PAK3_PONPY
ID PAK3_PONPY Reviewed; 559 AA.
AC Q7YQL3;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Serine/threonine-protein kinase PAK 3;
DE EC=2.7.11.1;
DE AltName: Full=Beta-PAK;
DE AltName: Full=p21-activated kinase 3;
DE Short=PAK-3;
GN Name=PAK3;
OS Pongo pygmaeus (Bornean orangutan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9600;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12777533; DOI=10.1093/molbev/msg134;
RA Kitano T., Schwarz C., Nickel B., Paeaebo S.;
RT "Gene diversity patterns at 10 X-chromosomal loci in humans and
RT chimpanzees.";
RL Mol. Biol. Evol. 20:1281-1289(2003).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell migration, or cell cycle regulation. Plays a role in
CC dendrite spine morphogenesis as well as synapse formation and
CC plasticity. Acts as downstream effector of the small GTPases CDC42 and
CC RAC1. Activation by the binding of active CDC42 and RAC1 results in a
CC conformational change and a subsequent autophosphorylation on several
CC serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and
CC activates the downstream target MAPKAPK5, a regulator of F-actin
CC polymerization and cell migration. Additionally, phosphorylates
CC TNNI3/troponin I to modulate calcium sensitivity and relaxation
CC kinetics of thin myofilaments. May also be involved in early neuronal
CC development (By similarity). In hippocampal neurons, necessary for the
CC formation of dendritic spines and excitatory synapses; this function is
CC dependent on kinase activity and may be exerted by the regulation of
CC actomyosin contractility through the phosphorylation of myosin II
CC regulatory light chain (MLC) (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q61036}.
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; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by binding small G proteins. Binding of
CC GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers
CC from the autoinhibited dimer, enables phosphorylation of Thr-436 and
CC allows the kinase domain to adopt an active structure (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21
CC and RAC1. Shows highly specific binding to the SH3 domains of
CC phospholipase C-gamma and of adapter protein NCK. Interacts with the C-
CC terminal of APP. Interacts with ARHGEF6 and ARHGEF7 (By similarity).
CC Interacts with GIT1 and GIT2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O75914}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Autophosphorylated when activated by CDC42/p21. {ECO:0000250}.
CC -!- PTM: Neddylated. {ECO:0000250}.
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; AB102661; BAC81130.1; -; mRNA.
DR AlphaFoldDB; Q7YQL3; -.
DR SMR; Q7YQL3; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion 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; IEA:UniProtKB-KW.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0030833; P:regulation of actin filament polymerization; ISS:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR CDD; cd06656; STKc_PAK3; 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; IPR035063; STK_PAK3.
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; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Developmental protein; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Serine/threonine-protein kinase; SH3-binding; Transferase; Ubl conjugation.
FT CHAIN 1..559
FT /note="Serine/threonine-protein kinase PAK 3"
FT /id="PRO_0000086472"
FT DOMAIN 70..83
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 283..534
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..150
FT /note="Autoregulatory region"
FT /evidence="ECO:0000250"
FT REGION 65..123
FT /note="GTPase-binding"
FT /evidence="ECO:0000250"
FT REGION 84..282
FT /note="Linker"
FT REGION 164..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..72
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..201
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 402
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 289..297
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 50
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 154
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61036"
FT MOD_RES 436
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
SQ SEQUENCE 559 AA; 62310 MW; BC39AEC6F0A5478B CRC64;
MSDGLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN
KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM CPGKLPEGIP EQWARLLQTS
NITKLEQKKN PQAVLDVLKF YDSKETVNNQ KYMSFTSGDK SAHGYIAAHP SSTKTASEPP
LAPPVSEEED EEEEEEEDEN EPPPVIAPRP EHTKSIYTRS VVESIASPAV PNKEVTPPSA
ENANSSTLYR NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA
LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG DELWVVMEYL
AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH RDIKSDNILL GMDGSVKLTD
FGFCAQITPE QSKRSTMVGT PYWMAPEVVT RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE
NPLRALYLIA TNGTPELQNP ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL
SSLTPLIIAA KEAIKNSSR
