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UniProtKB - Q61036 (PAK3_MOUSE)

Protein

Serine/threonine-protein kinase PAK 3

Gene

Pak3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (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.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Activity 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

  • 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
  • Rac GTPase binding Source: GO_Central
  • Rho GTPase binding Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionAllosteric enzyme, Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1339656 Pak3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 237 organ(s), highest expression level in ventromedial nucleus of hypothalamus
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 Homo sapiens.

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi202021, 5 interactors
DIPiDIP-447N
IntActiQ61036, 7 interactors
MINTiQ61036
STRINGi10090.ENSMUSP00000033640

Structurei

Secondary structure

1559
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00930000150829
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiQ61036
KOiK05733
OMAiNENQMAY
OrthoDBiEOG091G04H8
TreeFamiTF105351

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
cd06656 STKc_PAK3, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR035065 PAK2/3
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR035063 STK_PAK3
PANTHERiPTHR24361:SF250 PTHR24361:SF250, 1 hit
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView 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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A3KGC5A3KGC5_MOUSE
Serine/threonine-protein kinase PAK...
Pak3
366Annotation score:
A3KGC3A3KGC3_MOUSE
Serine/threonine-protein kinase PAK...
Pak3
155Annotation score:
A3KGC4A3KGC4_MOUSE
Serine/threonine-protein kinase PAK...
Pak3
195Annotation score:
A3KGC2A3KGC2_MOUSE
Serine/threonine-protein kinase PAK...
Pak3
23Annotation score:

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

Similar 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
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, 5 interactors
DIPiDIP-447N
IntActiQ61036, 7 interactors
MINTiQ61036
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
GeneTreeiENSGT00930000150829
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiQ61036
KOiK05733
OMAiNENQMAY
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
PROiPR:Q61036
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031284 Expressed in 237 organ(s), highest expression level in ventromedial nucleus of hypothalamus
CleanExiMM_PAK3
MM_STK4
ExpressionAtlasiQ61036 baseline and differential
GenevisibleiQ61036 MM

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
cd06656 STKc_PAK3, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR035065 PAK2/3
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR035063 STK_PAK3
PANTHERiPTHR24361:SF250 PTHR24361:SF250, 1 hit
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView 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
ProtoNetiSearch...

Entry informationi

Entry nameiPAK3_MOUSE
AccessioniPrimary (citable) accession number: Q61036
Secondary accession number(s): O88645, Q8K1R5, Q8K1R6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 10, 2004
Last modified: November 7, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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