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Protein

Serine/threonine-protein kinase PAK 4

Gene

Pak4

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, 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.

Activity regulationi

Inhibited by INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner.By similarity

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

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB
  • Rac GTPase binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1917834 Pak4

Subcellular locationi

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 (PubMed:12529371).By similarity1 Publication
Polyubiquitinated, leading to its proteasomal degradation.By similarity

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8BTW9
MaxQBiQ8BTW9
PaxDbiQ8BTW9
PeptideAtlasiQ8BTW9
PRIDEiQ8BTW9

PTM databases

iPTMnetiQ8BTW9
PhosphoSitePlusiQ8BTW9

Expressioni

Gene expression databases

BgeeiENSMUSG00000030602 Expressed in 255 organ(s), highest expression level in intestine
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 (PubMed:12529371). Interacts with INKA1. Interacts with SH3RF2 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi214149, 1 interactor
IntActiQ8BTW9, 1 interactor
MINTiQ8BTW9
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

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00930000150829
HOGENOMiHOG000234205
HOVERGENiHBG108518
InParanoidiQ8BTW9
KOiK05734
OMAiARQENGM
PhylomeDBiQ8BTW9
TreeFamiTF105352

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 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

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

Similar proteinsi

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
MINTiQ8BTW9
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
GeneTreeiENSGT00930000150829
HOGENOMiHOG000234205
HOVERGENiHBG108518
InParanoidiQ8BTW9
KOiK05734
OMAiARQENGM
PhylomeDBiQ8BTW9
TreeFamiTF105352

Miscellaneous databases

ChiTaRSiPak4 mouse
PROiPR:Q8BTW9
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030602 Expressed in 255 organ(s), highest expression level in intestine
CleanExiMM_PAK4
GenevisibleiQ8BTW9 MM

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 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
ProtoNetiSearch...

Entry informationi

Entry nameiPAK4_MOUSE
AccessioniPrimary (citable) accession number: Q8BTW9
Secondary accession number(s): Q6ZPX0, Q80Z97, Q9CS71
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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