KRAC_DICDI
ID KRAC_DICDI Reviewed; 444 AA.
AC P54644; Q55EY2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=RAC family serine/threonine-protein kinase homolog;
DE EC=2.7.11.1;
GN Name=pkbA; Synonyms=akt, dagA; ORFNames=DDB_G0268620;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3;
RA Moon B., Haribabu B., Rabino M., Ortiz B., Reichel G., Skehel P.,
RA Williams J., Bouzid S., Veron M., Dottin R.P.;
RT "Targeted disruption of a human rac protein kinase homolog gene encoding a
RT pleckstrin homology domain causes heterochronic development in
RT Dictyostelium.";
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
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).
RN [3]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=10205164; DOI=10.1093/emboj/18.8.2092;
RA Meili R., Ellsworth C., Lee S., Reddy T.B., Ma H., Firtel R.A.;
RT "Chemoattractant-mediated transient activation and membrane localization of
RT Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium.";
RL EMBO J. 18:2092-2105(1999).
RN [4]
RP FUNCTION.
RX PubMed=10873800; DOI=10.1016/s0960-9822(00)00536-4;
RA Meili R., Ellsworth C., Firtel R.A.;
RT "A novel Akt/PKB-related kinase is essential for morphogenesis in
RT Dictyostelium.";
RL Curr. Biol. 10:708-717(2000).
RN [5]
RP FUNCTION, AND PHOSPHORYLATION AT THR-278.
RX PubMed=18635356; DOI=10.1016/j.cub.2008.06.068;
RA Kamimura Y., Xiong Y., Iglesias P.A., Hoeller O., Bolourani P.,
RA Devreotes P.N.;
RT "PIP3-independent activation of TorC2 and PKB at the cell's leading edge
RT mediates chemotaxis.";
RL Curr. Biol. 18:1034-1043(2008).
CC -!- FUNCTION: Predominantly involved during the aggregation to control cell
CC polarity and chemotaxis. Phosphorylates talB, gefN, gefS, PI4P 5-kinase
CC and gacQ. {ECO:0000269|PubMed:10873800, ECO:0000269|PubMed:18635356}.
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 -!- DEVELOPMENTAL STAGE: Preferentially expressed during growth and
CC aggregation. {ECO:0000269|PubMed:10205164}.
CC -!- DISRUPTION PHENOTYPE: Cells exhibit aggregation-stage defects, with the
CC aggregates that form producing normal fruiting bodies.
CC {ECO:0000269|PubMed:10205164}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. RAC subfamily. {ECO:0000305}.
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DR EMBL; U15210; AAA76692.1; -; mRNA.
DR EMBL; AAFI02000004; EAL72899.1; -; Genomic_DNA.
DR RefSeq; XP_646888.1; XM_641796.1.
DR AlphaFoldDB; P54644; -.
DR SMR; P54644; -.
DR BioGRID; 1241576; 1.
DR STRING; 44689.DDB0191195; -.
DR iPTMnet; P54644; -.
DR PaxDb; P54644; -.
DR EnsemblProtists; EAL72899; EAL72899; DDB_G0268620.
DR GeneID; 8616573; -.
DR KEGG; ddi:DDB_G0268620; -.
DR dictyBase; DDB_G0268620; pkbA.
DR eggNOG; KOG0598; Eukaryota.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; P54644; -.
DR OMA; DRCECLG; -.
DR PhylomeDB; P54644; -.
DR Reactome; R-DDI-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DDI-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-DDI-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-DDI-165158; Activation of AKT2.
DR Reactome; R-DDI-165159; MTOR signalling.
DR Reactome; R-DDI-165181; Inhibition of TSC complex formation by PKB.
DR Reactome; R-DDI-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-DDI-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-DDI-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-DDI-203615; eNOS activation.
DR Reactome; R-DDI-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-DDI-389513; CTLA4 inhibitory signaling.
DR Reactome; R-DDI-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-DDI-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-DDI-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-DDI-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DDI-6804757; Regulation of TP53 Degradation.
DR Reactome; R-DDI-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-DDI-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-DDI-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-DDI-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-DDI-9031628; NGF-stimulated transcription.
DR PRO; PR:P54644; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0031252; C:cell leading edge; IDA:dictyBase.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IC:dictyBase.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IDA:dictyBase.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:dictyBase.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:dictyBase.
DR GO; GO:0019887; F:protein kinase regulator activity; TAS:dictyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:dictyBase.
DR GO; GO:0032060; P:bleb assembly; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0031154; P:culmination involved in sorocarp development; TAS:dictyBase.
DR GO; GO:0030010; P:establishment of cell polarity; IGI:dictyBase.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; TAS:dictyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0044351; P:macropinocytosis; IMP:dictyBase.
DR GO; GO:0030011; P:maintenance of cell polarity; IMP:dictyBase.
DR GO; GO:0000281; P:mitotic cytokinesis; IGI:dictyBase.
DR GO; GO:0031036; P:myosin II filament assembly; TAS:dictyBase.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:dictyBase.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IGI:dictyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0090382; P:phagosome maturation; IMP:dictyBase.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:dictyBase.
DR GO; GO:0110094; P:polyphosphate-mediated signaling; IMP:dictyBase.
DR GO; GO:1903669; P:positive regulation of chemorepellent activity; IMP:dictyBase.
DR GO; GO:1905303; P:positive regulation of macropinocytosis; IMP:dictyBase.
DR GO; GO:0006468; P:protein phosphorylation; IMP:CACAO.
DR GO; GO:0050920; P:regulation of chemotaxis; IGI:dictyBase.
DR GO; GO:1903013; P:response to differentiation-inducing factor 1; HDA:dictyBase.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:dictyBase.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
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 Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 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; Chemotaxis; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..444
FT /note="RAC family serine/threonine-protein kinase homolog"
FT /id="PRO_0000086192"
FT DOMAIN 5..100
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 120..374
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 375..444
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ACT_SITE 243
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 126..134
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 278
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18635356"
SQ SEQUENCE 444 AA; 51062 MW; 12367A1A411C5680 CRC64;
MSTAPIKHEG FLTKEGGGFK SWKKRWFILK GGDLSYYKTK GELVPLGVIH LNTSGHIKNS
DRKKRVNGFE VQTPSRTYFL CSETEEERAK WIEILINERE LLLNGGKQPK KSEKVGVADF
ELLNLVGKGS FGKVIQVRKK DTGEVYAMKV LSKKHIVEHN EVEHTLSERN ILQKINHPFL
VNLNYSFQTE DKLYFILDYV NGGELFYHLQ KDKKFTEDRV RYYGAEIVLA LEHLHLSGVI
YRDLKPENLL LTNEGHICMT DFGLCKEGLL TPTDKTGTFC GTPEYLAPEV LQGNGYGKQV
DWWSFGSLLY EMLTGLPPFY NQDVQEMYRK IMMEKLSFPH FISPDARSLL EQLLERDPEK
RLADPNLIKR HPFFRSIDWE QLFQKNIPPP FIPNVKGSAD TSQIDPVFTD EAPSLTMAGE
CALNPQQQKD FEGFTYVAES EHLR
