MPKA_ASPFU
ID MPKA_ASPFU Reviewed; 424 AA.
AC Q4WQR3;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Mitogen-activated protein kinase mpkA {ECO:0000303|PubMed:19715768};
DE Short=MAP kinase mpkA {ECO:0000303|PubMed:19715768};
DE EC=2.7.11.24 {ECO:0000269|PubMed:33705521};
GN Name=mpkA {ECO:0000303|PubMed:19715768}; ORFNames=AFUA_4G13720;
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 [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 [2]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, PHOSPHORYLATION, AND ACTIVITY
RP REGULATION.
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 [3]
RP FUNCTION.
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 [4]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=25911225; DOI=10.1128/ec.00008-15;
RA Bom V.L., de Castro P.A., Winkelstroeter L.K., Marine M., Hori J.I.,
RA Ramalho L.N., dos Reis T.F., Goldman M.H., Brown N.A., Rajendran R.,
RA Ramage G., Walker L.A., Munro C.A., Rocha M.C., Malavazi I., Hagiwara D.,
RA Goldman G.H.;
RT "The Aspergillus fumigatus sitA phosphatase homologue is important for
RT adhesion, cell wall integrity, biofilm formation, and virulence.";
RL Eukaryot. Cell 14:728-744(2015).
RN [5]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=27473315; DOI=10.1534/g3.116.031112;
RA Rocha M.C., Fabri J.H., Franco de Godoy K., Alves de Castro P., Hori J.I.,
RA Ferreira da Cunha A., Arentshorst M., Ram A.F., van den Hondel C.A.,
RA Goldman G.H., Malavazi I.;
RT "Aspergillus fumigatus MADS-Box transcription factor rlmA is required for
RT regulation of the cell wall integrity and virulence.";
RL G3 (Bethesda) 6:2983-3002(2016).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION, AND INTERACTION WITH FLBB;
RP FLBC; BRLA AND RASB.
RX PubMed=32005734; DOI=10.1128/aem.02347-19;
RA Rocha M.C., Fabri J.H.T.M., Simoes I.T., Silva-Rocha R., Hagiwara D.,
RA da Cunha A.F., Goldman G.H., Canovas D., Malavazi I.;
RT "The cell wall integrity pathway contributes to the early stages of
RT Aspergillus fumigatus asexual development.";
RL Appl. Environ. Microbiol. 86:0-0(2020).
RN [7]
RP FUNCTION, AND INTERACTION WITH HSP90.
RX PubMed=33010083; DOI=10.1111/cmi.13273;
RA Rocha M.C., Minari K., Fabri J.H.T.M., Kerkaert J.D., Gava L.M.,
RA da Cunha A.F., Cramer R.A., Borges J.C., Malavazi I.;
RT "Aspergillus fumigatus Hsp90 interacts with the main components of the cell
RT wall integrity pathway and cooperates in heat shock and cell wall stress
RT adaptation.";
RL Cell. Microbiol. 23:e13273-e13273(2021).
RN [8]
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 protein kinase; part of cell wall integrity
CC (CWI) signaling pathway composed of pkcA, the bck1-mkk2-mpka MAPK
CC cascade and the downstream rlmA transcription regulator
CC (PubMed:19715768). The CWI signaling pathway regulates cell wall
CC integrity and pyomelanin formation (PubMed:19715768). CWI controls also
CC oxidative stress response, gliotoxin production, iron adaptation and
CC asexual development (PubMed:21883519, PubMed:32005734). Finally, CWI is
CC constitutively required for A.fumigatus to cope with the temperature
CC increase found in the mammalian lung environment, during infection
CC (PubMed:33010083). MpkA positively modulates the expression of
CC fumiquinazoline cluster during conidiogenesis and directly
CC phosphorylates fmqC, and perhaps also fmqA (PubMed:33705521).
CC {ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:21883519,
CC ECO:0000269|PubMed:32005734, ECO:0000269|PubMed:33010083,
CC 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:0000269|PubMed:33705521};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:33705521};
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:0000269|PubMed:33705521};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:33705521};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|RuleBase:RU361165};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation by the upstreamm MAPKK mkk2.
CC {ECO:0000269|PubMed:19715768}.
CC -!- SUBUNIT: Interacts with flbB, flbC, brlA, and rasB (PubMed:32005734).
CC Interacts with fmqA and fmqC (PubMed:33705521). Interacts with hsp90
CC (PubMed:33010083). {ECO:0000269|PubMed:32005734,
CC ECO:0000269|PubMed:33010083, ECO:0000269|PubMed:33705521}.
CC -!- INDUCTION: Expression is induced by cell wall-disturbing compounds.
CC {ECO:0000269|PubMed:19715768}.
CC -!- PTM: Phosphorylated by the upstreamm MAPKK mkk2 (PubMed:19715768).
CC Phosphorylation is induced during asexual development (PubMed:25911225,
CC PubMed:32005734). Phosphorylation is regulated by rlmA
CC (PubMed:27473315). {ECO:0000269|PubMed:19715768,
CC ECO:0000269|PubMed:25911225, ECO:0000269|PubMed:27473315,
CC ECO:0000269|PubMed:32005734}.
CC -!- DISRUPTION PHENOTYPE: Results in severe sensitivity against cell wall-
CC disturbing compounds congo red or calcofluor white, and drastic
CC alterations of the fungal morphology (PubMed:19715768). Leads to
CC reduced conidiation during asexual differentiation (PubMed:32005734).
CC Abolishes the production of fumiquinazoline C (PubMed:33705521).
CC {ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:32005734,
CC 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; AAHF01000005; EAL89421.1; -; Genomic_DNA.
DR RefSeq; XP_751459.1; XM_746366.1.
DR SMR; Q4WQR3; -.
DR STRING; 746128.CADAFUBP00006880; -.
DR EnsemblFungi; EAL89421; EAL89421; AFUA_4G13720.
DR GeneID; 3509230; -.
DR KEGG; afm:AFUA_4G13720; -.
DR VEuPathDB; FungiDB:Afu4g13720; -.
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q4WQR3; -.
DR OMA; MDIPRPE; -.
DR OrthoDB; 741207at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0000196; P:cell wall integrity MAPK cascade; IEA:EnsemblFungi.
DR GO; GO:0070370; P:cellular heat acclimation; IMP:AspGD.
DR GO; GO:0071469; P:cellular response to alkaline pH; IMP:AspGD.
DR GO; GO:0034605; P:cellular response to heat; IMP:AspGD.
DR GO; GO:0071852; P:fungal-type cell wall organization or biogenesis; IMP:AspGD.
DR GO; GO:0030448; P:hyphal growth; IMP:AspGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
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 GO; GO:0048021; P:regulation of melanin biosynthetic process; IMP:AspGD.
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; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..424
FT /note="Mitogen-activated protein kinase mpkA"
FT /id="PRO_0000453186"
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 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
