Classification of Saccharomyces cerevisiae
Protein Kinases

Tony Hunter & Gregory D. Plowman
TIBS 22:18-22, January 1997

(with links annotation by Christopher M. Smith)

The budding yeast protein kinases are subdivided into distinct families based on structural similarity in their catalytic domains. Individual kinases are listed by their preferred gene name as established by the Saccharomyces Genome Database at Stanford , followed by their synonyms and a brief description as maintained by in the Yeast Protein Database (YPD) available on the internet at http://www.proteome.com. Additional notes, sequence corrections, or close homologues, are in parentheses following each entry. Protein kinases preceded by an asterisk share only weak similarity to other members. Entries listed as misclassified kinases are flagged as protein kinases in YPD, but have no structural similarity to the protein kinase family and were excluded from this analysis (some of these represent non-catalytic regulatory domains). Three additional open reading frames were identified that encode protein kinases that were not present in the YPD listing: YPL150W (Group IIB), YMR216C (Group IIID), and YPL2 36C (Group VII). These new protein kinases were recognized following a comprehensive analysis of the complete yeast DNA sequence using the MPSRCH software (Oxford Molecular) implementation of the Smith Waterman algorithm on a Maspar parallel computer.

I. AGC Group - (17 members)

A. PKA-family: cAMP-dependent (Similar to PKA_h)
TPK1 (M17072)/PKA1/SRA3/PK25 (125298)/J0541 /YJL164C cAMP-dependent protein kinase 1, catalytic subunit.
TPK2 (M17073)/Y00694/PKA2/YKR1/P1855/YPL203W cAMP-dependent protein kinase 2, catalytic subunit.
TPK3 (M17074)/PKA3/YKL630/YKL166C/D28151 cAMP-dependent protein kinase 3, catalytic subunit.

B. PKC-family: DAB-activated, PL-dependent (Similar to PKC_h)
PKC1 (M32491)/STT1/HPO2/CLY15/YBL0807/YBL105C Protein kinase C; regulates MAP kinase cascade involved in regulating cell wall metabolism.

C. AGC-family (Similar to SCK1_sp, RACa_h, AKT_h - no diacylglycerol binding domain)
SCH9 (X12560)/KOM1/YHR205W Serine/threonine protein kinase that is activated by cAMP; overproduction can suppress cdc25 mutant.
YPK1 (M21307)/YKL126W (Z28126) Serine/th reonine protein kinase with similarity to protein kinase C.
YPK2 (Z49702)/YKR2/YM9718.03/YMR104C Serine/threonine protein kinase with similarity to Ypk1p.

D. S6K (70 kDa)-family (Similar to KAD5_sp, SGK_r)
KIN82/YCR1153/YCR091W Serine/threonine protein kinase of unknown function.
YNR047W (Z71662)/N3449 Serine/threonine protein kinase of unknown function.

E. DBF2-family (Similar to KAIB_sp, NDR_h)
DBF2/G4643/YGR092W/M34146 Serine/threonine protein kinase similar to Dbf20p; required for events in anaphase/telophase.
DBF20/P8283.6/YPR111W Cell cycle protein kinase similar to Dbf2p; involved in termination of M-phase.

F. PKA-related-family (unique to S. cerevisiae)
YOL100W/HRC1081/O0784 Serine/threonine protein kinase of unknown function.
YDR490C/D8035.33 Serine/threonine protein kinase of unknown function
YDR466W/D8035.10 Serine/threonine protein kinase of unknown function.

G. Other AGC-family (Similar to CEK1_sp, COT1_nc, NDR_h, LATS_dm, MAST205_m)
YFL033C Serine/threonine protein kinase with similarity to S. pombe CEK1 protein kinase.
YNL161W/N1727 Putative serine/threonine protein kinase of unknown function.
*YBR028C/YBR0312 Serine/threonine protein kinase with similarity to Ypk2p/Ykr2p and Ypk1p.

II. CaMK Group - (16 members)

A. CaMK-family: Ca/calmodulin regulated (Similar to CaMKI_h)
CMK1/YFR014C Calcium/calmodulin-dependent serine/threonine protein kinase (CaM kinase), type I.
CMK2/O2325/YOL016C Calcium/calmodulin-dependent serine/threonine protein kinase (CaM kinase), type II.
RCK1/G1854/YGL158W Serine/threonine protein kinase with similarity to Cmk1p, Cmk2p, and Cmk3p. (Sequence updated)
RCK2/CMK3/CLK1/L9672.6/YLR248W Calcium/calmodulin-dependent serine/threonine protein kinase (CaM kinase).

B. SNF1/AMPK-family (Similar to AMPK_h, NPK5_nt, PAR1_ce)
SNF1/CAT1/CCR1/PAS14/HAF3/D8035.20/YDR477W Serine/threonine protein kinase essential for derepression of glucose-repressed genes; acts with Snf4p .
KIN1/YD9727.17/YDR122W Serine/threonine protein kinase; similar to Kin2p and S. pombe KIN1.
KIN2/L8004.3/L2546/YLR096W Serine/threonine protein kinase; similar to Kin1p and S. pombe KIN1.
KIN4/KIN31/(KIN3)/O5220/YOR233W Serine/threonine protein kinase; similar to Kin1p and Kin2p; catalytic domain is most similar to Snf1p.
YPL141C/LPI5 Serine/threonine protein kinase with similarity to Kin4p.
YPL150W/P2597 Serine/threonine protein kinase of unknown function. (Not in YPD listing)

C. GIN4-family (Similar to SNF1_sc)
GIN4/D9719.13/YDR507C Serine/threonine-protein kinase with similarity to Yc1024p; growth inhibitory protein.
YCL024W Protein with similarity to Snf1p.
HSL1/YKL453/YKL101W Serine/threonine protein kinase that interacts genetically with histone mutations.

D. Other CaMK-family (Similar to Z71478_sp, MLCK_dd, CaMKI_h)
MEK1/MRE4/O6357/YOR351C Serine/threonine protein kinase required for meiotic recombination; contains forkhead-associated (FHA) nuclear signalling domain.
DUN1/ORF2370/YDL101C Protein kinase necessary for induction of Rnr3p and DNA repair genes after DNA damage; contains FHA domain.
*YMR291W/ORF530348 Serine/threonine protein kinase of unknown function.

III. CMGC Group - (21 members)

A. CDK-family (Similar to CDK2_h)
CDC28/CDK1/SRM5/HSL5/YBR1211/YBR160W Cyclin-dependent protein kinase essential for completion of START and for mitosis; associates with Cks1p and cyclins. PSTAIRE in kinase subdomain III.
PHO85/P7102_18A/YPL031C Cyclin-dependent protein kinase that interacts with cyclin Pho80p to regulate phosphate pathway. PSTAIRE in kinase subdomain III.
CAK1/CIV1/ YFL029C Cdk-activating kinase (serine/threonine protein kinase) responsible for in vivo activation of Cdc28p. PHNAKFE in kinase subdomain III.
SSN3/UME5/SRB10/(ARE1)/P7102_08/YPL042C Cyclin-dependent serine/threonine protein kinase of the RNA polymerase II holoenzyme complex and Kornberg's mediator (SRB) subcomplex. SQSACRE in kinase subdomain III. TLY in kinase subomain VIII.
KIN28/ORF2330/YDL108W Cyclin-dependent serine/threonine protein kinase component of transcription initiation factor TFIIH; phosphorylates C-terminal domain (CTD) of RNA polymerase large subunit. DMSAIRE in kinase subdomain III.

B. MAPK-family (Similar to SPK1_sp, ERK_h)
KSS1/G4149/YGR040W Serine/threonine protein kinase of the MAP kinase family (MAPK); redundant with Fus3p for induction of mating specific genes by mating pheromone. TEY in kinase subdomain VIII (activation loop).
FUS3/DAC2/YBL0303/YBL03.21/YBL016W Serine/threonine protein kinase of the MAP kinase family required for cell cycle arrest and for cell fusion during mating. TEY in kinase subdomain VIII.
HOG1/SSK3/L9354.2/L2931/YLR113W Serine/threonine protein kinase of MAP kinase family; involved in high-osmolarity signal transduction pathway. TGY in kinase subdomain VIII.
SLT2/MPK1/SLK2/BYC2/YHR030C Serine/threonine protein kinase of MAP kinase family involved in the cell wall integrity pathway. TEY in kinase subdomain VIII.
YKL161C/YKL615 Serine/threonine protein kinase of unknown function. KGY in kinase subdomain VIII.
SMK1/YP9499.10/YPR048W Sporulation-specific MAP kinase required for completion of sporulation. TNY in kinase subdomain VIII.

C. GSK3-family (Similar to SHAGGY_dm, GSK3_h)
MCK1/(YPK1)/N0392/YNL307C Serine/threonine/tyrosine protein kinase (meiosis and centromere regulatory kinase); positive regulator of meiosis and spore formation.
YOL128C/O0530/ORF1209713 Protein serine/threonine protein kinase of unknown function.
MDS1/RIM11/GSK3/YM9375.08/YMR139W Serine/threonine protein kinase; homologue of mammalian GSK3.
MRK1/D2459/D2461/YDL079C Serine/threonine protein kinase with similarity to Mds1p.

D. CLK-family
KNS1/L1224/YLL019C Serine/threonine protein kinase of unknown function. (Similar to CLK_h)
YAK1/YJL141C Serine/threonine protein kinase that suppresses loss of Tpk1p + Tpk2p + Tpk3p. (Similar to KA23_sp, MNB_dm, MNB_h)
YMR216C/YM8261.10 Putative serine/threonine protein kinase; has similarity to Cdc31p. (Similar to DSK1_sp, SRPK1_ce, U52111_h). (Not in YPD listing)
IME2/SME1/J0817/YJL106W Serine/threonine protein kinase and positive regulator of sporulation genes that is essential for initiation of meiosis. TAY in kinase subdomain VIII (activation loop). (Similar to MAK_r, p34_h, CDK2_h)

E. Other CMGC-family (Similar to PITSLRE_h, CHED_h)
SGV1/BUR1/P9584.8/YPR161C Serine/threonine protein kinase involved in pheromone adaptation pathway and in cell cycle. PITAQRE in kinase subdomain III.
CTK1/YKL139W Carboxyl-terminal domain (CTD) kinase a subunit; cyclin dependent protein kinase that phosphorylates C-terminal domain of RNA polymerase II large subunit. PITSIRE in kinase subdomain III.

IV. STE11/STE20 Group - (10 members)

A. STE11/MEKK-family (Similar to BYR2_sp, NPK1_nt, MEKK_h)
STE11/L8039.10/YLR362W Serine/threonine protein kinase of the MEKK family; component of the pheromone pathway and a pathway regulating filamentous growth.
BCK1/(SLK1)/SSP31/LAS3/SAP3/J0906/YJL095W Serine/threonine protein kinase of the MEKK family; involved in the cell wall integrity pathway.
SSK2/N3276/YNR031C MAP kinase kinase kinase of the high osmolarity signal transduction pathway.
SSK22/YCR073C MAP kinase kinase kinase with strong similarity to Ssk2p; participates in the high osmolarity signal transduction pathway.

B. STE20/PAK-family (Similar to PAK_dm, PAK1_h, PAK65_h, RAC_h)
STE20/YHL007C Serine/threonine protein kinase in the pheromone pathway; also participates in pathway regulating filamentous growth.
CLA4/ERC10/N0450/YNL0450/YNL298W Serine/threonine protein kinase required for cytokinesis; has similarity to Ste20p.
YOL113W/HRA655/O0722 Serine/threonine protein kinase with similarity to Ste20p.

C. NRK/MESS-family (Similar to MESS1_m, ZC504.4_ce)
NRK1/KIC1/H8263.14/YHR102W Serine/threonine protein kinase that interacts with Cdc31p.
SPS1/D9719.27/YDR523C Serine/threonine protein kinase involved in middle/late stage of meiosis.
*CDC15/YAR019C Protein kinase of the MAP kinase kinase kinase family essential for late nuclear division. (Similar to MESS1_m, CDC7_sp, MST1_h)

V. STE7/MEK Group - (8 members)

A. STE7-family (Similar to HST7_ce, MEK1_h)
STE7/D1525/YDL159W Serine/threonine/tyrosine protein kinase of MAP kinase kinase (MEK) family; component of the pheromone pathway and a pathway regulating filamentous growth.
PBS2/HOG4/SFS4/SSK4/OSR1/J0699/YJL128C Serine/threonine/tyrosine protein kinase of the MAP kinase kinase (MEK kinase) family; essential component of the high-osmolarity signal transduction pathway.
MKK1/SSP32/O5095/YOR231W Serine/threonine/tyrosine protein kinase of the MAP kinase kinase (MEK) family involved in cell wall integrity pathway.
MKK2/SSP33/LPI6/YPL140C Serine/threonine/tyrosine protein kinase of the MAP kinase kinase (MEK) family involved in cell wall integrity pathway. (Sequence updated)

B. NIMA/NEK-family (Similar to NIMA_en, NIMA1_h, NEK1_h)
KIN3/NPK1/FUN52/YAR018C Serine/threonine protein kinase; null mutation has no phenotype. TTY in kinase subdomain VIII (activation loop).

C. NEK-like-family (Similar to F35G12.3_ce, weakly to NEK1_h)
YNL020C/N2823 Serine/threonine protein kinase of unknown function.
YIL095W/(PAK1) Serine/threonine protein kinase of unknown function.
YBR059C/YBR0419 Serine/threonine protein kinase of unknown function.

VI. OTHER Group - (24 members)

A. Casein kinase I-family (Similar to CKI_h)
YCK1/CKI2/YHR135C Casein kinase I isoform.
YCK2/(CKI1)/(CKI)/N1755/YNL154C Casein kinase I isoform.
YCK3/CKI3/YER123W Casein kinase I isoform.
HRR25/P1850/YPL204W Casein kinase I, serine/threonine/tyrosine protein kinase; associated with DNA repair and meiosis.

B. Casein kinase II-family (Similar to CKA2_h)
CKA1/YIL035C Casein kinase II, catalytic (a) subunit.
CKA2/O2810/YOR061W Casein kinase II, catalytic (a) subunit.
*CDC7/SAS1/OAF2/D2855/YDL017W Protein kinase required for initiation of DNA synthesis, for commitment to sporulation, for DNA repair, and for meiotic recombination. (Similar to HSK1_sp)

C. NPR/HAL5-family (unique to S. cerevisiae)
HAL5/J0531/YJL165C Serine/threonine protein kinase involved in salt and pH tolerance.
YKL168C/YKL632 Serine/threonine protein kinase of unknown function.
SAT4/YCR101/YCR046/YCR008W Protein with similarity to Npr1p protein kinase.
YJR059W/J1725 Putative serine/threonine protein kinase of unknown function.
PTK1/YKL198C Serine/threonine protein kinase that enhances spermine uptake. (Frame shift corrected)
NPR1/N1631/YNL183C Serine/threonine protein kinase involved in regulating transport systems for nitrogen nutrients under conditions of nitrogen catabolite derepression.
YDL214C/D1014 Serine/threonine protein kinase with similarity Npr1.
YDL025C/D2810 Protein with similarity to protein kinase Npr1p.
YOR267C/O5420 Serine/threonine kinase protein kinase with similarity to Npr1p.

D. ELM-family (unique to yeast, Similar to D45882_sp)
PAK1/SYGP-ORF45/YER129W Protein kinase capable of suppressing DNA polymerase a mutations.
YGL179C/BIE560/G1618 Serine/threonine protein kinase with similarity to Elm1p and Kin82p.
ELM1/YKL261/YKL048C Serine/threonine protein kinase regulating pseudohyphal growth.

E. RAN-family (Similar to RAN_sp, p78_h)
SHA3/SKS1/LPB5/YPL026C Serine/threonine protein kinase; suppressor of hta1 mutations that cause aberrant transcription.
YDR247W/YD8419.14 Serine/threonine protein kinase with similarity to S. pombe RAN1 negative regulator of sexual conjugation and meiosis.
*KSP1/YHR082C Serine/threonine kinase with similarity to casein kinase II.

F. PIM-like-family (Similar to PIM2_m, KIAA0135_h)
*YAL017W/YAL002/FUN31 Serine/threonine protein kinase of unknown function.
*YOL045W/02034/YOL044W Serine/threonine protein kinase of unknown function.

VII. Unique Kinases - (17 members) (No Similar S. cerevisiae kinases)

A. Kinases with possible homologues in other species
*CDC5/PKX2/MSD2/YM8270.03/YMR001C Serine/threonine protein kinase required for exit from mitosis; ts mutants block after nuclear division. (Similar to PLK-1_h, POLO_dm)
*IPL1/P1820/YPL209C Serine/threonine protein kinase involved in chromosome segregation. (Similar to AUR_dm)
*IRE1/ERN1/YHR079C Protein kinase and type I membrane protein involved in signal transduction from ER lumen to nucleus; part of the unfolded protein response. (Similar to C41C4.4_ce)
*VPS15/VPT15/(VPL19)/YBR0825/YBR097W Serine/threonine protein kinase involved in vacuolar protein sorting. (Similar to ZK930.1_ce)
*YPL236C/P1057 Protein of unknown function. - No GXG (Similar to C3H1.13_sp) (Not in YPD)
*YGL180W/G1615 Serine/threonine protein kinase of unknown function. (Similar to UNC-51_ce, PLO1_sp)
*SWE1/J0406/YJL187C Serine/tyrosine dual-specificity protein kinase able to phosphorylate Cdc28p on tyrosine and inhibit its activity. (Similar to Wee1_sp, and MLK_h)
*SPK1/RAD53/MEC2/SAD1/P2588/YPL153C Serine/threonine/tyrosine protein kinase with a checkpoint function in S and G2. Contains FHA domain. (Similar to CDS1_sp)
*MPS1/RPK1/D2785/YDL028C Serine/threonine/tyrosine protein kinase involved in spindle pole body duplication (Similar to ESK_m, TTK_h).
*YKL116C/YKL516 Serine/threonine protein kinase with similarity to S pombe NIM1 protein kinase. (33% Identity to p78_h)
*GCN2/AAS1/D9954.16/YDR283C Serine/threonine protein kinase that regulates initiation of translation by phosphorylation of eIF2a (Sui2p) (Similar to EIF2aK_r, HRI_r)
*YBR274W/YBR1742 Protein kinase with similarity to members of the growth factor and cytokine receptor family. (Similar to CHK1-sp, CHK1_ce, SNF1_r)
*YGR262C/G9334 Protein with similarity to apple tree calcium/calmodulin-binding protein kinase PIR:JQ2251. Lacks GXG - not in alignment (Similar to O-sialoglycoprotein endopeptidase from Methanococcus jannaschii)

B. Kinases without known homologue
*BUB1/G7542/YGR188C Serine/threonine protein kinase and checkpoint protein required for cell cycle arrest in response to loss of microtubule function. (N-terminus Similar to MAD3_sc)
*YKL171W/YKL635 Serine/threonine protein kinase of unknown function. (Similar to none)
*YGR052W/G4329 Protein of unknown function. (Similar to none)
*YPR106W/P8283.9 Protein with similarity to protein kinases Gcn2p; galactosyltransferase-associated protein kinase P58/Gtap, and the Raf proto-oncoprotein. (Similar to none)

VII. Atypical Protein Kinases - (1 member)

Miscellaneous Protein Kinases
*YGR080W/G4583 Protein with similarity to human tyrosine kinase A6 PIR:A55922.

PI-Kinases
TOR1/DRR1/J1803/YJR066W Phosphatidylinositol kinase(PI kinase) homologue involved in cell growth and sensitivity to the immunosuppressant rapamycin.
TOR2/DRR2/YKL203C Phosphatidylinositol kinase(PI kinase) homologue involved in cell growth and sensitivity to the immunosuppressant rapamycin, similar to Tor1p.
VPS34/VPT29/(VPL7)/END12/L9672.10/YKR240W Phosphatidylinositol 3-kinase required for vacuolar protein sorting; activated by protein kinase Vps15p.
PIK1/PIK41/PIK120/N0795/YNL267W Phosphatidylinositol 4-kinase; generates PtdIns 4-P.
STT4/L2142.4/YLR305C Phosphatidylinositol-4-kinase; mutants are staurosporine-sensitive and suppressible by overexpression of Pkc1p.
MEC1/ESR1/SAD3/YBR1012/YBR136W Checkpoint protein required for mitotic growth; DNA repair and mitotic recombination (PI kinase homologue).
TEL1/YBL0706/YBL088C Protein involved in controlling telomere length; may have phosphatidylinositol 3-kinase or protein kinase activity.
YHR099W Protein with weak similarity to Tor1p and Tor2p; possible phosphatidylinositol kinase (PI kinase) homologue.
FAB1/YFR019W Probable PIP 5-kinase involved in orientation or separation of mitotic chromosomes.
MSS4/YD8142A.05/YD8142.05 Potential PIP 5-kinase; multicopy suppressor of stt4 mutation.

Guanylate Kinases
GUK1/D9461.39/YDR454C Guanylate kinase.

Histidine Protein Kinases
SLN1/YPD2/YIL147C Two-component signal transducer with both a histidine kinase domain and a receiver domain that functions in the high osmolarity signal transduction pathway.
YIL042C Related to the mitochondrial branched-chain a-ketoacid (BKCD) and pyruvate dehydrogenase (PDH) kinases, which are protein-serine kinases

Misclassified Kinases
MSS2/D2340/YDL107W/ORF2340 Involved in the expression of mitochondrial cytochrome C oxidase subunit 2 (COX2). (Serine/threonine protein kinase that suppresses the growth defect of snf3 mutants on low glucose.)
YDR109C/YD9727.05 Protein with similarity to FGGY protein kinase family.
YJR061W Putative serine/threonine protein kinase of unknown function. (Similar to YKL200c_sc, YKL201c_sc)
YLR063W/L2174 Serine/threonine protein kinase of unknown function (Unique)
YML059C/YM9958.03 Protein kinase of unknown function (Similar to ZK370.4_ce, M110.7_ce)
YMR192W/YM9646.04 Serine/threonine protein kinase of unknown function. (Leucine repeat and possible coiled coil - Similar to YPL249C_sc, U49940_ce)
YGL059W/G3441 Protein with similarity to Rat branched-chain a-ketoacid dehydrogenase kinase PIR:U27456.
YGL227W/G0958 Protein with similarity to Dictyostelium discoideum non-receptor tyrosine kinase U32174. 37% ID over 64 aa in N-terminal non-catalytic domain.
YOR287C/O5492 Protein with weak similarity to PITSLRE protein kinase isoforms