MKC1_CANAL
ID MKC1_CANAL Reviewed; 509 AA.
AC Q5AAG6; A0A1D8PRN9;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Mitogen-activated protein kinase MKC1 {ECO:0000305};
DE Short=MAP kinase MKC1 {ECO:0000305};
DE EC=2.7.11.24 {ECO:0000250|UniProtKB:Q00772};
GN Name=MKC1 {ECO:0000303|PubMed:7891715}; OrderedLocusNames=CAALFM_CR00120CA;
GN ORFNames=CaO19.7523;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP IDENTIFICATION, DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7891715; DOI=10.1128/mcb.15.4.2197;
RA Navarro-Garcia F., Sanchez M., Pla J., Nombela C.;
RT "Functional characterization of the MKC1 gene of Candida albicans, which
RT encodes a mitogen-activated protein kinase homolog related to cell
RT integrity.";
RL Mol. Cell. Biol. 15:2197-2206(1995).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9009353; DOI=10.1128/iai.65.2.833-837.1997;
RA Diez-Orejas R., Molero G., Navarro-Garcia F., Pla J., Nombela C.,
RA Sanchez-Perez M.;
RT "Reduced virulence of Candida albicans MKC1 mutants: a role for mitogen-
RT activated protein kinase in pathogenesis.";
RL Infect. Immun. 65:833-837(1997).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9493378; DOI=10.1099/00221287-144-2-411;
RA Navarro-Garcia F., Alonso-Monge R., Rico H., Pla J., Sentandreu R.,
RA Nombela C.;
RT "A role for the MAP kinase gene MKC1 in cell wall construction and
RT morphological transitions in Candida albicans.";
RL Microbiology 144:411-424(1998).
RN [7]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16304189; DOI=10.1128/aac.49.12.5146-5148.2005;
RA Wiederhold N.P., Kontoyiannis D.P., Prince R.A., Lewis R.E.;
RT "Attenuation of the activity of caspofungin at high concentrations against
RT candida albicans: possible role of cell wall integrity and calcineurin
RT pathways.";
RL Antimicrob. Agents Chemother. 49:5146-5148(2005).
RN [8]
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=15843378; DOI=10.1074/jbc.m502162200;
RA Bates S., MacCallum D.M., Bertram G., Munro C.A., Hughes H.B.,
RA Buurman E.T., Brown A.J., Odds F.C., Gow N.A.;
RT "Candida albicans Pmr1p, a secretory pathway P-type Ca2+/Mn2+-ATPase, is
RT required for glycosylation and virulence.";
RL J. Biol. Chem. 280:23408-23415(2005).
RN [9]
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=15817773; DOI=10.1099/mic.0.27723-0;
RA Arana D.M., Nombela C., Alonso-Monge R., Pla J.;
RT "The Pbs2 MAP kinase kinase is essential for the oxidative-stress response
RT in the fungal pathogen Candida albicans.";
RL Microbiology 151:1033-1049(2005).
RN [10]
RP PHOSPHORYLATION.
RX PubMed=16079350; DOI=10.1099/mic.0.28038-0;
RA Navarro-Garcia F., Eisman B., Fiuza S.M., Nombela C., Pla J.;
RT "The MAP kinase Mkc1p is activated under different stress conditions in
RT Candida albicans.";
RL Microbiology 151:2737-2749(2005).
RN [11]
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=15800048; DOI=10.1073/pnas.0407097102;
RA Kumamoto C.A.;
RT "A contact-activated kinase signals Candida albicans invasive growth and
RT biofilm development.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:5576-5581(2005).
RN [12]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16179009; DOI=10.1111/j.1365-3083.2005.01657.x;
RA Molero G., Guillen M.V., Martinez-Solano L., Gil C., Pla J., Nombela C.,
RA Sanchez-Perez M., Diez-Orejas R.;
RT "The importance of the phagocytes' innate response in resolution of the
RT infection induced by a low virulent Candida albicans mutant.";
RL Scand. J. Immunol. 62:224-233(2005).
RN [13]
RP FUNCTION.
RX PubMed=20865172; DOI=10.1371/journal.ppat.1001069;
RA LaFayette S.L., Collins C., Zaas A.K., Schell W.A., Betancourt-Quiroz M.,
RA Gunatilaka A.A., Perfect J.R., Cowen L.E.;
RT "PKC signaling regulates drug resistance of the fungal pathogen Candida
RT albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.";
RL PLoS Pathog. 6:E1001069-E1001069(2010).
RN [14]
RP FUNCTION.
RX PubMed=24475243; DOI=10.1371/journal.pone.0087128;
RA Prieto D., Roman E., Correia I., Pla J.;
RT "The HOG pathway is critical for the colonization of the mouse
RT gastrointestinal tract by Candida albicans.";
RL PLoS ONE 9:E87128-E87128(2014).
CC -!- FUNCTION: Serine/threonine protein kinase component of the cell
CC integrity pathway, a signal transduction pathway that plays a role in
CC yeast cell morphogenesis and cell growth. Participates in cell wall
CC construction, azole resistance, and host interaction. Required for the
CC signaling for invasive filamentous growth and biofilm formation, and
CC plays a crucial role in virulence. {ECO:0000269|PubMed:15800048,
CC ECO:0000269|PubMed:15817773, ECO:0000269|PubMed:15843378,
CC ECO:0000269|PubMed:16179009, ECO:0000269|PubMed:20865172,
CC ECO:0000269|PubMed:24475243, ECO:0000269|PubMed:9009353,
CC ECO:0000269|PubMed:9493378, ECO:0000303|PubMed:7891715}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q00772};
CC -!- INDUCTION: Expression is up-regulated by caspofungin.
CC {ECO:0000269|PubMed:16304189}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC {ECO:0000250|UniProtKB:Q00772}.
CC -!- PTM: Activated through phosphorylation of Thr-211 and Tyr-213 from the
CC TXY motif (By similarity). Phosphorylated in a PKC1-dependent manner in
CC response to cell wall perturbations, oxidative stress, osmotic stress,
CC and low temperatures. Also activated in response to physical contact
CC leading to contact-dependent cellular behaviors such as invasive hyphal
CC growth and biofilm development. Phosphorylation is also PBS2- and HOG1-
CC dependent. {ECO:0000250|UniProtKB:Q00772, ECO:0000269|PubMed:15800048,
CC ECO:0000269|PubMed:15817773, ECO:0000269|PubMed:15843378,
CC ECO:0000269|PubMed:16079350}.
CC -!- DISRUPTION PHENOTYPE: Leads to thermosensitive growth, enhanced
CC caffeine and caspofungin sensitivity, and alterations of cell surfaces.
CC Leads also to a decreased pathogenicity in mice through displaying a
CC greater susceptibility to nitric oxide (NO), a reduced inhibitory
CC effect on macrophage NO production, and an increased capacity of
CC macrophage stimulation by cell wall extracts.
CC {ECO:0000269|PubMed:16179009, ECO:0000269|PubMed:7891715,
CC ECO:0000269|PubMed:9009353, ECO:0000269|PubMed:9493378}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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DR EMBL; CP017630; AOW30783.1; -; Genomic_DNA.
DR RefSeq; XP_718680.1; XM_713587.1.
DR AlphaFoldDB; Q5AAG6; -.
DR SMR; Q5AAG6; -.
DR BioGRID; 1222804; 4.
DR STRING; 237561.Q5AAG6; -.
DR PRIDE; Q5AAG6; -.
DR GeneID; 3639710; -.
DR KEGG; cal:CAALFM_CR00120CA; -.
DR CGD; CAL0000183747; MKC1.
DR VEuPathDB; FungiDB:CR_00120C_A; -.
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q5AAG6; -.
DR OMA; MDIPRPE; -.
DR OrthoDB; 741207at2759; -.
DR Proteomes; UP000000559; Chromosome R.
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; IGI:CGD.
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:0034605; P:cellular response to heat; IMP:CGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:CGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0036170; P:filamentous growth of a population of unicellular organisms in response to starvation; IMP:CGD.
DR GO; GO:0031505; P:fungal-type cell wall organization; IMP:CGD.
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:1900436; P:positive regulation of filamentous growth of a population of unicellular organisms in response to starvation; IMP:CGD.
DR GO; GO:0006468; P:protein phosphorylation; IGI:CGD.
DR GO; GO:0060237; P:regulation of fungal-type cell wall organization; IMP:CGD.
DR GO; GO:1900231; P:regulation of single-species biofilm formation on inanimate substrate; IMP:CGD.
DR GO; GO:0007165; P:signal transduction; IGI:CGD.
DR GO; GO:0044011; P:single-species biofilm formation on inanimate substrate; IMP:CGD.
DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IEP:CGD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Coiled coil; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transferase; Virulence.
FT CHAIN 1..509
FT /note="Mitogen-activated protein kinase MKC1"
FT /id="PRO_0000430559"
FT DOMAIN 28..339
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 400..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 392..423
FT /evidence="ECO:0000255"
FT MOTIF 211..213
FT /note="TXY"
FT /evidence="ECO:0000250|UniProtKB:Q00772"
FT COMPBIAS 400..419
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 174
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 34..42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305"
FT MOD_RES 213
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 59036 MW; 4752084A053CA510 CRC64;
MDQQEAPIYY GRSVNKVYNQ EFIIDSRFKI VKELGHGAYG IVCSAKYDNG SKKVPDSNNG
NASSSANASF VAIKKITNIF SKNILCKRAL RELKLLQFFR GHKNITCLYD LDIIPNPMTG
EFNEIYLYEE LMECDMHQII RSGQPLSDQH YQSFIYQVLC GLNFIHSADV LHRDLKPGNL
LVNADCELKI CDFGLARGFS ENPDENAGFM TEYVATRWYR APEIMLSFTN YTKAIDIWSV
GCILAELLGG KPLFRGKDYV DQLNQILMIL GTPPESTLQR IGSHRAQNYV RSLPITRKAS
YEELFPDANP LALDLLERML TLDPRERITV RDALNHKYLE LWHDPKEEIE CQVKFDFKSF
ETVDGLDEMK QLIMDEVQKF REFVRKPIEE QQRIQMQLHM QKREEQRQEE EEKELLEQQR
QFPAQESMDI SQTPYNNLET NIGTPQVEDD YPRPQELDEF TFSNLESSSS MNLFQDMAKP
SGEEYIKLEE ELGFGLDGAM FNNYCNDHQ
