PAKA_DICDI
ID PAKA_DICDI Reviewed; 1197 AA.
AC Q55D99; Q23866; Q9XYY3;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Serine/threonine-protein kinase pakA;
DE Short=dPAKa;
DE EC=2.7.11.1;
DE AltName: Full=dpak1;
GN Name=pakA; ORFNames=DDB_G0269166;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX3-1;
RX PubMed=10545500; DOI=10.1083/jcb.147.3.559;
RA Chung C.Y., Firtel R.A.;
RT "PAKa, a putative PAK family member, is required for cytokinesis and the
RT regulation of the cytoskeleton in Dictyostelium discoideum cells during
RT chemotaxis.";
RL J. Cell Biol. 147:559-576(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3;
RA Mueller-Taubenberger A.;
RL Submitted (OCT-1999) 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).
RN [4]
RP FUNCTION, MUTAGENESIS OF THR-585, AND PHOSPHORYLATION AT THR-585.
RX PubMed=11389841; DOI=10.1016/s1097-2765(01)00247-7;
RA Chung C.Y., Potikyan G., Firtel R.A.;
RT "Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through
RT the regulation of PAKa.";
RL Mol. Cell 7:937-947(2001).
CC -!- FUNCTION: Regulator of the myosin II component of the cytoskeleton:
CC required for regulation of cytokinesis. Functions during chemotaxis,
CC required for maintaining the direction of cell movement, suppressing
CC lateral pseudopod extension, and proper retraction of the posterior of
CC chemotaxing cells. {ECO:0000269|PubMed:10545500,
CC ECO:0000269|PubMed:11389841}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10545500}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10545500}. Note=Cytosolic
CC in unstimulated cells, localizes to the cytoskeleton in response to
CC chemoattractant stimulation.
CC -!- TISSUE SPECIFICITY: Colocalizes with myosin II to the cleavage furrow
CC of cells undergoing cytokinesis and the posterior cortex of polarized
CC cells. {ECO:0000269|PubMed:10545500}.
CC -!- PTM: Phosphorylation on Thr-585 results in cAMP-mediated activation and
CC localization to the cytoskeleton. {ECO:0000269|PubMed:11389841}.
CC -!- DISRUPTION PHENOTYPE: cells exhibit a defect in completing cytokinesis
CC when grown in suspension, suggesting difficulties in regulating
CC cytoskeletal organization required for cytokinesis, although
CC karyokinesis is normal. {ECO:0000269|PubMed:10545500}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AF131221; AAD28470.1; -; mRNA.
DR EMBL; U51923; AAA93038.2; -; mRNA.
DR EMBL; AAFI02000005; EAL71933.1; -; Genomic_DNA.
DR RefSeq; XP_646232.1; XM_641140.1.
DR AlphaFoldDB; Q55D99; -.
DR SMR; Q55D99; -.
DR BioGRID; 1242191; 1.
DR STRING; 44689.DDB0191313; -.
DR iPTMnet; Q55D99; -.
DR PaxDb; Q55D99; -.
DR EnsemblProtists; EAL71933; EAL71933; DDB_G0269166.
DR GeneID; 8617188; -.
DR KEGG; ddi:DDB_G0269166; -.
DR dictyBase; DDB_G0269166; pakA.
DR eggNOG; KOG0578; Eukaryota.
DR HOGENOM; CLU_271206_0_0_1; -.
DR InParanoid; Q55D99; -.
DR OMA; SWADRRE; -.
DR Reactome; R-DDI-389359; CD28 dependent Vav1 pathway.
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:Q55D99; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0031254; C:cell trailing edge; IDA:dictyBase.
DR GO; GO:0032154; C:cleavage furrow; IDA:dictyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0097204; C:phagocytic cup base; IDA:dictyBase.
DR GO; GO:0001931; C:uropod; 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:0045159; F:myosin II binding; IMP:UniProtKB.
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:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0048870; P:cell motility; IMP:dictyBase.
DR GO; GO:0006935; P:chemotaxis; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:UniProtKB.
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:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0031036; P:myosin II filament assembly; IMP:dictyBase.
DR GO; GO:0006909; P:phagocytosis; IMP:dictyBase.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
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:0031156; P:regulation of sorocarp development; IMP:dictyBase.
DR GO; GO:1903013; P:response to differentiation-inducing factor 1; HDA:dictyBase.
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 Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chemotaxis; Cytoplasm; Cytoskeleton; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1197
FT /note="Serine/threonine-protein kinase pakA"
FT /id="PRO_0000327474"
FT DOMAIN 817..830
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 911..1164
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 562..819
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 51..69
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 70..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..383
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..543
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 588..616
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 634..726
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 740..755
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 756..792
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1032
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 917..925
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 940
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 585
FT /note="Phosphothreonine; by PKB"
FT /evidence="ECO:0000269|PubMed:11389841"
FT MUTAGEN 585
FT /note="T->A: Loss of phosphorylation in response to cAMP."
FT /evidence="ECO:0000269|PubMed:11389841"
FT MUTAGEN 585
FT /note="T->D: Constitutively active."
FT /evidence="ECO:0000269|PubMed:11389841"
FT CONFLICT 30
FT /note="K -> R (in Ref. 1; AAD28470 and 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 48..53
FT /note="Missing (in Ref. 1; AAD28470)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="Q -> H (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="E -> D (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 379..380
FT /note="NK -> F (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="N -> Y (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 466..467
FT /note="QR -> LL (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="H -> L (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 1081
FT /note="G -> S (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 1085
FT /note="D -> N (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
FT CONFLICT 1113
FT /note="L -> H (in Ref. 2; AAA93038)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1197 AA; 134650 MW; 3B76B9D3F073F51E CRC64;
MEEKPKSTTP PPSVSSLRQK FEQFLDKTDK GFNATRNNYR GPVSSSTGII NDKEKKSHSY
FKVREEGSNK RPSSFSASNP ITPSSPQSTH SSPIYRGVGY HQYSSVNSGN SYSGSGNNIN
NIINNSNNSN SNNLYGNNSN NQSSGSLGNF LIDKLEYSAA TVTASDLKRE RQQLFRNKEE
FTMESSSYGG STIGDDDLDS LNGSSSQQFN HRNSSWADRR ERFIKKVMNG QFNEVQMRDE
LNRLRDIEAD KIRAEERRTP SMNMDEFKAI EIERLRKKIY QEELVIFRQE EIEKIQREER
IKIEKEYDDK SIISSQERQH IVQQIINQKE DEKGSSPPFP IPLVVNNNNN ENNENDNNNN
NNNNNNNNNN NNNNNNNNNK NIDLTSFNNN ININSNNNEI KNNVIVDSDD EEELERLEQL
RRQREIERLR EEEEENEDRV ERELASRRRQ EEDRIKREEE EEEEEQRNYL RRLKELERIK
QIEEEEEEER ERQSQLQSSQ QQQKSSSTQR SSNTVTSTSS SSTGGDSNPS TSQKPTNLLN
LMGSNNNISN INTNILSHSI VNSSGGLPPP PPTASHVDNR SRSHTLAGES HSSENTPLVS
SIDNNGVNNK MSRSHSGGAL SGLALPTAPP LPNQPNVNNS NNNNNNNNIN NNHNHSHNHS
NNLHQSALKN SSSMSTPSIS PSQAGNSATS TVPSSPISAS TSMSSPTLVV SPRKDELTTS
TGSTRKGSIS EREDKKKVSS SSTSSSSSSN GGLSSSGKDH KKDHSSEEKE KEKKSFFNKL
FSKEKKDHHS SSKSPSSGSS GGGEVDEKKK KKLSPRVGTP FNVKHDVHVN FNADTGFEGL
PKEWEVLIKS NFQEPEVMQH PEEVLDVVKF HAQYQGLASA PAMHAPSIPL TDEPPVTLND
LISLDDPKKI YYNINKIGEG GAGEVFEAIN SRTNQTIAIK KMKLKAQNLK TVINEIGMMK
NSNHENIVQY IDSYIVADEL WVAMEFMSGG CLTEVLDQYR DIQLNESQIA FVCQEVLRGL
EYIHKFNRIH RDIKSDNILI GANGEIKLAD FGYAAQLTQI RQERNSVVGT PYWMAPELIR
GNNYDFKVDV WSLGIMTREM AEGEPPYLEF PPLRALFLLT TQGLPPIRDA HKWSKEFNDF
LALCLEKDTE KRASSSSLLH HPFLKRACSG PEFYKAVDAA RIEKENQLQN FANLTAI
