MPKA_ASPFC
ID MPKA_ASPFC Reviewed; 424 AA.
AC B0Y4X4;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Mitogen-activated protein kinase mpkA {ECO:0000303|PubMed:17981060};
DE Short=MAPK mpkA {ECO:0000303|PubMed:17981060};
DE EC=2.7.11.24 {ECO:0000305|PubMed:17981060};
GN Name=mpkA {ECO:0000303|PubMed:17981060}; ORFNames=AFUB_070630;
OS Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) (Aspergillus
OS fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=451804;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CEA10 / CBS 144.89 / FGSC A1163;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION, AND INDUCTION.
RX PubMed=17981060; DOI=10.1016/j.fgb.2007.09.006;
RA Valiante V., Heinekamp T., Jain R., Haertl A., Brakhage A.A.;
RT "The mitogen-activated protein kinase MpkA of Aspergillus fumigatus
RT regulates cell wall signaling and oxidative stress response.";
RL Fungal Genet. Biol. 45:618-627(2008).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=19715768; DOI=10.1016/j.fgb.2009.08.005;
RA Valiante V., Jain R., Heinekamp T., Brakhage A.A.;
RT "The MpkA MAP kinase module regulates cell wall integrity signaling and
RT pyomelanin formation in Aspergillus fumigatus.";
RL Fungal Genet. Biol. 46:909-918(2009).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=21883519; DOI=10.1111/j.1365-2958.2011.07778.x;
RA Jain R., Valiante V., Remme N., Docimo T., Heinekamp T., Hertweck C.,
RA Gershenzon J., Haas H., Brakhage A.A.;
RT "The MAP kinase MpkA controls cell wall integrity, oxidative stress
RT response, gliotoxin production and iron adaptation in Aspergillus
RT fumigatus.";
RL Mol. Microbiol. 82:39-53(2011).
RN [5]
RP PHOSPHORYLATION.
RX PubMed=26878695; DOI=10.1111/mmi.13354;
RA Bruder Nascimento A.C., Dos Reis T.F., de Castro P.A., Hori J.I., Bom V.L.,
RA de Assis L.J., Ramalho L.N., Rocha M.C., Malavazi I., Brown N.A.,
RA Valiante V., Brakhage A.A., Hagiwara D., Goldman G.H.;
RT "Mitogen activated protein kinases SakA(HOG1) and MpkC collaborate for
RT Aspergillus fumigatus virulence.";
RL Mol. Microbiol. 100:841-859(2016).
RN [6]
RP FUNCTION.
RX PubMed=30914505; DOI=10.1128/mbio.00215-19;
RA Manfiolli A.O., Siqueira F.S., Dos Reis T.F., Van Dijck P., Schrevens S.,
RA Hoefgen S., Foege M., Strassburger M., de Assis L.J., Heinekamp T.,
RA Rocha M.C., Janevska S., Brakhage A.A., Malavazi I., Goldman G.H.,
RA Valiante V.;
RT "Mitogen-activated protein kinase cross-talk interaction modulates the
RT production of melanins in Aspergillus fumigatus.";
RL MBio 10:0-0(2019).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH FMQA AND FMQC.
RX PubMed=33705521; DOI=10.1093/genetics/iyab036;
RA Rocha M.C., Fabri J.H.T.M., da Silva L.P., Angolini C.F.F., Bertolini M.C.,
RA da Cunha A.F., Valiante V., Goldman G.H., Fill T.P., Malavazi I.;
RT "Transcriptional control of the production of Aspergillus fumigatus
RT conidia-borne secondary metabolite fumiquinazoline C important for
RT phagocytosis protection.";
RL Genetics 0:0-0(2021).
CC -!- FUNCTION: Mitogen-activated kinase (MAPK), part of the cell wall
CC integrity (CWI) signaling pathway composed by three protein kinases
CC bck1, mkk2 and mpkA and responsible for the maintaining of cell-wall
CC integrity balance (PubMed:17981060, PubMed:19715768). The CWI pathway
CC regulates also the oxidative stress response, as well as the production
CC of some secondary metabolites including gliotoxin, pyomelanin,
CC pseurotin A, fumiquinazoline C or dihydroxynaphthalene (DHN)-melanin
CC (PubMed:19715768, PubMed:21883519, PubMed:30914505, PubMed:33705521).
CC MpkA directly phosphorylates the fumiquinazoline C biosynthesis cluster
CC nonribosomal peptide synthetase fmqC during conidiation
CC (PubMed:33705521). Mpka is also required for adaptation to iron
CC starvation and regulates the expression of genes involved in
CC siderophore biosynthesis in a hapX/sreA-independent manner
CC (PubMed:21883519). {ECO:0000269|PubMed:17981060,
CC ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:21883519,
CC ECO:0000269|PubMed:30914505, ECO:0000269|PubMed:33705521}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24;
CC Evidence={ECO:0000305|PubMed:17981060};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000305|PubMed:17981060};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.24; Evidence={ECO:0000305|PubMed:17981060};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000255|RuleBase:RU361165};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:17981060};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation. {ECO:0000255|RuleBase:RU361165}.
CC -!- SUBUNIT: Interacts with the fumiquinazoline C biosynthesis cluster
CC nonribosomal peptide synthetases fmqA and fmqC.
CC {ECO:0000269|PubMed:33705521}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21883519}.
CC Note=Accumulates in the nucleus under iron depletion conditions.
CC {ECO:0000269|PubMed:21883519}.
CC -!- INDUCTION: Expression is induced by cell wall integrity inhibitors such
CC as glucanex, SDS, congo red and caffeine.
CC {ECO:0000269|PubMed:17981060}.
CC -!- PTM: Phosphorylated during cell wall stress by the upstream MAPKK mkk2
CC (PubMed:17981060). Iron starvation triggers phosphorylation and thus
CC activation of mpkA (PubMed:21883519). Phosphorylation increases upon
CC osmotic stress and cell wall damage and depends on mpkC and sakA
CC (PubMed:26878695). {ECO:0000269|PubMed:17981060,
CC ECO:0000269|PubMed:21883519, ECO:0000269|PubMed:26878695}.
CC -!- DISRUPTION PHENOTYPE: Leads to the formation of thicker hyphae, which
CC appear less elongated and form more branched hyphae (PubMed:17981060,
CC PubMed:19715768). Increases sensitivity to diamide and menadione but
CC shows increased tolerance against H(2)O(2) (PubMed:17981060). Results
CC also in increased sensitivity to cell wall integrity inhibitors such as
CC glucanex, SDS, congo red and calcofluor white (PubMed:19715768).
CC Affects the expression of genes involved in cell wall remodeling,
CC protection against ROS, secondary metabolism such as gliotoxin,
CC pyomelanin and pseurotin A, as well as genes involved in siderophore
CC biosynthesis (PubMed:21883519). Affects also the expression of
CC fumiquinazoline C biosynthesis cluster genes (PubMed:33705521). Does
CC not affect the formation of conidiophores and conidia, nor the
CC germination of aconidia (PubMed:17981060). Does not affect the
CC virulence in a low dose murine infection model (PubMed:17981060).
CC {ECO:0000269|PubMed:17981060, ECO:0000269|PubMed:19715768,
CC ECO:0000269|PubMed:21883519, ECO:0000269|PubMed:33705521}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; DS499598; EDP50723.1; -; Genomic_DNA.
DR SMR; B0Y4X4; -.
DR EnsemblFungi; EDP50723; EDP50723; AFUB_070630.
DR VEuPathDB; FungiDB:AFUB_070630; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR PhylomeDB; B0Y4X4; -.
DR Proteomes; UP000001699; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:EnsemblFungi.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0000196; P:cell wall integrity MAPK cascade; IEA:EnsemblFungi.
DR GO; GO:1902660; P:negative regulation of glucose mediated signaling pathway; IEA:EnsemblFungi.
DR GO; GO:1902413; P:negative regulation of mitotic cytokinesis; IEA:EnsemblFungi.
DR GO; GO:1905665; P:positive regulation of calcium ion import across plasma membrane; IEA:EnsemblFungi.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:EnsemblFungi.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Magnesium; Nucleotide-binding; Nucleus;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..424
FT /note="Mitogen-activated protein kinase mpkA"
FT /id="PRO_0000454881"
FT DOMAIN 23..314
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 375..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 29..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 424 AA; 48466 MW; 06E39C8E15D5A6CB CRC64;
MSDLQGRKVF KVFNQDFIVD ERYNVTKELG QGAYGIVCAA TNVHTGEGVA IKKVTNVFSK
KILAKRALRE IKLLQHFRGH RNITCLYDMD IPRPDNFNET YLYEELMECD LAAIIRSGQP
LTDAHFQSFI YQILCGLKYI HSANVLHRDL KPGNLLVNAD CELKICDFGL ARGFSIDPEE
NAGYMTEYVA TRWYRAPEIM LSFQSYTKAI DVWSVGCILA ELLGGRPFFK GRDYVDQLNQ
ILHYLGTPNE ETLSRIGSPR AQEYVRNLPF MPKIPFQRLF PNANPDALDL LDRMLAFDPA
SRISVEEALE HPYLHIWHDA SDEPTCPTTF DFHFEVVDDV QEMRKMIYDE VVRFRNLVRQ
QSQAQAAAAA QQQQQQIAQQ TNVPIPDHQQ GGWKQEEPKP QEVHAAGGHV NDLESSLQRG
MDVQ
