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Protein

Serine/threonine-protein kinase PAK 4

Gene

Pak4

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, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei352ATPPROSITE-ProRule annotation1
Active sitei442Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi329 – 337ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell cycle Source: UniProtKB-KW
  • cellular response to organic cyclic compound Source: MGI
  • dendritic spine development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 4 (EC:2.7.11.1)
Alternative name(s):
p21-activated kinase 4
Short name:
PAK-4
Gene namesi
Name:Pak4
Synonyms:Kiaa1142
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1917834. Pak4.

Subcellular locationi

  • Cytoplasm

  • Note: Seems to shuttle between cytoplasmic compartments depending on the activating effector. For example, can be found on the cell periphery after activation of growth-factor or integrin-mediated signaling pathways (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice die at embryonic day 11.5 probably due to a defect in the fetal heart. They show strong defects in neuronal development and axonal outgrowth. Spinal cord motor neurons and interneurons failed to differentiate and migrate to their proper position. Nervous system-specific conditional PAK4 deletion mice display growth retardation and die prematurely.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864751 – 593Serine/threonine-protein kinase PAK 4Add BLAST593

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei41PhosphoserineBy similarity1
Modified residuei78N6-methyllysineBy similarity1
Modified residuei104PhosphoserineBy similarity1
Modified residuei148PhosphoserineBy similarity1
Modified residuei181PhosphoserineCombined sources1
Modified residuei187PhosphothreonineBy similarity1
Modified residuei195PhosphoserineBy similarity1
Modified residuei207PhosphothreonineBy similarity1
Modified residuei257PhosphoserineBy similarity1
Modified residuei266PhosphoserineBy similarity1
Modified residuei293PhosphoserineBy similarity1
Modified residuei476Phosphoserine; by autocatalysisCombined sources1

Post-translational modificationi

Autophosphorylated on serine residues when activated by CDC42/p21.By similarity
Phosphorylated on tyrosine residues upon stimulation of FGFR2.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ8BTW9.
MaxQBiQ8BTW9.
PaxDbiQ8BTW9.
PeptideAtlasiQ8BTW9.
PRIDEiQ8BTW9.

PTM databases

iPTMnetiQ8BTW9.
PhosphoSitePlusiQ8BTW9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000030602.
CleanExiMM_PAK4.
GenevisibleiQ8BTW9. MM.

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 (By similarity). Interacts with FGFR2 and GRB2.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi214149. 1 interactor.
IntActiQ8BTW9. 1 interactor.
MINTiMINT-4106515.
STRINGi10090.ENSMUSP00000032823.

Structurei

3D structure databases

ProteinModelPortaliQ8BTW9.
SMRiQ8BTW9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 24CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini323 – 574Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 322LinkerAdd BLAST298

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 7Poly-Lys4
Compositional biasi105 – 108Poly-Pro4
Compositional biasi216 – 298Pro-richAdd BLAST83
Compositional biasi242 – 246Poly-Ser5

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234205.
HOVERGENiHBG108518.
InParanoidiQ8BTW9.
KOiK05734.
OMAiCQASHSS.
PhylomeDBiQ8BTW9.
TreeFamiTF105352.

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.
[Graphical view]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BTW9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFGKKKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP
60 70 80 90 100
KPLIDPACIT SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL
110 120 130 140 150
RRESPPPPAR AHQENGMLEE RAAPARMAPD KAGSRARATG HSEAGSGSGD
160 170 180 190 200
RRRVGPEKRP KSSRDGPGGP QEASRDKRPL SGPDVSTPQP GSLTSGTKLA
210 220 230 240 250
AGRPFNTYPR ADTDHPPRGA QGEPHTMAPN GPSATGLAAP QSSSSSRPPT
260 270 280 290 300
RARGAPSPGV LGPHASEPQL APPARALAAP AVPPAPGPPG PRSPQREPQR
310 320 330 340 350
VSHEQFRAAL QLVVDPGDPR SYLDNFIKIG EGSTGIVCIA TVRSSGKLVA
360 370 380 390 400
VKKMDLRKQQ RRELLFNEVV IMRDYRHENV VEMYNSYLVG DELWVVMEFL
410 420 430 440 450
EGGALTDIVT HTRMNEEQIA AVCLAVLQAL AVLHAQGVIH RDIKSDSILL
460 470 480 490 500
THDGRVKLSD FGFCAQVSKE VPRRKSLVGT PYWMAPELIS RLPYGPEVDI
510 520 530 540 550
WSLGVMVIEM VDGEPPYFNE PPLKAMKMIR DNLPPRLKNL HKASPSLKGF
560 570 580 590
LDRLLVRDPA QRATAAELLK HPFLTKAGPP ASIVPLMRQH RTR
Length:593
Mass (Da):64,623
Last modified:March 1, 2003 - v1
Checksum:i4AFA91DD73D4C6D5
GO

Sequence cautioni

The sequence BAC98108 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5K → R in AAO61496 (PubMed:12529371).Curated1
Sequence conflicti248P → L in AAO61496 (PubMed:12529371).Curated1
Sequence conflicti564T → P in BAB30889 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY217016 mRNA. Translation: AAO61496.1.
AK129298 mRNA. Translation: BAC98108.2. Different initiation.
AK017713 mRNA. Translation: BAB30889.1.
AK088512 mRNA. Translation: BAC40396.1.
BC048238 mRNA. Translation: AAH48238.1.
CCDSiCCDS21049.1.
RefSeqiNP_081746.1. NM_027470.3.
XP_017167785.1. XM_017312296.1.
XP_017167786.1. XM_017312297.1.
UniGeneiMm.21876.

Genome annotation databases

EnsembliENSMUST00000032823; ENSMUSP00000032823; ENSMUSG00000030602.
ENSMUST00000108283; ENSMUSP00000103918; ENSMUSG00000030602.
GeneIDi70584.
KEGGimmu:70584.
UCSCiuc009fzh.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY217016 mRNA. Translation: AAO61496.1.
AK129298 mRNA. Translation: BAC98108.2. Different initiation.
AK017713 mRNA. Translation: BAB30889.1.
AK088512 mRNA. Translation: BAC40396.1.
BC048238 mRNA. Translation: AAH48238.1.
CCDSiCCDS21049.1.
RefSeqiNP_081746.1. NM_027470.3.
XP_017167785.1. XM_017312296.1.
XP_017167786.1. XM_017312297.1.
UniGeneiMm.21876.

3D structure databases

ProteinModelPortaliQ8BTW9.
SMRiQ8BTW9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi214149. 1 interactor.
IntActiQ8BTW9. 1 interactor.
MINTiMINT-4106515.
STRINGi10090.ENSMUSP00000032823.

PTM databases

iPTMnetiQ8BTW9.
PhosphoSitePlusiQ8BTW9.

Proteomic databases

EPDiQ8BTW9.
MaxQBiQ8BTW9.
PaxDbiQ8BTW9.
PeptideAtlasiQ8BTW9.
PRIDEiQ8BTW9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032823; ENSMUSP00000032823; ENSMUSG00000030602.
ENSMUST00000108283; ENSMUSP00000103918; ENSMUSG00000030602.
GeneIDi70584.
KEGGimmu:70584.
UCSCiuc009fzh.1. mouse.

Organism-specific databases

CTDi10298.
MGIiMGI:1917834. Pak4.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234205.
HOVERGENiHBG108518.
InParanoidiQ8BTW9.
KOiK05734.
OMAiCQASHSS.
PhylomeDBiQ8BTW9.
TreeFamiTF105352.

Miscellaneous databases

ChiTaRSiPak4. mouse.
PROiQ8BTW9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030602.
CleanExiMM_PAK4.
GenevisibleiQ8BTW9. 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.
[Graphical view]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAK4_MOUSE
AccessioniPrimary (citable) accession number: Q8BTW9
Secondary accession number(s): Q6ZPX0, Q80Z97, Q9CS71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.