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Protein

Serine/threonine-protein kinase PAK 3

Gene

Pak3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. 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.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei312ATPCurated1
Active sitei402Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi289 – 297ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: GO_Central
  • axonogenesis Source: UniProtKB
  • cellular response to organic cyclic compound Source: MGI
  • dendrite development Source: UniProtKB
  • dendritic spine development Source: MGI
  • positive regulation of dendritic spine morphogenesis Source: Ensembl
  • positive regulation of DNA biosynthetic process Source: Ensembl
  • positive regulation of fibroblast migration Source: Ensembl
  • positive regulation of neuron apoptotic process Source: Ensembl
  • regulation of actin filament polymerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.12. 3474.
2.7.11.1. 3474.
ReactomeiR-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.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1339656. Pak3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice show significant abnormalities in synaptic plasticity as well as deficiencies in learning and memory. Pak1 and Pak3 double knockout mice display reduced brains characterized by simplified neuronal dendrites/axons and reduced synapse density.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67R → C: Decreases interaction of PAK3 with CDC42 but increases interaction with RAC1. 1 Publication1
Mutagenesisi312K → A: Loss of kinase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864701 – 559Serine/threonine-protein kinase PAK 3Add BLAST559

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphoserineBy similarity1
Modified residuei4PhosphoserineBy similarity1
Modified residuei50Phosphoserine; by autocatalysisBy similarity1
Modified residuei154Phosphoserine; by autocatalysisBy similarity1
Modified residuei186PhosphoserineCombined sources1
Modified residuei436Phosphothreonine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated when activated by CDC42/p21.
Neddylated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ61036.
PRIDEiQ61036.

PTM databases

iPTMnetiQ61036.
PhosphoSitePlusiQ61036.

Expressioni

Gene expression databases

BgeeiENSMUSG00000031284.
CleanExiMM_PAK3.
MM_STK4.
ExpressionAtlasiQ61036. baseline and differential.
GenevisibleiQ61036. 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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC42P609533EBI-457317,EBI-81752From a different organism.

GO - Molecular functioni

  • Rho GTPase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi202021. 3 interactors.
DIPiDIP-447N.
IntActiQ61036. 5 interactors.
MINTiMINT-151864.
STRINGi10090.ENSMUSP00000033640.

Structurei

Secondary structure

1559
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi115 – 118Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EESNMR-B63-123[»]
ProteinModelPortaliQ61036.
SMRiQ61036.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61036.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini70 – 83CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini283 – 534Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 150Autoregulatory regionBy similarityAdd BLAST86
Regioni65 – 123GTPase-bindingBy similarityAdd BLAST59
Regioni84 – 282LinkerAdd BLAST199

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi187 – 197Poly-GluAdd BLAST11

Sequence similaritiesi

Contains 1 CRIB domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ61036.
KOiK05733.
OMAiXCLQALD.
OrthoDBiEOG091G04H8.
TreeFamiTF105351.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61036-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:559
Mass (Da):62,398
Last modified:May 10, 2004 - v2
Checksum:i9AD07B0328F0B08C
GO
Isoform 2 (identifier: Q61036-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     93-107: Missing.

Show »
Length:544
Mass (Da):60,781
Checksum:i72E323575DC18E0F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti176A → G in AAC52354 (PubMed:7559398).Curated1
Sequence conflicti286F → L (PubMed:7559398).Curated1
Sequence conflicti286F → L (PubMed:10352232).Curated1
Sequence conflicti376E → V in AAC52354 (PubMed:7559398).Curated1
Sequence conflicti508R → H in AAC52354 (PubMed:7559398).Curated1
Sequence conflicti540L → M in AAC31969 (PubMed:10352232).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01024393 – 107Missing in isoform 2. 4 PublicationsAdd BLAST15

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.
CCDSiCCDS30454.1. [Q61036-2]
CCDS57779.1. [Q61036-1]
PIRiI49376.
RefSeqiNP_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. [Q61036-1]
UniGeneiMm.40035.

Genome annotation databases

EnsembliENSMUST00000033640; ENSMUSP00000033640; ENSMUSG00000031284. [Q61036-1]
ENSMUST00000112863; ENSMUSP00000108484; ENSMUSG00000031284. [Q61036-1]
ENSMUST00000112864; ENSMUSP00000108485; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000112865; ENSMUSP00000108486; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000112868; ENSMUSP00000108489; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000172330; ENSMUSP00000126562; ENSMUSG00000031284. [Q61036-2]
GeneIDi18481.
KEGGimmu:18481.
UCSCiuc009umg.2. mouse. [Q61036-1]
uc009umh.2. mouse. [Q61036-2]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS30454.1. [Q61036-2]
CCDS57779.1. [Q61036-1]
PIRiI49376.
RefSeqiNP_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. [Q61036-1]
UniGeneiMm.40035.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EESNMR-B63-123[»]
ProteinModelPortaliQ61036.
SMRiQ61036.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202021. 3 interactors.
DIPiDIP-447N.
IntActiQ61036. 5 interactors.
MINTiMINT-151864.
STRINGi10090.ENSMUSP00000033640.

PTM databases

iPTMnetiQ61036.
PhosphoSitePlusiQ61036.

Proteomic databases

PaxDbiQ61036.
PRIDEiQ61036.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033640; ENSMUSP00000033640; ENSMUSG00000031284. [Q61036-1]
ENSMUST00000112863; ENSMUSP00000108484; ENSMUSG00000031284. [Q61036-1]
ENSMUST00000112864; ENSMUSP00000108485; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000112865; ENSMUSP00000108486; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000112868; ENSMUSP00000108489; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000172330; ENSMUSP00000126562; ENSMUSG00000031284. [Q61036-2]
GeneIDi18481.
KEGGimmu:18481.
UCSCiuc009umg.2. mouse. [Q61036-1]
uc009umh.2. mouse. [Q61036-2]

Organism-specific databases

CTDi5063.
MGIiMGI:1339656. Pak3.

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ61036.
KOiK05733.
OMAiXCLQALD.
OrthoDBiEOG091G04H8.
TreeFamiTF105351.

Enzyme and pathway databases

BRENDAi2.7.1.12. 3474.
2.7.11.1. 3474.
ReactomeiR-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.

Miscellaneous databases

EvolutionaryTraceiQ61036.
PROiQ61036.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031284.
CleanExiMM_PAK3.
MM_STK4.
ExpressionAtlasiQ61036. baseline and differential.
GenevisibleiQ61036. MM.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAK3_MOUSE
AccessioniPrimary (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: November 30, 2016
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.