ID CLA4_CANAL Reviewed; 976 AA.
AC Q5APR8; A0A1D8PET2; Q5AP73;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 27-MAR-2024, entry version 143.
DE RecName: Full=Serine/threonine-protein kinase CLA4;
DE EC=2.7.11.1;
GN Name=CLA4; OrderedLocusNames=CAALFM_C110210CA;
GN ORFNames=CaO19.12355, CaO19.4890;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9259554; DOI=10.1016/s0960-9822(06)00252-1;
RA Leberer E., Ziegelbauer K., Schmidt A., Harcus D., Dignard D., Ash J.,
RA Johnson L., Thomas D.Y.;
RT "Virulence and hyphal formation of Candida albicans require the Ste20p-like
RT protein kinase CaCla4p.";
RL Curr. Biol. 7:539-546(1997).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10816502; DOI=10.1128/iai.68.6.3485-3490.2000;
RA Phan Q.T., Belanger P.H., Filler S.G.;
RT "Role of hyphal formation in interactions of Candida albicans with
RT endothelial cells.";
RL Infect. Immun. 68:3485-3490(2000).
RN [6]
RP FUNCTION.
RX PubMed=12455975; DOI=10.1128/ec.1.1.95-104.2002;
RA Ushinsky S.C., Harcus D., Ash J., Dignard D., Marcil A., Morchhauser J.,
RA Thomas D.Y., Whiteway M., Leberer E.;
RT "CDC42 is required for polarized growth in human pathogen Candida
RT albicans.";
RL Eukaryot. Cell 1:95-104(2002).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=12381467; DOI=10.1111/j.1574-695x.2002.tb00617.x;
RA Brennan M., Thomas D.Y., Whiteway M., Kavanagh K.;
RT "Correlation between virulence of Candida albicans mutants in mice and
RT Galleria mellonella larvae.";
RL FEMS Immunol. Med. Microbiol. 34:153-157(2002).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=12379711; DOI=10.1128/iai.70.11.6319-6329.2002;
RA Marcil A., Harcus D., Thomas D.Y., Whiteway M.;
RT "Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of
RT Candida genotype, infection ratios, and gamma interferon treatment.";
RL Infect. Immun. 70:6319-6329(2002).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=16002645; DOI=10.1128/ec.4.7.1191-1202.2005;
RA Martin S.W., Douglas L.M., Konopka J.B.;
RT "Cell cycle dynamics and quorum sensing in Candida albicans chlamydospores
RT are distinct from budding and hyphal growth.";
RL Eukaryot. Cell 4:1191-1202(2005).
RN [10]
RP FUNCTION, DOMAIN, AND INTERACTION WITH CDC42.
RX PubMed=18022566; DOI=10.1016/j.chembiol.2007.10.008;
RA Su Z., Li H., Li Y., Ni F.;
RT "Inhibition of the pathogenically related morphologic transition in Candida
RT albicans by disrupting Cdc42 binding to its effectors.";
RL Chem. Biol. 14:1273-1282(2007).
CC -!- FUNCTION: Ser/Thr kinase required for wild-type filamentous growth,
CC chlamydospore formation, and virulence in mouse systemic infection.
CC {ECO:0000269|PubMed:10816502, ECO:0000269|PubMed:12455975,
CC ECO:0000269|PubMed:18022566, ECO:0000269|PubMed:9259554}.
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=2.7.11.1;
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=2.7.11.1;
CC -!- SUBUNIT: Interacts (via the CRIB domain) with CDC42.
CC {ECO:0000269|PubMed:18022566}.
CC -!- DOMAIN: The CRIB domain is involved in the interaction with CDC42.
CC {ECO:0000269|PubMed:18022566}.
CC -!- DISRUPTION PHENOTYPE: Leads to defects in morphology and hyphal
CC formation, impaired chlamydospore formation, reduced colonization of
CC the kidneys in infected mice and suppressed virulence in the mouse
CC model. {ECO:0000269|PubMed:10816502, ECO:0000269|PubMed:12379711,
CC ECO:0000269|PubMed:12381467, ECO:0000269|PubMed:16002645,
CC ECO:0000269|PubMed:9259554}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; CP017623; AOW26651.1; -; Genomic_DNA.
DR RefSeq; XP_723573.1; XM_718480.1.
DR AlphaFoldDB; Q5APR8; -.
DR SMR; Q5APR8; -.
DR BioGRID; 1217972; 1.
DR STRING; 237561.Q5APR8; -.
DR EnsemblFungi; C1_10210C_A-T; C1_10210C_A-T-p1; C1_10210C_A.
DR GeneID; 3634878; -.
DR KEGG; cal:CAALFM_C110210CA; -.
DR CGD; CAL0000192143; CLA4.
DR VEuPathDB; FungiDB:C1_10210C_A; -.
DR eggNOG; KOG0578; Eukaryota.
DR HOGENOM; CLU_000288_26_2_1; -.
DR InParanoid; Q5APR8; -.
DR OrthoDB; 460351at2759; -.
DR PHI-base; PHI:6803; -.
DR PRO; PR:Q5APR8; -.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IGI:CGD.
DR GO; GO:0009267; P:cellular response to starvation; IMP:CGD.
DR GO; GO:0001410; P:chlamydospore formation; IMP:CGD.
DR GO; GO:0044114; P:development of symbiont in host; IMP:CGD.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0036180; P:filamentous growth of a population of unicellular organisms in response to biotic stimulus; IMP:CGD.
DR GO; GO:0036170; P:filamentous growth of a population of unicellular organisms in response to starvation; IMP:CGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:1900445; P:positive regulation of filamentous growth of a population of unicellular organisms in response to biotic stimulus; IMP:CGD.
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:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR CDD; cd13279; PH_Cla4_Ste20; 1.
DR CDD; cd06614; STKc_PAK; 1.
DR Gene3D; 3.90.810.10; CRIB domain; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR48015; SERINE/THREONINE-PROTEIN KINASE TAO; 1.
DR PANTHER; PTHR48015:SF6; SERINE_THREONINE-PROTEIN KINASE CLA4-RELATED; 1.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 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; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Virulence.
FT CHAIN 1..976
FT /note="Serine/threonine-protein kinase CLA4"
FT /id="PRO_0000424377"
FT DOMAIN 73..184
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 237..250
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 685..940
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..522
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 559..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 367..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..498
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 559..600
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 608..645
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 808
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 691..699
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 715
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 976 AA; 107214 MW; D8AB228150E43C41 CRC64;
MTSIYTSDLK NHRRAPPPPN GAAGSGSGSS SGSGSGSGSG SGSGSLTNIV TSSNSLGVTA
NQTKPIQLNI NSSKRQSGWV HVKDDGIFTS FRWNKRFMVI NDKTLNFYKQ EPYSSDGNSN
SNTPDLSFPL YLINNINLKP NSGYSKTSQS FEIVPKNNNK SILISVKTNN DYLDWLDAFT
TKCPLVQIGE NNSGVSSSHP HLQIQHLTNG SLNGNSSSSP TSGLSSSSVL TGGNSGVSGP
INFTHKVHVG FDPASGNFTG LPDTWKSLLQ HSKITNEDWK KDPVAVIKVL EFYSDINGGN
SAAGTPIGSP MINSKTNNNN NDPNNYSSAK NNVQEANLQE WVKPPAKSTV SQFKPSRAAP
KPPTPYHLTQ LNGSSHQHTS SSGSLPSSGN NNNNNNSTNN NNTKNVSPLN NLMNKSELIP
ARRAPPPPTS GTSSDTYSNK NHQDRSGYEQ QRQQRTDSSQ QQQQQQKQHQ YQQKSQQQQQ
QPLSSHQGGT SHIPKQVPPT LPSSGPPTQA ASGKSMPSKI HPDLKIQQGT NNYIKSSGTD
ANQVDGDAKQ FIKPFNLQSK KSQQQLASKQ PSPPSSQQQQ QKPMTSHGLM GTSHSVTKPL
NPVNDPIKPL NLKSSKSKEA LNETSGVSKT PSPTDKSNKP TAPASGPAVT KTAKQLKKER
ERLNDLQIIA KLKTVVNNQD PKPLFRIVEK AGQGASGNVY LAEMIKDNNR KIAIKQMDLD
AQPRKELIIN EILVMKDSQH KNIVNFLDSY LIGDNELWVI MEYMQGGSLT EIIENNDFKL
NEKQIATICF ETLKGLQHLH KKHIIHRDIK SDNVLLDAYG NVKITDFGFC AKLTDQRNKR
ATMVGTPYWM APEVVKQKEY DEKVDVWSLG IMTIEMIEGE PPYLNEEPLK ALYLIATNGT
PKLKKPELLS NSIKKFLSIC LCVDVRYRAS TDELLEHSFI QHKSGKIEEL APLLEWKKQQ
QKHQQHKQET SDTGFA
//
