STE20_SCHPO
ID STE20_SCHPO Reviewed; 658 AA.
AC P50527;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Serine/threonine-protein kinase shk1/pak1;
DE EC=2.7.11.1;
GN Name=shk1; Synonyms=orb2, pak1, ste20; ORFNames=SPBC1604.14c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CDC42, AND FUNCTION.
RX PubMed=8846783; DOI=10.1002/j.1460-2075.1995.tb00278.x;
RA Ottilie S., Miller P.J., Johnson D.I., Creasy C.L., Sells M.A.,
RA Bagrodia S., Forsburg S.L., Chernoff J.;
RT "Fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p
RT and is involved in the control of cell polarity and mating.";
RL EMBO J. 14:5908-5919(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Marcus S.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 119-658, INTERACTION WITH CDC42, AND
RP FUNCTION.
RX PubMed=7597098; DOI=10.1073/pnas.92.13.6180;
RA Marcus S., Polverino A., Chang E., Robbins D., Cobb M.H., Wigler M.;
RT "Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65PAK
RT protein kinases, is a component of a Ras/Cdc42 signaling module in the
RT fission yeast Schizosaccharomyces pombe.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:6180-6184(1995).
RN [5]
RP FUNCTION, AND INTERACTION WITH SKB1.
RX PubMed=8943016; DOI=10.1073/pnas.93.24.13802;
RA Gilbreth M., Yang P., Wang D., Frost J., Polverino A., Cobb M.H.,
RA Marcus S.;
RT "The highly conserved skb1 gene encodes a protein that interacts with Shk1,
RT a fission yeast Ste20/PAK homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:13802-13807(1996).
RN [6]
RP FUNCTION, AND INTERACTION WITH CDC42.
RX PubMed=9843966; DOI=10.1073/pnas.95.25.14781;
RA Gilbreth M., Yang P., Bartholomeusz G., Pimental R.A., Kansra S.,
RA Gadiraju R., Marcus S.;
RT "Negative regulation of mitosis in fission yeast by the shk1 interacting
RT protein skb1 and its human homolog, Skb1Hs.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14781-14786(1998).
RN [7]
RP FUNCTION.
RX PubMed=10574765; DOI=10.1016/s0960-9822(00)80058-5;
RA Sawin K.E., Hajibagheri M.A.N., Nurse P.;
RT "Mis-specification of cortical identity in a fission yeast PAK mutant.";
RL Curr. Biol. 9:1335-1338(1999).
RN [8]
RP INTERACTION WITH SKB5.
RX PubMed=10593886; DOI=10.1074/jbc.274.51.36052;
RA Yang P., Pimental R.A., Lai H., Marcus S.;
RT "Direct activation of the fission yeast PAK Shk1 by the novel SH3 domain
RT protein, Skb5.";
RL J. Biol. Chem. 274:36052-36057(1999).
RN [9]
RP INTERACTION WITH SCD2, AND AUTOPHOSPHORYLATION.
RX PubMed=10567532; DOI=10.1128/mcb.19.12.8066;
RA Chang E., Bartholomeusz G., Pimental R.A., Chen J., Lai H., Wang L.L.,
RA Yang P., Marcus S.;
RT "Direct binding and In vivo regulation of the fission yeast p21-activated
RT kinase shk1 by the SH3 domain protein scd2.";
RL Mol. Cell. Biol. 19:8066-8074(1999).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11972773; DOI=10.1046/j.1365-2958.2002.02882.x;
RA Qyang Y., Yang P., Du H., Lai H., Kim H., Marcus S.;
RT "The p21-activated kinase, Shk1, is required for proper regulation of
RT microtubule dynamics in the fission yeast, Schizosaccharomyces pombe.";
RL Mol. Microbiol. 44:325-334(2002).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF TEA1.
RX PubMed=12764130; DOI=10.1074/jbc.m302609200;
RA Kim H., Yang P., Catanuto P., Verde F., Lai H., Du H., Chang F., Marcus S.;
RT "The kelch repeat protein, Tea1, is a potential substrate target of the
RT p21-activated kinase, Shk1, in the fission yeast, Schizosaccharomyces
RT pombe.";
RL J. Biol. Chem. 278:30074-30082(2003).
RN [12]
RP INTERACTION WITH RGA8.
RX PubMed=14506270; DOI=10.1074/jbc.m306819200;
RA Yang P., Qyang Y., Bartholomeusz G., Zhou X., Marcus S.;
RT "The novel Rho GTPase-activating protein family protein, Rga8, provides a
RT potential link between Cdc42/p21-activated kinase and Rho signaling
RT pathways in the fission yeast, Schizosaccharomyces pombe.";
RL J. Biol. Chem. 278:48821-48830(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301 AND SER-303, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
CC -!- FUNCTION: MAP4K component of the MAPK pathway required for the mating
CC pheromone response. Phosphorylates histone H2B to form H2BS10ph (By
CC similarity). Phosphorylates tea1. Required for skb1-dependent mitotic
CC inhibitory function. Regulates microtubule dynamics and cell polarity.
CC {ECO:0000250, ECO:0000269|PubMed:10574765, ECO:0000269|PubMed:11972773,
CC ECO:0000269|PubMed:12764130, ECO:0000269|PubMed:7597098,
CC ECO:0000269|PubMed:8846783, ECO:0000269|PubMed:8943016,
CC ECO:0000269|PubMed:9843966}.
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: Forms an activated complex with GTP-bound ras-like cdc42.
CC Interacts with skb1 and the SH3 domain of skb5 via its amino-terminal
CC regulatory domain. Skb1, cdc42 and shk1 are able to form a ternary
CC complex in vivo. Interacts with rga8 and may interact with byr2.
CC {ECO:0000269|PubMed:10567532, ECO:0000269|PubMed:10593886,
CC ECO:0000269|PubMed:14506270, ECO:0000269|PubMed:7597098,
CC ECO:0000269|PubMed:8846783, ECO:0000269|PubMed:8943016,
CC ECO:0000269|PubMed:9843966}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11972773}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:11972773}.
CC Note=Localizes at cell ends, septum forming regions and at the mitotic
CC spindle.
CC -!- PTM: Autophosphorylated on serine residues.
CC {ECO:0000269|PubMed:18257517}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U22371; AAC49125.1; -; mRNA.
DR EMBL; L41552; AAB52609.1; -; Genomic_DNA.
DR EMBL; CU329671; CAA22347.1; -; Genomic_DNA.
DR PIR; S60170; S60170.
DR PIR; T39500; T39500.
DR RefSeq; NP_596626.1; NM_001022547.2.
DR AlphaFoldDB; P50527; -.
DR SMR; P50527; -.
DR BioGRID; 276541; 24.
DR DIP; DIP-949N; -.
DR IntAct; P50527; 1.
DR MINT; P50527; -.
DR STRING; 4896.SPBC1604.14c.1; -.
DR iPTMnet; P50527; -.
DR MaxQB; P50527; -.
DR PaxDb; P50527; -.
DR PRIDE; P50527; -.
DR EnsemblFungi; SPBC1604.14c.1; SPBC1604.14c.1:pep; SPBC1604.14c.
DR GeneID; 2539997; -.
DR KEGG; spo:SPBC1604.14c; -.
DR PomBase; SPBC1604.14c; shk1.
DR VEuPathDB; FungiDB:SPBC1604.14c; -.
DR eggNOG; KOG0578; Eukaryota.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; P50527; -.
DR OMA; IEISTPY; -.
DR PhylomeDB; P50527; -.
DR BRENDA; 2.7.11.1; 5613.
DR Reactome; R-SPO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-SPO-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-SPO-5627123; RHO GTPases activate PAKs.
DR Reactome; R-SPO-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-SPO-9013405; RHOD GTPase cycle.
DR Reactome; R-SPO-9013420; RHOU GTPase cycle.
DR Reactome; R-SPO-9013424; RHOV GTPase cycle.
DR PRO; PR:P50527; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0071521; C:Cdc42 GTPase complex; IPI:PomBase.
DR GO; GO:0032153; C:cell division site; IDA:PomBase.
DR GO; GO:0051286; C:cell tip; IDA:PomBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0110085; C:mitotic actomyosin contractile ring; IDA:PomBase.
DR GO; GO:0120105; C:mitotic actomyosin contractile ring, intermediate layer; IDA:PomBase.
DR GO; GO:0005876; C:spindle microtubule; IDA:PomBase.
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:PomBase.
DR GO; GO:0007015; P:actin filament organization; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:1903472; P:negative regulation of mitotic actomyosin contractile ring contraction; IMP:PomBase.
DR GO; GO:0061161; P:positive regulation of establishment of bipolar cell polarity regulating cell shape; IGI:PomBase.
DR GO; GO:2000247; P:positive regulation of establishment or maintenance of bipolar cell polarity regulating cell shape; IMP:PomBase.
DR GO; GO:0062038; P:positive regulation of pheromone response MAPK cascade; IMP:PomBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IGI:PomBase.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR Gene3D; 3.90.810.10; -; 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; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR011026; WASP_C.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47912; SSF47912; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 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; Cytoskeleton; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..658
FT /note="Serine/threonine-protein kinase shk1/pak1"
FT /id="PRO_0000086651"
FT DOMAIN 147..160
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 386..637
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 505
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 392..400
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 415
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT CONFLICT 492..495
FT /note="GLQH -> LYSD (in Ref. 1; AAC49125)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="R -> P (in Ref. 1; AAC49125)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 658 AA; 72358 MW; 69D72E5C925021E5 CRC64;
MERGTLQPRK KAPNGYGITP IVAHKTGEPV RYEVEDDLRK LKPSRTAPKP PAINTNLAED
TFSGFPLSQS RTTVSRVSLG SRQHSSSSIR KLQTNVSDVR SYDERNQKKS AFENFVSSMS
SFLTGGGSSP TSSYGSGSAS PRKSTVISSP FDPKHVTHVG FNYDTGEFTG MPTEWQALLK
VSGITKSEQV QHPQAVLDAM AFYSQSKKYL EEGAKPPFPR ESTEKPLLSV SALSSSSHLQ
PTSATSSSSR LYPSRPAPTP PASSSSSPLL SSQTVKTTTS NASRQPSPLV SSKSTDNIIR
SHSPVLLTPQ TLSTSETKHI RPNNSTPYQR RAETSTKPKA VATPQKVEAP SAPRLQKRAP
RQQSNDSAVL AKLQSICNPK NPTLLYRNFV KIGQGASGDV YSARQVGTNL SVAIKKMNIN
QQPKKEFIVN EILVMKSHHH KNIVNFIDTF FYKSELWMVM EYMRGGSLTE VVTNNTLSEG
QIAAICKETL EGLQHLHENG IVHRDIKSDN ILLSLQGDIK LTDFGFCAQI DSNMTKRTTM
VGTPYWMAPE VVTRKEYGFK VDVWSLGIMA IEMVEGEPPY LNENPLRALY LIATIGTPKI
SRPELLSSVF HDFLSKSLTV NPKQRPSSGE LLRHPFLKQA VPVSSLIPLI KSIHHSGK
