ID SCH9_YEAST Reviewed; 824 AA.
AC P11792; D3DLF4;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 27-MAR-2024, entry version 221.
DE RecName: Full=Serine/threonine-protein kinase SCH9;
DE EC=2.7.11.1;
GN Name=SCH9; Synonyms=KOM1; OrderedLocusNames=YHR205W;
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=3290050; DOI=10.1101/gad.2.5.517;
RA Toda T., Cameron S., Sass P., Wigler M.;
RT "SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct
RT from, but functionally and structurally related to, cAMP-dependent protein
RT kinase catalytic subunits.";
RL Genes Dev. 2:517-527(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=JR26-19D;
RX PubMed=8442384; DOI=10.1002/yea.320090104;
RA di Blasi F., Carra E., de Vendittis E., Masturzo P., Burderi E.,
RA Lambrinoudaki I., Mirisola M.G., Seidita G., Fasano O.;
RT "The SCH9 protein kinase mRNA contains a long 5' leader with a small open
RT reading frame.";
RL Yeast 9:21-32(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
RN [4]
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 [5]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-723 AND SER-726, AND
RP IDENTIFICATION BY 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 [7]
RP FUNCTION, AND PHOSPHORYLATION AT THR-570; SER-711; THR-723; SER-726;
RP THR-737; SER-758 AND SER-765.
RX PubMed=17560372; DOI=10.1016/j.molcel.2007.04.020;
RA Urban J., Soulard A., Huber A., Lippman S., Mukhopadhyay D., Deloche O.,
RA Wanke V., Anrather D., Ammerer G., Riezman H., Broach J.R., De Virgilio C.,
RA Hall M.N., Loewith R.;
RT "Sch9 is a major target of TORC1 in Saccharomyces cerevisiae.";
RL Mol. Cell 26:663-674(2007).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-726, AND IDENTIFICATION BY
RP 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-723 AND SER-726, AND
RP 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 [11]
RP FUNCTION.
RX PubMed=20702584; DOI=10.1091/mbc.e10-03-0182;
RA Soulard A., Cremonesi A., Moes S., Schutz F., Jeno P., Hall M.N.;
RT "The rapamycin-sensitive phosphoproteome reveals that TOR controls protein
RT kinase A toward some but not all substrates.";
RL Mol. Biol. Cell 21:3475-3486(2010).
RN [12]
RP PHOSPHORYLATION.
RX PubMed=28483912; DOI=10.1128/mcb.00075-17;
RA Tanigawa M., Maeda T.;
RT "An In vitro TORC1 kinase assay that recapitulates the Gtr-independent
RT glutamine-responsive TORC1 activation mechanism on yeast vacuoles.";
RL Mol. Cell. Biol. 37:e00075-e00075(2017).
RN [13]
RP PHOSPHORYLATION.
RX PubMed=29698392; DOI=10.1371/journal.pgen.1007334;
RA Ukai H., Araki Y., Kira S., Oikawa Y., May A.I., Noda T.;
RT "Gtr/Ego-independent TORC1 activation is achieved through a glutamine-
RT sensitive interaction with Pib2 on the vacuolar membrane.";
RL PLoS Genet. 14:e1007334-e1007334(2018).
RN [14]
RP PHOSPHORYLATION, DISRUPTION PHENOTYPE, AND PHOSPHORYLATION AT THR-737.
RX PubMed=32801125; DOI=10.1242/jcs.245555;
RA Uemura S., Mochizuki T., Amemiya K., Kurosaka G., Yazawa M., Nakamoto K.,
RA Ishikawa Y., Izawa S., Abe F.;
RT "Amino acid homeostatic control by TORC1 in Saccharomyces cerevisiae under
RT high hydrostatic pressure.";
RL J. Cell Sci. 133:jcs245555-jcs245555(2020).
CC -!- FUNCTION: Protein kinase that is part of growth control pathway which
CC is at least partially redundant with the cAMP pathway. Regulates both
CC BCY1 phosphorylation and MPK1 activity (PubMed:20702584). Regulates
CC ribosome biogenesis, translation initiation, and entry into stationary
CC phase in a TORC1-dependent manner (PubMed:17560372).
CC {ECO:0000269|PubMed:17560372, ECO:0000269|PubMed:20702584}.
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: Activated by cAMP.
CC -!- PTM: Phosphorylated by TORC1 in nutrient-replete conditions and during
CC mechanical stress. {ECO:0000269|PubMed:28483912,
CC ECO:0000269|PubMed:29698392, ECO:0000269|PubMed:32801125}.
CC -!- DISRUPTION PHENOTYPE: Sensitive to high hydrostatic pressure
CC (mechanical stress); simultaneous disruption of RRD1 exacerbates the
CC effect. {ECO:0000269|PubMed:32801125}.
CC -!- MISCELLANEOUS: Present with 3850 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. cAMP subfamily. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB69735.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X12560; CAA31073.1; -; Genomic_DNA.
DR EMBL; X57629; CAA40853.1; -; Genomic_DNA.
DR EMBL; U00029; AAB69735.1; ALT_INIT; Genomic_DNA.
DR EMBL; BK006934; DAA06898.1; -; Genomic_DNA.
DR PIR; S48986; S48986.
DR RefSeq; NP_012075.1; NM_001179336.1.
DR AlphaFoldDB; P11792; -.
DR SMR; P11792; -.
DR BioGRID; 36639; 710.
DR ELM; P11792; -.
DR IntAct; P11792; 10.
DR MINT; P11792; -.
DR STRING; 4932.YHR205W; -.
DR iPTMnet; P11792; -.
DR MaxQB; P11792; -.
DR PaxDb; 4932-YHR205W; -.
DR PeptideAtlas; P11792; -.
DR EnsemblFungi; YHR205W_mRNA; YHR205W; YHR205W.
DR GeneID; 856612; -.
DR KEGG; sce:YHR205W; -.
DR AGR; SGD:S000001248; -.
DR SGD; S000001248; SCH9.
DR VEuPathDB; FungiDB:YHR205W; -.
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000168810; -.
DR HOGENOM; CLU_000288_52_2_1; -.
DR InParanoid; P11792; -.
DR OMA; SYAMGTT; -.
DR OrthoDB; 10768at2759; -.
DR BioCyc; YEAST:G3O-31231-MONOMER; -.
DR BRENDA; 2.7.11.1; 984.
DR Reactome; R-SCE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-SCE-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-SCE-165158; Activation of AKT2.
DR Reactome; R-SCE-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-SCE-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-SCE-203615; eNOS activation.
DR Reactome; R-SCE-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-SCE-389513; CTLA4 inhibitory signaling.
DR Reactome; R-SCE-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-SCE-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-SCE-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-SCE-6804757; Regulation of TP53 Degradation.
DR Reactome; R-SCE-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-SCE-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-SCE-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-SCE-9031628; NGF-stimulated transcription.
DR BioGRID-ORCS; 856612; 5 hits in 13 CRISPR screens.
DR PRO; PR:P11792; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P11792; Protein.
DR GO; GO:0000785; C:chromatin; IDA:SGD.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
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; IDA:SGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:1904828; P:positive regulation of hydrogen sulfide biosynthetic process; IMP:SGD.
DR GO; GO:0060963; P:positive regulation of ribosomal protein gene transcription by RNA polymerase II; IMP:SGD.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IMP:SGD.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IMP:SGD.
DR GO; GO:0008361; P:regulation of cell size; HMP:SGD.
DR GO; GO:1901494; P:regulation of cysteine metabolic process; IMP:SGD.
DR GO; GO:0032880; P:regulation of protein localization; IMP:SGD.
DR GO; GO:0047484; P:regulation of response to osmotic stress; IMP:SGD.
DR GO; GO:0090153; P:regulation of sphingolipid biosynthetic process; IMP:SGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:SGD.
DR CDD; cd05586; STKc_Sck1_like; 1.
DR CDD; cd11651; YPK1_N_like; 1.
DR Gene3D; 2.60.40.150; C2 domain; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351:SF245; AGC_AKT PROTEIN KINASE SCK2; 1.
DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 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; cAMP; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..824
FT /note="Serine/threonine-protein kinase SCH9"
FT /id="PRO_0000086638"
FT DOMAIN 166..378
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 412..671
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 672..748
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 125..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 285..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 285..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 538
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 418..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 441
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 570
FT /note="Phosphothreonine; by PKH1 or PKH2"
FT /evidence="ECO:0000269|PubMed:17560372"
FT MOD_RES 711
FT /note="Phosphoserine; by TORC1"
FT /evidence="ECO:0000269|PubMed:17560372"
FT MOD_RES 723
FT /note="Phosphothreonine; by TORC1"
FT /evidence="ECO:0000269|PubMed:17560372,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:19779198"
FT MOD_RES 726
FT /note="Phosphoserine; by TORC1"
FT /evidence="ECO:0000269|PubMed:17560372,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 737
FT /note="Phosphothreonine; by TORC1"
FT /evidence="ECO:0000269|PubMed:17560372,
FT ECO:0000305|PubMed:32801125"
FT MOD_RES 758
FT /note="Phosphoserine; by TORC1"
FT /evidence="ECO:0000269|PubMed:17560372"
FT MOD_RES 765
FT /note="Phosphoserine; by TORC1"
FT /evidence="ECO:0000269|PubMed:17560372"
FT CONFLICT 366
FT /note="I -> S (in Ref. 1; CAA31073)"
FT /evidence="ECO:0000305"
FT CONFLICT 751
FT /note="N -> K (in Ref. 1; CAA31073)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 824 AA; 91812 MW; BA84BE0F27143AB5 CRC64;
MMNFFTSKSS NQDTGFSSQH QHPNGQNNGN NNSSTAGNDN GYPCKLVSSG PCASSNNGAL
FTNFTLQTAT PTTAISQDLY AMGTTGITSE NALFQMKSMN NGISSVNNNN SNTPTIITTS
QEETNAGNVH GDTGGNSLQN SEDDNFSSSS TTKCLLSSTS SLSINQREAA AAAYGPDTDI
PRGKLEVTII EARDLVTRSK DSQPYVVCTF ESSEFISNGP ESLGAINNNN NNNNNNQHNQ
NQHINNNNEN TNPDAASQHH NNNSGWNGSQ LPSIKEHLKK KPLYTHRSSS QLDQLNSCSS
VTDPSKRSSN SSSGSSNGPK NDSSHPIWHH KTTFDVLGSH SELDISVYDA AHDHMFLGQV
RLYPMIHNLA HASQHQWHSL KPRVIDEVVS GDILIKWTYK QTKKRHYGPQ DFEVLRLLGK
GTFGQVYQVK KKDTQRIYAM KVLSKKVIVK KNEIAHTIGE RNILVTTASK SSPFIVGLKF
SFQTPTDLYL VTDYMSGGEL FWHLQKEGRF SEDRAKFYIA ELVLALEHLH DNDIVYRDLK
PENILLDANG NIALCDFGLS KADLKDRTNT FCGTTEYLAP ELLLDETGYT KMVDFWSLGV
LIFEMCCGWS PFFAENNQKM YQKIAFGKVK FPRDVLSQEG RSFVKGLLNR NPKHRLGAID
DGRELRAHPF FADIDWEALK QKKIPPPFKP HLVSETDTSN FDPEFTTAST SYMNKHQPMM
TATPLSPAMQ AKFAGFTFVD ESAIDEHVNN NRKFLQNSYF MEPGSFIPGN PNLPPDEDVI
DDDGDEDIND GFNQEKNMNN SHSQMDFDGD QHMDDEFVSG RFEI
//
