UniProtKB - Q61036 (PAK3_MOUSE)
Serine/threonine-protein kinase PAK 3
Pak3
Functioni
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity (PubMed:25851601).
Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (PubMed:15800193).
6 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 312 | ATPCurated | 1 | |
Active sitei | 402 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 289 – 297 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- GTPase binding Source: MGI
- MAP kinase kinase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- protein kinase activity Source: MGI
- protein serine/threonine kinase activity Source: MGI
- protein serine kinase activity Source: RHEA
- SH3 domain binding Source: UniProtKB-KW
- small GTPase binding Source: BHF-UCL
GO - Biological processi
- axonogenesis Source: UniProtKB
- cellular response to organic cyclic compound Source: MGI
- dendrite development Source: UniProtKB
- dendritic spine development Source: MGI
- dendritic spine morphogenesis Source: UniProtKB
- intracellular signal transduction Source: GO_Central
- positive regulation of dendritic spine morphogenesis Source: MGI
- positive regulation of DNA biosynthetic process Source: MGI
- positive regulation of fibroblast migration Source: MGI
- positive regulation of neuron apoptotic process Source: MGI
- protein phosphorylation Source: MGI
- regulation of actin cytoskeleton organization Source: MGI
- regulation of actin filament polymerization Source: UniProtKB
- regulation of axonogenesis Source: GO_Central
- regulation of MAPK cascade Source: GO_Central
- regulation of neuron projection development Source: MGI
Keywordsi
Molecular function | Allosteric enzyme, Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 3474 |
Reactomei | R-MMU-202433, Generation of second messenger molecules R-MMU-389359, CD28 dependent Vav1 pathway R-MMU-3928664, Ephrin signaling R-MMU-399954, Sema3A PAK dependent Axon repulsion R-MMU-5218920, VEGFR2 mediated vascular permeability R-MMU-5621575, CD209 (DC-SIGN) signaling R-MMU-5627123, RHO GTPases activate PAKs R-MMU-5687128, MAPK6/MAPK4 signaling R-MMU-9013148, CDC42 GTPase cycle R-MMU-9013149, RAC1 GTPase cycle R-MMU-9013409, RHOJ GTPase cycle R-MMU-9013420, RHOU GTPase cycle |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase PAK 3 (EC:2.7.11.1)Alternative name(s): Beta-PAK CDC42/RAC effector kinase PAK-B p21-activated kinase 3 Short name: PAK-3 |
Gene namesi | Name:Pak3 Synonyms:Pak-3, Pakb, Stk4 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1339656, Pak3 |
VEuPathDBi | HostDB:ENSMUSG00000031284 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: Reactome
Endosome
- endosome Source: MGI
Other locations
- cytoplasm Source: GO_Central
- glutamatergic synapse Source: SynGO
- postsynaptic density Source: SynGO
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 67 | R → C: Decreases interaction of PAK3 with CDC42 but increases interaction with RAC1. 1 Publication | 1 | |
Mutagenesisi | 78 | H → L: When expressed in hippocampal neurons, strongly decreases the number of dendritic spines; when associated with L-81 and R-312. 1 Publication | 1 | |
Mutagenesisi | 81 | H → L: When expressed in hippocampal neurons, strongly decreases the number of dendritic spines; when associated with L-78 and R-312. 1 Publication | 1 | |
Mutagenesisi | 312 | K → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 312 | K → R: When expressed in hippocampal neurons, decreases the number of dendritic spines. Strong decrease in the number of dendritic spines; when associated with L-78 and L-81. 1 Publication | 1 | |
Mutagenesisi | 436 | T → E: When expressed in hippocampal neurons, increases the density of both spines and dendritic protrusions. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086470 | 1 – 559 | Serine/threonine-protein kinase PAK 3Add BLAST | 559 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | PhosphoserineBy similarity | 1 | |
Modified residuei | 4 | PhosphoserineBy similarity | 1 | |
Modified residuei | 50 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 154 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 186 | PhosphoserineCombined sources | 1 | |
Modified residuei | 436 | Phosphothreonine; by autocatalysisBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q61036 |
jPOSTi | Q61036 |
MaxQBi | Q61036 |
PaxDbi | Q61036 |
PRIDEi | Q61036 |
ProteomicsDBi | 287772 [Q61036-1] 287773 [Q61036-2] |
PTM databases
iPTMneti | Q61036 |
PhosphoSitePlusi | Q61036 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000031284, Expressed in midbrain and 264 other tissues |
ExpressionAtlasi | Q61036, baseline and differential |
Genevisiblei | Q61036, MM |
Interactioni
Subunit structurei
Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK.
Interacts with the C-terminal of APP.
Interacts with ARHGEF6 and ARHGEF7 (By similarity).
Interacts with GIT1 and GIT2 (By similarity).
By similarityBinary interactionsi
Q61036
With | #Exp. | IntAct |
---|---|---|
CDC42 [P60953] from Homo sapiens. | 3 | EBI-457317,EBI-81752 |
GO - Molecular functioni
- GTPase binding Source: MGI
- SH3 domain binding Source: UniProtKB-KW
- small GTPase binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 202021, 16 interactors |
DIPi | DIP-447N |
IntActi | Q61036, 6 interactors |
MINTi | Q61036 |
STRINGi | 10090.ENSMUSP00000108485 |
Miscellaneous databases
RNActi | Q61036, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q61036 |
SMRi | Q61036 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q61036 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 70 – 83 | CRIBPROSITE-ProRule annotationAdd BLAST | 14 | |
Domaini | 283 – 534 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 70 | DisorderedSequence analysisAdd BLAST | 70 | |
Regioni | 65 – 150 | Autoregulatory regionBy similarityAdd BLAST | 86 | |
Regioni | 65 – 123 | GTPase-bindingBy similarityAdd BLAST | 59 | |
Regioni | 84 – 282 | LinkerAdd BLAST | 199 | |
Regioni | 171 – 215 | DisorderedSequence analysisAdd BLAST | 45 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 18 – 32 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 56 – 70 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 184 – 201 | Acidic residuesSequence analysisAdd BLAST | 18 |
Sequence similaritiesi
Keywords - Domaini
SH3-bindingPhylogenomic databases
eggNOGi | KOG0578, Eukaryota |
GeneTreei | ENSGT00950000182988 |
HOGENOMi | CLU_000288_26_6_1 |
InParanoidi | Q61036 |
OMAi | WYDASAT |
PhylomeDBi | Q61036 |
TreeFami | TF105351 |
Family and domain databases
CDDi | cd01093, CRIB_PAK_like, 1 hit cd06656, STKc_PAK3, 1 hit |
Gene3Di | 3.90.810.10, 1 hit |
IDEALi | IID50053 |
InterProi | View protein in InterPro IPR000095, CRIB_dom IPR036936, CRIB_dom_sf IPR011009, Kinase-like_dom_sf IPR033923, PAK_BD IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR035063, STK_PAK3 |
Pfami | View protein in Pfam PF00786, PBD, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00285, PBD, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50108, CRIB, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSDSLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS
60 70 80 90 100
IFPGGGDKTN KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM
110 120 130 140 150
CPGKLPEGIP EQWARLLQTS NITKLEQKKN PQAVLDVLKF YDSKETVNNQ
160 170 180 190 200
KYMSFTSGDK SAHGYIAAHQ SNTKTASEPP LAPPVSEEED EEEEEEEDDN
210 220 230 240 250
EPPPVIAPRP EHTKSIYTRS VVESIASPAA PNKEDIPPSA ENANSTTLYR
260 270 280 290 300
NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA
310 320 330 340 350
LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG
360 370 380 390 400
DELWVVMEYL AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH
410 420 430 440 450
RDIKSDNILL GMDGSVKLTD FGFCAQITPE QSKRSTMVGT PYWMAPEVVT
460 470 480 490 500
RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE NPLRALYLIA TNGTPELQNP
510 520 530 540 550
ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL SSLTPLIIAA
KEAIKNSSR
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA3KGC5 | A3KGC5_MOUSE | Non-specific serine/threonine prote... | Pak3 | 366 | Annotation score: | ||
A3KGC3 | A3KGC3_MOUSE | Non-specific serine/threonine prote... | Pak3 | 155 | Annotation score: | ||
A3KGC4 | A3KGC4_MOUSE | Non-specific serine/threonine prote... | Pak3 | 195 | Annotation score: | ||
A3KGC2 | A3KGC2_MOUSE | Serine/threonine-protein kinase PAK... | Pak3 | 23 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 176 | A → G in AAC52354 (PubMed:7559398).Curated | 1 | |
Sequence conflicti | 286 | F → L (PubMed:7559398).Curated | 1 | |
Sequence conflicti | 286 | F → L (PubMed:10352232).Curated | 1 | |
Sequence conflicti | 376 | E → V in AAC52354 (PubMed:7559398).Curated | 1 | |
Sequence conflicti | 508 | R → H in AAC52354 (PubMed:7559398).Curated | 1 | |
Sequence conflicti | 540 | L → M in AAC31969 (PubMed:10352232).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010243 | 93 – 107 | Missing in isoform 2. 4 PublicationsAdd BLAST | 15 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U39738 mRNA Translation: AAC52354.1 AF082297 mRNA Translation: AAC31969.1 AJ496262 mRNA Translation: CAD42790.1 AJ496263 mRNA Translation: CAD42791.1 AK031853 mRNA Translation: BAC27580.1 BC053403 mRNA Translation: AAH53403.1 |
CCDSi | CCDS30454.1 [Q61036-2] CCDS57779.1 [Q61036-1] |
PIRi | I49376 |
RefSeqi | NP_001181977.1, NM_001195048.1 [Q61036-1] NP_001181978.1, NM_001195049.1 [Q61036-2] NP_032804.2, NM_008778.3 [Q61036-2] XP_006528815.1, XM_006528752.3 [Q61036-1] XP_006528816.1, XM_006528753.3 [Q61036-2] XP_006528817.1, XM_006528754.3 [Q61036-2] XP_011246092.1, XM_011247790.2 [Q61036-2] XP_017173912.1, XM_017318423.1 |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U39738 mRNA Translation: AAC52354.1 AF082297 mRNA Translation: AAC31969.1 AJ496262 mRNA Translation: CAD42790.1 AJ496263 mRNA Translation: CAD42791.1 AK031853 mRNA Translation: BAC27580.1 BC053403 mRNA Translation: AAH53403.1 |
CCDSi | CCDS30454.1 [Q61036-2] CCDS57779.1 [Q61036-1] |
PIRi | I49376 |
RefSeqi | NP_001181977.1, NM_001195048.1 [Q61036-1] NP_001181978.1, NM_001195049.1 [Q61036-2] NP_032804.2, NM_008778.3 [Q61036-2] XP_006528815.1, XM_006528752.3 [Q61036-1] XP_006528816.1, XM_006528753.3 [Q61036-2] XP_006528817.1, XM_006528754.3 [Q61036-2] XP_011246092.1, XM_011247790.2 [Q61036-2] XP_017173912.1, XM_017318423.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1EES | NMR | - | B | 63-123 | [»] | |
AlphaFoldDBi | Q61036 | |||||
SMRi | Q61036 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 202021, 16 interactors |
DIPi | DIP-447N |
IntActi | Q61036, 6 interactors |
MINTi | Q61036 |
STRINGi | 10090.ENSMUSP00000108485 |
PTM databases
iPTMneti | Q61036 |
PhosphoSitePlusi | Q61036 |
Proteomic databases
EPDi | Q61036 |
jPOSTi | Q61036 |
MaxQBi | Q61036 |
PaxDbi | Q61036 |
PRIDEi | Q61036 |
ProteomicsDBi | 287772 [Q61036-1] 287773 [Q61036-2] |
Protocols and materials databases
Antibodypediai | 29512, 526 antibodies from 37 providers |
DNASUi | 18481 |
Genome annotation databases
Organism-specific databases
CTDi | 5063 |
MGIi | MGI:1339656, Pak3 |
VEuPathDBi | HostDB:ENSMUSG00000031284 |
Phylogenomic databases
eggNOGi | KOG0578, Eukaryota |
GeneTreei | ENSGT00950000182988 |
HOGENOMi | CLU_000288_26_6_1 |
InParanoidi | Q61036 |
OMAi | WYDASAT |
PhylomeDBi | Q61036 |
TreeFami | TF105351 |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 3474 |
Reactomei | R-MMU-202433, Generation of second messenger molecules R-MMU-389359, CD28 dependent Vav1 pathway R-MMU-3928664, Ephrin signaling R-MMU-399954, Sema3A PAK dependent Axon repulsion R-MMU-5218920, VEGFR2 mediated vascular permeability R-MMU-5621575, CD209 (DC-SIGN) signaling R-MMU-5627123, RHO GTPases activate PAKs R-MMU-5687128, MAPK6/MAPK4 signaling R-MMU-9013148, CDC42 GTPase cycle R-MMU-9013149, RAC1 GTPase cycle R-MMU-9013409, RHOJ GTPase cycle R-MMU-9013420, RHOU GTPase cycle |
Miscellaneous databases
BioGRID-ORCSi | 18481, 0 hits in 75 CRISPR screens |
ChiTaRSi | Pak3, mouse |
EvolutionaryTracei | Q61036 |
PROi | PR:Q61036 |
RNActi | Q61036, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000031284, Expressed in midbrain and 264 other tissues |
ExpressionAtlasi | Q61036, baseline and differential |
Genevisiblei | Q61036, MM |
Family and domain databases
CDDi | cd01093, CRIB_PAK_like, 1 hit cd06656, STKc_PAK3, 1 hit |
Gene3Di | 3.90.810.10, 1 hit |
IDEALi | IID50053 |
InterProi | View protein in InterPro IPR000095, CRIB_dom IPR036936, CRIB_dom_sf IPR011009, Kinase-like_dom_sf IPR033923, PAK_BD IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR035063, STK_PAK3 |
Pfami | View protein in Pfam PF00786, PBD, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00285, PBD, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50108, CRIB, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PAK3_MOUSE | |
Accessioni | Q61036Primary (citable) accession number: Q61036 Secondary accession number(s): O88645, Q8K1R5, Q8K1R6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | May 10, 2004 | |
Last modified: | May 25, 2022 | |
This is version 202 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families