PKH2_YEAST
ID PKH2_YEAST Reviewed; 1081 AA.
AC Q12236; D6W1W8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Serine/threonine-protein kinase PKH2;
DE EC=2.7.11.1;
DE AltName: Full=PKB-activating kinase homolog 2;
GN Name=PKH2; OrderedLocusNames=YOL100W; ORFNames=HRC1081;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7502582; DOI=10.1002/yea.320111108;
RA Vandenbol M., Durand P., Portetelle D., Hilger F.;
RT "Sequence analysis of a 44 kb DNA fragment of yeast chromosome XV including
RT the Ty1-H3 retrotransposon, the suf1(+) frameshift suppressor gene for
RT tRNA-Gly, the yeast transfer RNA-Thr-1a and a delta element.";
RL Yeast 11:1069-1075(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=10074427; DOI=10.1016/s0960-9822(99)80088-8;
RA Casamayor A., Torrance P.D., Kobayashi T., Thorner J., Alessi D.R.;
RT "Functional counterparts of mammalian protein kinases PDK1 and SGK in
RT budding yeast.";
RL Curr. Biol. 9:186-197(1999).
RN [5]
RP FUNCTION.
RX PubMed=10567559; DOI=10.1128/mcb.19.12.8344;
RA Inagaki M., Schmelzle T., Yamaguchi K., Irie K., Hall M.N., Matsumoto K.;
RT "PDK1 homologs activate the Pkc1-mitogen-activated protein kinase pathway
RT in yeast.";
RL Mol. Cell. Biol. 19:8344-8352(1999).
RN [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11726514; DOI=10.1093/emboj/20.23.6783;
RA Friant S., Lombardi R., Schmelzle T., Hall M.N., Riezman H.;
RT "Sphingoid base signaling via Pkh kinases is required for endocytosis in
RT yeast.";
RL EMBO J. 20:6783-6792(2001).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12221112; DOI=10.1091/mbc.e02-04-0201;
RA Roelants F.M., Torrance P.D., Bezman N., Thorner J.;
RT "Pkh1 and Pkh2 differentially phosphorylate and activate Ypk1 and Ykr2 and
RT define protein kinase modules required for maintenance of cell wall
RT integrity.";
RL Mol. Biol. Cell 13:3005-3028(2002).
RN [8]
RP FUNCTION.
RX PubMed=15470109; DOI=10.1099/mic.0.27286-0;
RA Roelants F.M., Torrance P.D., Thorner J.;
RT "Differential roles of PDK1- and PDK2-phosphorylation sites in the yeast
RT AGC kinases Ypk1, Pkc1 and Sch9.";
RL Microbiology 150:3289-3304(2004).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18034155; DOI=10.1038/sj.emboj.7601933;
RA Walther T.C., Aguilar P.S., Frohlich F., Chu F., Moreira K.,
RA Burlingame A.L., Walter P.;
RT "Pkh-kinases control eisosome assembly and organization.";
RL EMBO J. 26:4946-4955(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1009, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138; SER-619 AND SER-1009,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [14]
RP FUNCTION.
RX PubMed=21163942; DOI=10.1074/jbc.m110.196030;
RA Luo G., Costanzo M., Boone C., Dickson R.C.;
RT "Nutrients and the Pkh1/2 and Pkc1 protein kinases control mRNA decay and
RT P-body assembly in Yeast.";
RL J. Biol. Chem. 286:8759-8770(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP DISRUPTION PHENOTYPE.
RX PubMed=23911092; DOI=10.1021/cb400452z;
RA Pastor-Flores D., Schulze J.O., Bahi A., Giacometti R., Ferrer-Dalmau J.,
RA Passeron S., Engel M., Suss E., Casamayor A., Biondi R.M.;
RT "PIF-pocket as a target for C. albicans Pkh selective inhibitors.";
RL ACS Chem. Biol. 8:2283-2292(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase which is part sphingolipid-
CC mediated signaling pathway that is required for the internalization
CC step of endocytosis by regulating eisosome assembly and organization,
CC and modulating the organization of the plasma membrane. Phosphorylates
CC and activates PKC1. Activates YPK1 and YPK2, 2 components of signaling
CC cascade required for maintenance of cell wall integrity. Required for
CC stress-induced P-body assembly and regulates global mRNA decay at the
CC deadenylation step. {ECO:0000269|PubMed:10074427,
CC ECO:0000269|PubMed:10567559, ECO:0000269|PubMed:11726514,
CC ECO:0000269|PubMed:12221112, ECO:0000269|PubMed:15470109,
CC ECO:0000269|PubMed:18034155, ECO:0000269|PubMed:21163942}.
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 -!- ACTIVITY REGULATION: Sphingoid base activates kinase activity.
CC {ECO:0000269|PubMed:11726514}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cell cortex. Note=Localizes
CC at eisosomes, large, immobile complexes that mark sites of endocytosis
CC near the plasma membrane.
CC -!- DOMAIN: The PIF-pocket is a small lobe in the catalytic domain required
CC by the enzyme for the binding to the hydrophobic motif of its
CC substrates. It is an allosteric regulatory site that can accommodate
CC small compounds acting as allosteric inhibitors.
CC {ECO:0000250|UniProtKB:O15530}.
CC -!- DISRUPTION PHENOTYPE: Long-term depletion of PKH2 in a PKH1 null mutant
CC (Pkh depletion) induces programmed cell death. This is mediated by the
CC lack of Pkh-dependent activation of the PKC1 downstream signaling
CC cascade and results in accumulation of reactive oxigen species (ROS)
CC and DNA fragmentation. {ECO:0000269|PubMed:23911092}.
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; Z48149; CAA88162.1; -; Genomic_DNA.
DR EMBL; Z74842; CAA99113.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10684.1; -; Genomic_DNA.
DR PIR; S51899; S51899.
DR RefSeq; NP_014541.1; NM_001183354.1.
DR AlphaFoldDB; Q12236; -.
DR SMR; Q12236; -.
DR BioGRID; 34303; 91.
DR DIP; DIP-6295N; -.
DR IntAct; Q12236; 18.
DR MINT; Q12236; -.
DR STRING; 4932.YOL100W; -.
DR iPTMnet; Q12236; -.
DR MaxQB; Q12236; -.
DR PaxDb; Q12236; -.
DR PRIDE; Q12236; -.
DR EnsemblFungi; YOL100W_mRNA; YOL100W; YOL100W.
DR GeneID; 854053; -.
DR KEGG; sce:YOL100W; -.
DR SGD; S000005460; PKH2.
DR VEuPathDB; FungiDB:YOL100W; -.
DR eggNOG; KOG0592; Eukaryota.
DR GeneTree; ENSGT00940000155267; -.
DR HOGENOM; CLU_005768_1_1_1; -.
DR InParanoid; Q12236; -.
DR OMA; QKVMKVQ; -.
DR BioCyc; YEAST:G3O-33498-MON; -.
DR Reactome; R-SCE-114604; GPVI-mediated activation cascade.
DR Reactome; R-SCE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-SCE-165158; Activation of AKT2.
DR Reactome; R-SCE-202424; Downstream TCR signaling.
DR Reactome; R-SCE-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-SCE-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-SCE-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-SCE-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-SCE-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-SCE-5625740; RHO GTPases activate PKNs.
DR Reactome; R-SCE-6804757; Regulation of TP53 Degradation.
DR Reactome; R-SCE-9634635; Estrogen-stimulated signaling through PRKCZ.
DR PRO; PR:Q12236; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q12236; protein.
DR GO; GO:0005938; C:cell cortex; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:SGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:SGD.
DR GO; GO:0000196; P:cell wall integrity MAPK cascade; IMP:SGD.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0032511; P:late endosome to vacuole transport via multivesicular body sorting pathway; IMP:SGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IGI:SGD.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IGI:SGD.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IMP:SGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:SGD.
DR GO; GO:0060211; P:regulation of nuclear-transcribed mRNA poly(A) tail shortening; IGI:SGD.
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; 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 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Endocytosis; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..1081
FT /note="Serine/threonine-protein kinase PKH2"
FT /id="PRO_0000086158"
FT DOMAIN 179..443
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 210..255
FT /note="PIF-pocket"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT REGION 494..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 805..833
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 970..1017
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..524
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..542
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 544..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 575..626
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 632..649
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 990..1017
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 303
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 189..191
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 208
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 258..260
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 264
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 307
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 321
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 1009
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
SQ SEQUENCE 1081 AA; 121660 MW; BE0DD9D49AC2EBC3 CRC64;
MYFDKDNSMS PRPLLPSDEQ KLNINLLTKK EKFSHLDPHY DAKATPQRST SNRNVGDLLL
EKRTAKPMIQ KALTNTDNFI EMYHNQQRKN LDDDTIKEVM INDENGKTVA STNDGRYDND
YDNNDINDQK TLDNIAGSPH MEKNRNKVKI EHDSSSQKPI AKESSKAQKN IIKKGIKDFK
FGSVIGDGAY STVMLATSID TKKRYAAKVL NKEYLIRQKK VKYVSIEKTA LQKLNNSPSV
VRLFSTFQDE SSLYFLLEYA PNGDFLSLMK KYGSLDETCA RYYAAQIIDA IDYLHSNGII
HRDIKPENIL LDGEMKIKLT DFGTAKLLNP TNNSVSKPEY DLSTRSKSFV GTAEYVSPEL
LNDSFTDYRC DIWAFGCILF QMIAGKPPFK ATNEYLTFQK VMKVQYAFTP GFPLIIRDLV
KKILVKNLDR RLTISQIKEH HFFKDLNFKD GSVWSKTPPE IKPYKINAKS MQAMPSGSDR
KLVKKSVNTL GKSHLVTQRS ASSPSVEETT HSTLYNNNTH ASTESEISIK KRPTDERTAQ
ILENARKGIN NRKNQPGKRT PSGAASAALA ASAALTKKTM QSYPTSSSKS SRSSSPATTS
RPGTYKRTSS TESKPFAKSP PLSASVLSSK VPMPPYTPPM SPPMTPYDTY QMTPPYTTKQ
QDYSDTAIAA PKPCISKQNV KNSTDSPLMN KQDIQWSFYL KNINEHVLRT EKLDFVTTNY
DILEKKMLKL NGSLLDPQLF GKPRHTFLSQ VARSGGEVTG FRNDPTMTAY SKTEDTYYSK
NIIDLQLLED DYRIEGGDLS ELLTNRSGEG YKCNQNSSPM KDDDKSESNN KGSSVFSGKI
KKLFHPTSAA ETLSSSDEKT KYYKRTIVMT SFGRFLVFAK RRQPNPVTNL KYELEYDINL
RQQGTKIKEL IIPLEMGTNH IVVIQTPYKS FLLSTDKKTT SKLFTVLKKI LNSNTNKIEK
ELLQRNQKVI ERRTSSSGRA IPKDLPTSKS PSPKPRTHSQ SPSISKHNSF SESINSAKSN
RSSRIFETFI NAKEQNSKKH AAPVPLTSKL VNGLPKRQVT VGLGLNTGTN FKNSSAKSKR
S
