PAKC_DICDI
ID PAKC_DICDI Reviewed; 477 AA.
AC Q55GV3; Q9NAY0;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Serine/threonine-protein kinase pakC {ECO:0000303|PubMed:15483055};
DE Short=dPAKc;
DE EC=2.7.11.1;
GN Name=pakC; ORFNames=DDB_G0267450;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, INTERACTION WITH
RP RACB, SUBCELLULAR LOCATION, PHOSPHOLIPID-BINDING, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-33; HIS-120; HIS-123; LEU-143;
RP LYS-233; SER-465 AND PRO-469.
RX PubMed=15483055; DOI=10.1091/mbc.e04-04-0323;
RA Lee S., Rivero F., Park K.C., Huang E., Funamoto S., Firtel R.A.;
RT "Dictyostelium PAKc is required for proper chemotaxis.";
RL Mol. Biol. Cell 15:5456-5469(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF82310.3}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA de la Roche M.A., Cote G.P.;
RT "Dictyostelium discoideum PAK-like kinase fragment.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Has role in the regulation of chemotaxis.
CC {ECO:0000269|PubMed:15483055}.
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:0000269|PubMed:15483055};
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:0000269|PubMed:15483055};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15483055};
CC -!- ACTIVITY REGULATION: Kinase activity is rapidly and transiently
CC increased in response to chemoattractant stimulation.
CC {ECO:0000269|PubMed:15483055}.
CC -!- SUBUNIT: Interacts with GTP-bound racB. {ECO:0000269|PubMed:15483055}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15483055}. Membrane
CC {ECO:0000269|PubMed:15483055}. Note=Cytosolic in unstimulated cells,
CC localizes to the plasma membrane in response to chemoattractant
CC stimulation with kinetics consistent with those of kinase activation,
CC where it binds to phospholipids via its PH domain.
CC {ECO:0000269|PubMed:15483055}.
CC -!- DEVELOPMENTAL STAGE: Preferentially expressed during vegetative growth
CC and in the earliest stages of development. Expressed at significantly
CC lower levels during later stages of development.
CC {ECO:0000269|PubMed:15483055}.
CC -!- DISRUPTION PHENOTYPE: Cells are less-polarized than wild-type and are
CC unable to properly regulate the direction of pseudopod formation,
CC resulting in a reduction in the distance traveled in response to
CC chemoattractant. {ECO:0000269|PubMed:15483055}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000269|PubMed:15483055}.
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DR EMBL; AF277804; AAF82310.3; -; mRNA.
DR EMBL; AAFI02000003; EAL73178.2; -; Genomic_DNA.
DR RefSeq; XP_647081.2; XM_641989.2.
DR AlphaFoldDB; Q55GV3; -.
DR SMR; Q55GV3; -.
DR IntAct; Q55GV3; 1.
DR STRING; 44689.DDB0267078; -.
DR PaxDb; Q55GV3; -.
DR GeneID; 8615885; -.
DR KEGG; ddi:DDB_G0267450; -.
DR dictyBase; DDB_G0267450; pakC.
DR eggNOG; KOG0578; Eukaryota.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q55GV3; -.
DR OMA; IMMMEMA; -.
DR PhylomeDB; Q55GV3; -.
DR Reactome; R-DDI-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-DDI-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-DDI-3928662; EPHB-mediated forward signaling.
DR Reactome; R-DDI-445144; Signal transduction by L1.
DR Reactome; R-DDI-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-DDI-5627123; RHO GTPases activate PAKs.
DR Reactome; R-DDI-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-DDI-9013149; RAC1 GTPase cycle.
DR Reactome; R-DDI-9013404; RAC2 GTPase cycle.
DR Reactome; R-DDI-9013406; RHOQ GTPase cycle.
DR Reactome; R-DDI-9013407; RHOH GTPase cycle.
DR Reactome; R-DDI-9013420; RHOU GTPase cycle.
DR Reactome; R-DDI-9013423; RAC3 GTPase cycle.
DR Reactome; R-DDI-9013424; RHOV GTPase cycle.
DR PRO; PR:Q55GV3; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:dictyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IPI:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:dictyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0031273; P:negative regulation of pseudopodium assembly; IMP:dictyBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR Gene3D; 2.30.29.30; -; 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; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chemotaxis; Cytoplasm; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..477
FT /note="Serine/threonine-protein kinase pakC"
FT /id="PRO_0000361695"
FT DOMAIN 13..108
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 112..125
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 204..458
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 326
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 210..218
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 233
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 33
FT /note="R->C: Low basal kinase activity, loss of response to
FT chemoattractant, reduction of cell polarity and production
FT of multiple lateral pseudopodia."
FT /evidence="ECO:0000269|PubMed:15483055"
FT MUTAGEN 120
FT /note="H->L: High basal kinase activity, loss of response
FT to chemoattractant, loss of racB binding; when associated
FT with L-139."
FT /evidence="ECO:0000269|PubMed:15483055"
FT MUTAGEN 123
FT /note="H->L: High basal kinase activity, loss of response
FT to chemoattractant, loss of racB binding; when associated
FT with L-136."
FT /evidence="ECO:0000269|PubMed:15483055"
FT MUTAGEN 143
FT /note="L->F: High basal kinase activity but retains
FT response to chemoattractant."
FT /evidence="ECO:0000269|PubMed:15483055"
FT MUTAGEN 233
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15483055"
FT MUTAGEN 465
FT /note="S->A: Low basal kinase activity, loss of response to
FT chemoattractant, reduction of cell polarity and production
FT of multiple lateral pseudopodia; when associated with A-
FT 485."
FT /evidence="ECO:0000269|PubMed:15483055"
FT MUTAGEN 469
FT /note="P->A: Low basal kinase activity, loss of response to
FT chemoattractant, reduction of cell polarity and production
FT of multiple lateral pseudopodia; when associated with A-
FT 481."
FT /evidence="ECO:0000269|PubMed:15483055"
FT CONFLICT 4
FT /note="L -> LE (in Ref. 1; no nucleotide entry and 2;
FT AAF82310)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 477 AA; 54177 MW; 1BA8805095292F7C CRC64;
MISLDLSPTL WKSPDKEGEL KKQGHVVKNW KKRKFIIQND MLFYFKDKEE RPVGAVPLRM
SRCYENKSLG KPNCFELVSP RINKTFFIQA NTPDEMASWM KAVEKGSEYS TVSQPFNLKH
EVHVDFNSAT GFSGLPKEWE VILKSSNVSK QEVLDKPSEW LSVLEFQAGR TMEKSNSQNL
SALPDESNLT LSDLVTKEDP TKIYKNMTKI GEGAAGEVFV ATSSKNNKRV AIKKIEINND
NAKLLVTEIA IMKTSHHDNI VNYIDSYIVN DRELWVAMEF MGGGCLTDIL EAFDNIKMSE
IQIAYVVKET LKALQYIHSL HRIHRDIKSD NILLGSEGSV KIADFGYAAQ LTQKQQKRNT
VVGTPYWMAP ELIRGHDYGV KVDIWSLGIM MMEMAEGEPP YMDFPPLRAL FLITTKGIPP
LKETTKWSKT FQDFFSKCLD INVANRPDAT DLLKHPFMDL ACDSSEFKPL IQAARNV
