MKK2_ASPFU
ID MKK2_ASPFU Reviewed; 503 AA.
AC Q4WJJ0;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Mitogen-activated protein kinase kinae mkk2 {ECO:0000303|PubMed:19715768};
DE Short=MAPKK mkk2 {ECO:0000303|PubMed:19715768};
DE EC=2.7.11.24 {ECO:0000269|PubMed:19715768};
DE AltName: Full=MEK mkk2 {ECO:0000305};
GN Name=mkk2 {ECO:0000303|PubMed:19715768}; ORFNames=AFUA_1G05800;
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, AND DISRUPTION PHENOTYPE.
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.
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 [5]
RP FUNCTION.
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).
CC -!- FUNCTION: Mitogen-activated protein kinase kinase; part of the cell
CC wall integrity (CWI) signaling pathway composed of pkcA, the bck1-mkk2-
CC mpka MAPK 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). Mkk2 directly activates mpkA during vegetative
CC growth and under cell wall stress conditions (PubMed:19715768).
CC {ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:21883519,
CC ECO:0000269|PubMed:32005734, ECO:0000269|PubMed:33010083}.
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:19715768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:19715768};
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:19715768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:19715768};
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). Impairs
CC phosphorylation of mpkA (PubMed:19715768).
CC {ECO:0000269|PubMed:19715768}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000007; EAL88292.1; -; Genomic_DNA.
DR RefSeq; XP_750330.1; XM_745237.1.
DR SMR; Q4WJJ0; -.
DR STRING; 746128.CADAFUBP00000607; -.
DR EnsemblFungi; EAL88292; EAL88292; AFUA_1G05800.
DR GeneID; 3507589; -.
DR KEGG; afm:AFUA_1G05800; -.
DR VEuPathDB; FungiDB:Afu1g05800; -.
DR eggNOG; KOG0581; Eukaryota.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q4WJJ0; -.
DR OMA; DGTEMNP; -.
DR OrthoDB; 688282at2759; -.
DR Proteomes; UP000002530; Chromosome 1.
DR GO; GO:0005737; C:cytoplasm; IEA:EnsemblFungi.
DR GO; GO:0000935; C:division septum; IEA:EnsemblFungi.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; IEA:EnsemblFungi.
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: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:0030448; P:hyphal growth; IMP:AspGD.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:EnsemblFungi.
DR GO; GO:0006468; P:protein phosphorylation; IMP:AspGD.
DR GO; GO:0010810; P:regulation of cell-substrate adhesion; IMP:AspGD.
DR GO; GO:0048021; P:regulation of melanin biosynthetic process; IMP:AspGD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 3: Inferred from homology;
KW ATP-binding; Kinase; Nucleotide-binding; Reference proteome; Transferase;
KW Virulence.
FT CHAIN 1..503
FT /note="Mitogen-activated protein kinase kinae mkk2"
FT /id="PRO_0000453185"
FT DOMAIN 211..481
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..31
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 217..225
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 240
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 503 AA; 54781 MW; A763A873AA99F4BA CRC64;
MSSSPVPLLR PPVPGNRGNG PRPPKLTLGI PPSPNSRPVD GNGVGPAAAA PEAPQPQRPS
TRPAPPQLRL ATPMGSSSDV PQEVPRLANG RPAPPPLATT GLNESTGHSR SSSFTYLDGK
ASGPASASSS NYSALSFAMG LRQPHGSTPD PSSAISSVYS DREGGVQMER DNSVNGLLPD
LDKLSLEKGR PLDVDDLDDE GWLAASEQKK IIELGSLGEG AGGAVTRCKL KDGKTVFALK
IITTDPNPDV KKQIVRELNF NKDCASEHIC RYYGAFMDKS TGTISIAMEF CEGGSLDSIY
KEVKKLGGRT GEKVLGKIAE GVLNGLTYLH SRKIIHRDIK PSNILLCRNG QVKLCDFGVS
GEFGTKGDAN TFIGTSYYMA PERITGQSYT ITSDVWSLGV TLLEVAQHRF PFPADGTEMQ
PRAGLIDLLT YIVRQPIPKL KDEPENRIRW SDNFKYFIEC CLEKEPPRRA TPWRMLEHPW
MLDMKNKKVN MANFVRQVWG WQD
