0030437; P:ascospore formation; IMP:AspGD.
DR   GO; GO:0051701; P:biological process involved in interaction with host; IMP:AspGD.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0042316; P:penicillin metabolic process; IMP:AspGD.
DR   GO; GO:0075296; P:positive regulation of ascospore formation; IMP:AspGD.
DR   GO; GO:0033246; P:positive regulation of penicillin metabolic process; IMP:AspGD.
DR   GO; GO:0010914; P:positive regulation of sterigmatocystin biosynthetic process; IMP:AspGD.
DR   GO; GO:1900376; P:regulation of secondary metabolite biosynthetic process; IMP:AspGD.
DR   GO; GO:0045460; P:sterigmatocystin metabolic process; IMP:AspGD.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   1: Evidence at protein level;
KW   Methylation; Methyltransferase; Nucleus; Reference proteome;
KW   S-adenosyl-L-methionine; Sporulation; Transcription;
KW   Transcription regulation; Transferase; Virulence.
FT   CHAIN           1..374
FT                   /note="Protein-methionine methyltransferase laeA"
FT                   /id="PRO_0000435741"
FT   REGION          1..75
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        19..45
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         207
FT                   /note="S-methylmethionine"
FT                   /evidence="ECO:0000269|PubMed:23532849"
FT   MUTAGEN         207
FT                   /note="M->A: Abolishes self-methylation."
FT                   /evidence="ECO:0000269|PubMed:23532849"
SQ   SEQUENCE   374 AA;  42965 MW;  89C49642CF984B32 CRC64;
     MFEMGPVGTR LPAMTSPAHN HYSYHSPTSS DRGRSRQNSD AMDIQSITER EPATRYAVAG
     GPAPWNRNGS PSMSPMYSNN SERNQFHEEN GRTYHGFRRG MYFLPCDEQE QDRLDIFHKL
     FTVARVSESL IYAPHPTNGR FLDLGCGTGI WAIEVANKYP DAFVAGVDLA PIQPPNHPKN
     CEFYAPFDFE APWAMGEDSW DLIHLQMGCG SVMGWPNLYR RIFAHLRPGA WFEQVEIDFE
     PRCDDRSLDG TALRHWYDCL KQATAETMRP IAHSSRDTIK DLQDAGFTEI DHQIVGLPLN
     PWHQDEHERK VARWYNLAVS ESIENLSLAP FSRVYRWPLE RIQQLAADVK SEAFNKEIHA
     YNILHIYQAR KPLR
 
 
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