PDK1_CRYNH
ID PDK1_CRYNH Reviewed; 1230 AA.
AC J9VH94;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=Serine/threonine-protein kinase PDK1 {ECO:0000303|PubMed:22339665};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q12701};
GN Name=PDK1 {ECO:0000303|PubMed:22339665};
GN Synonyms=PKH2-02 {ECO:0000303|PubMed:23087368};
GN ORFNames=CNAG_02915 {ECO:0000312|EMBL:AFR93777.2};
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443 {ECO:0000312|Proteomes:UP000010091};
RN [1] {ECO:0000312|Proteomes:UP000010091}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22339665; DOI=10.1111/j.1365-2958.2012.08016.x;
RA Lee H., Khanal Lamichhane A., Garraffo H.M., Kwon-Chung K.J., Chang Y.C.;
RT "Involvement of PDK1, PKC and TOR signalling pathways in basal fluconazole
RT tolerance in Cryptococcus neoformans.";
RL Mol. Microbiol. 84:130-146(2012).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=CM018;
RX PubMed=23087368; DOI=10.1128/ec.00235-12;
RA Chabrier-Rosello Y., Gerik K.J., Koselny K., DiDone L., Lodge J.K.,
RA Krysan D.J.;
RT "Cryptococcus neoformans phosphoinositide-dependent kinase 1 (PDK1)
RT ortholog is required for stress tolerance and survival in murine
RT phagocytes.";
RL Eukaryot. Cell 12:12-22(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase that functions in the
CC sphingolipid-mediated signaling pathway, regulating organization of the
CC plasma membrane (By similarity). May phosphorylate PKC1 to activate the
CC cell integrity MAPK cascade during cell wall and membrane stress
CC (PubMed:22339665, PubMed:23087368). May regulate sphingolipid
CC metabolism upstream of YPK1 (PubMed:22339665).
CC {ECO:0000250|UniProtKB:Q12236, ECO:0000269|PubMed:22339665,
CC ECO:0000269|PubMed:23087368}.
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 Evidence={ECO:0000250|UniProtKB:Q12701};
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; Evidence={ECO:0000250|UniProtKB:Q12701};
CC -!- DOMAIN: The protein kinase domain contains a 228 residue insertion
CC between the ATP binding site and the active site. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Cell integrity defects (PubMed:23087368).
CC Decreases virulence in a moth infection model (PubMed:23087368).
CC Decreases virulence in a mouse systemic infection model
CC (PubMed:22339665). Decreases cell population growth in macrophages
CC (PubMed:23087368). Abnormal sphingolipid metabolism (PubMed:22339665).
CC Sensitive to: high temperature; osmotic stress; sodium dodecyl sulfate;
CC Congo Red; caffeine; sirolimus; Calcofluor White; amphotericin B;
CC fluconazole; OSU-03012; hydrogen peroxide; diamide; sodium nitrite;
CC myriocin (phytosphingosine biosynthesis inhibitor); aureobasidin A
CC (inositol-containing sphingolipid biosynthesis inhibitor);
CC phytosphingosine; OSU-03012 and fluconazole (PubMed:22339665,
CC PubMed:23087368). Decreases PKC1 activation (PubMed:23087368).
CC Decreases MPK1 phosphorylation during cell wall stress induced by
CC Calcofluor White and fluconazole (PubMed:22339665, PubMed:23087368).
CC Decreases melanin levels (PubMed:23087368).
CC {ECO:0000269|PubMed:22339665, ECO:0000269|PubMed:23087368}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PDPK1 subfamily. {ECO:0000305}.
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DR EMBL; CP003822; AFR93777.2; -; Genomic_DNA.
DR RefSeq; XP_012047847.1; XM_012192457.1.
DR AlphaFoldDB; J9VH94; -.
DR SMR; J9VH94; -.
DR EnsemblFungi; AFR93777; AFR93777; CNAG_02915.
DR GeneID; 23886463; -.
DR VEuPathDB; FungiDB:CNAG_02915; -.
DR HOGENOM; CLU_290852_0_0_1; -.
DR PHI-base; PHI:2955; -.
DR Proteomes; UP000010091; Chromosome 3.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:1903139; P:positive regulation of cell wall integrity MAPK cascade; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0090153; P:regulation of sphingolipid biosynthetic process; IMP:UniProtKB.
DR CDD; cd05581; STKc_PDK1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR039046; PDPK1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
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; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..1230
FT /note="Serine/threonine-protein kinase PDK1"
FT /id="PRO_0000451207"
FT DOMAIN 281..801
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..522
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 907..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 972..1035
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..76
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..180
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..200
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..263
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 355..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 464..494
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..522
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 925..944
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 978..1000
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 666
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 291..293
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 319
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 621..623
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 670
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 684
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
SQ SEQUENCE 1230 AA; 130171 MW; B974A32158FF6A6C CRC64;
MASSHFGPAS PASSTPPPSS AYARLIAPTI TRNSSSSSSR STTTCSSTSS VQAVPMRPPP
IETSTAATSR SQLPSNRHSE NEAEHDTSYT SPGLSVGGRG GLARNGPRSN RLGTSPQARH
VPPSIVALSP SPSPILNMAS KRQSNTETVS GTSPSTPLGK SFLAQQDLSP NSSTIPLRVT
ISVDPNDRLS HDRESHSAER PRSSGNSPVR GRHGHLSTPS SPTNSYRALG GKPRTLSVDA
GQNWGGSHRS RARDGDDRER RQSQVSSASS GALKKHSLDD WVLGEELGVG SYSTVYCVTP
SANTHSPTSP QPARKYALKV INQAHLIQEK KVKYAMVERD ALIRLSDPRP SKGHKRGVSS
SSSSGYAQTG SAGKRRSTAS IGGQSSMASV SGGTVSNSKK DTRDRLSIVT TSSAASSPVL
TASSGSTQLS PTAVSGGGGN IKGRRPSRSA EPPTPVQEQT EMLIRGGEDG KDGQDGQETP
SREWDRDRDW DNMTRSRPPS PVREESAEGG EKEKDEEERS GAEPVELGAA IHLTLPPPQI
PSTPEPRGSP LLSTDGHRTS RETPRDRPHL TPKRRRQSLA PSERSVKSAS TTGKMSAAAH
PGVVRLYSTF NDSSSLYFVL SLASNGELAS IIRKHGSLDI TSARYYAAQL IDTLEFVHSR
GVIHRDLKPE NILLDEDMRI KITDFGSAKI IAKDEPIVDD SSRSRSFVGS ADFVSPEVLR
NEVATTASDI WAFGCVLYQF ICGKPPFRGA TDYLTFQKIL KREVEFPKGI DEDAKSLIDT
ILDLEPNLRP SITFIKTHPF FQSIDFSTLW TIPAPPISSG LREPSKSTTL AQLEASDIWG
VFEGSDVGEE DEDGFEYDAD TVSPRPEGGA VGEGMMEPLF DRRAAASAVH NVDHPKFSRL
RNQYINLGED LDPPRPAYAG AGTGGRGKRE KEVEKKKGEK ARGLSHGSES SGGNRSALAG
WLEAIKFGGA GGGGMSGSAT SVAASDTVRT PGTGTGTGPG SRPGSRAGIP SFGLGPGSGS
RSNRGSGASM RSDEARDLSM SLGGLRMNMS KASEFDKWTP LLLANESIIF TSPITLRTSS
PALQLHLPAF LLPAPKKRQL VLTDFPRLLM IKDDNEADGD PAGSDSGAGL SSSSHVESGG
GGVGGGGRGG GHGSLRIKGE AVFVPRPSTA TGSSTTKGGG YSAVPNAVMD VQEKGSKGFT
VQTPGMVYYC HVDSVELRAK WMAAIHRVGL
