UniProtKB - Q8BTW9 (PAK4_MOUSE)
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Protein
Serine/threonine-protein kinase PAK 4
Gene
Pak4
Organism
Mus musculus (Mouse)
Status
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.
Enzyme regulationi
Inhibited by FAM212A/INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner.By similarity
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 352 | ATPPROSITE-ProRule annotation | 1 | |
| Active sitei | 442 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 329 – 337 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cadherin binding involved in cell-cell adhesion Source: MGI
- protein kinase activity Source: MGI
- protein serine/threonine kinase activity Source: UniProtKB
- Rac GTPase binding Source: GO_Central
GO - Biological processi
- actin cytoskeleton organization Source: GO_Central
- activation of protein kinase activity Source: GO_Central
- apoptotic process Source: UniProtKB-KW
- cell cycle Source: UniProtKB-KW
- cell migration Source: GO_Central
- cellular response to organic cyclic compound Source: MGI
- dendritic spine development Source: MGI
- regulation of apoptotic process Source: GO_Central
- regulation of MAPK cascade Source: GO_Central
- regulation of mitotic cell cycle Source: GO_Central
- Rho protein signal transduction Source: GO_Central
- signal transduction by protein phosphorylation Source: GO_Central
- stress-activated protein kinase signaling cascade Source: GO_Central
Keywordsi
| Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | Apoptosis, Cell cycle |
| Ligand | 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 |
| 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:1917834. Pak4. |
Subcellular locationi
- Cytoplasm By similarity
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
GO - Cellular componenti
- cell-cell adherens junction Source: MGI
- cytoplasm Source: GO_Central
- focal adhesion Source: MGI
Keywords - Cellular componenti
CytoplasmPathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000086475 | 1 – 593 | Serine/threonine-protein kinase PAK 4Add BLAST | 593 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 41 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 78 | N6-methyllysineBy similarity | 1 | |
| Modified residuei | 104 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 148 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 181 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 187 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 195 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 207 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 257 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 266 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 293 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 476 | Phosphoserine; by autocatalysisCombined sources | 1 |
Post-translational modificationi
Phosphorylated on tyrosine residues upon stimulation of FGFR2.1 Publication
Autophosphorylated on serine residues when activated by CDC42/p21.By similarity
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
| EPDi | Q8BTW9. |
| MaxQBi | Q8BTW9. |
| PaxDbi | Q8BTW9. |
| PeptideAtlasi | Q8BTW9. |
| PRIDEi | Q8BTW9. |
PTM databases
| iPTMneti | Q8BTW9. |
| PhosphoSitePlusi | Q8BTW9. |
Expressioni
Gene expression databases
| Bgeei | ENSMUSG00000030602. |
| CleanExi | MM_PAK4. |
| Genevisiblei | Q8BTW9. 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 FAM212A/INKA1 (By similarity).By similarity1 Publication
GO - Molecular functioni
- cadherin binding involved in cell-cell adhesion Source: MGI
- Rac GTPase binding Source: GO_Central
Protein-protein interaction databases
| BioGridi | 214149. 1 interactor. |
| IntActi | Q8BTW9. 1 interactor. |
| MINTi | MINT-4106515. |
| STRINGi | 10090.ENSMUSP00000032823. |
Structurei
3D structure databases
| ProteinModelPortali | Q8BTW9. |
| SMRi | Q8BTW9. |
| ModBasei | Search... |
| MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 11 – 24 | CRIBPROSITE-ProRule annotationAdd BLAST | 14 | |
| Domaini | 323 – 574 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 25 – 322 | LinkerAdd BLAST | 298 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 4 – 7 | Poly-Lys | 4 | |
| Compositional biasi | 105 – 108 | Poly-Pro | 4 | |
| Compositional biasi | 216 – 298 | Pro-richAdd BLAST | 83 | |
| Compositional biasi | 242 – 246 | Poly-Ser | 5 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated
Phylogenomic databases
| eggNOGi | KOG0578. Eukaryota. ENOG410XP4K. LUCA. |
| GeneTreei | ENSGT00860000133680. |
| HOGENOMi | HOG000234205. |
| HOVERGENi | HBG108518. |
| InParanoidi | Q8BTW9. |
| KOi | K05734. |
| OMAi | RQENGMP. |
| PhylomeDBi | Q8BTW9. |
| TreeFami | TF105352. |
Family and domain databases
| CDDi | cd01093. CRIB_PAK_like. 1 hit. |
| Gene3Di | 3.90.810.10. 1 hit. |
| InterProi | View protein in InterPro IPR000095. CRIB_dom. IPR011009. Kinase-like_dom. IPR033923. PAK_BD. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. |
| Pfami | View protein in Pfam PF00786. PBD. 1 hit. PF00069. Pkinase. 1 hit. |
| SMARTi | View protein in SMART SM00285. PBD. 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. |
Sequencei
Sequence statusi: Complete.
Q8BTW9-1 [UniParc]FASTAAdd to basket
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
Sequence cautioni
The sequence BAC98108 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 5 | K → R in AAO61496 (PubMed:12529371).Curated | 1 | |
| Sequence conflicti | 248 | P → L in AAO61496 (PubMed:12529371).Curated | 1 | |
| Sequence conflicti | 564 | T → P in BAB30889 (PubMed:16141072).Curated | 1 |
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. |
| CCDSi | CCDS21049.1. |
| RefSeqi | NP_081746.1. NM_027470.3. XP_017167785.1. XM_017312296.1. XP_017167786.1. XM_017312297.1. |
| UniGenei | Mm.21876. |
Genome annotation databases
| Ensembli | ENSMUST00000032823; ENSMUSP00000032823; ENSMUSG00000030602. ENSMUST00000108283; ENSMUSP00000103918; ENSMUSG00000030602. |
| GeneIDi | 70584. |
| KEGGi | mmu:70584. |
| UCSCi | uc009fzh.1. mouse. |
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. |
Entry informationi
| Entry namei | PAK4_MOUSE | |
| Accessioni | Q8BTW9Primary (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: | July 5, 2017 | |
| This is version 130 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families
