PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically ... See more...

Aliases for PAK4 Gene

Aliases for PAK4 Gene

  • P21 (RAC1) Activated Kinase 4 2 3 5
  • P21 Protein (Cdc42/Rac)-Activated Kinase 4 2 3
  • Serine/Threonine-Protein Kinase PAK 4 3 4
  • P21(CDKN1A)-Activated Kinase 4 2 3
  • EC 2.7.11.1 4 51
  • Protein Kinase Related To S. Cerevisiae STE20, Effector For Cdc42Hs 3
  • P21-Activated Kinase 4 4
  • EC 2.7.11 51
  • KIAA1142 4
  • PAK-4 4
  • PAK4 5

External Ids for PAK4 Gene

Previous GeneCards Identifiers for PAK4 Gene

  • GC19P040228
  • GC19P040007
  • GC19P044292
  • GC19P044308
  • GC19P044274
  • GC19P039616
  • GC19P036064

Summaries for PAK4 Gene

Entrez Gene Summary for PAK4 Gene

  • PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically with the GTP-bound form of Cdc42Hs and weakly activates the JNK family of MAP kinases. PAK4 is a mediator of filopodia formation and may play a role in the reorganization of the actin cytoskeleton. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for PAK4 Gene

PAK4 (P21 (RAC1) Activated Kinase 4) is a Protein Coding gene. Diseases associated with PAK4 include Polycystic Kidney Disease 3 With Or Without Polycystic Liver Disease. Among its related pathways are Integrin Pathway and Guidance Cues and Growth Cone Motility. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is PAK5.

UniProtKB/Swiss-Prot Summary for PAK4 Gene

  • 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.

Gene Wiki entry for PAK4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PAK4 Gene

Genomics for PAK4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PAK4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PAK4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PAK4

Top Transcription factor binding sites by QIAGEN in the PAK4 gene promoter:
  • AREB6
  • CBF(2)
  • E47
  • Hand1
  • NF-kappaB
  • NF-kappaB1
  • NF-kappaB2
  • NF-Y

Genomic Locations for PAK4 Gene

Genomic Locations for PAK4 Gene
chr19:39,125,770-39,182,816
(GRCh38/hg38)
Size:
57,047 bases
Orientation:
Plus strand
chr19:39,616,410-39,673,456
(GRCh37/hg19)
Size:
57,047 bases
Orientation:
Plus strand

Genomic View for PAK4 Gene

Genes around PAK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PAK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PAK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PAK4 Gene

Proteins for PAK4 Gene

  • Protein details for PAK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O96013-PAK4_HUMAN
    Recommended name:
    Serine/threonine-protein kinase PAK 4
    Protein Accession:
    O96013
    Secondary Accessions:
    • B4DGG6
    • Q8N4E1
    • Q8NCH5
    • Q8NDE3
    • Q9BU33
    • Q9ULS8

    Protein attributes for PAK4 Gene

    Size:
    591 amino acids
    Molecular mass:
    64072 Da
    Quaternary structure:
    • Interacts with FGFR2 and GRB2 (By similarity). Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 (PubMed:15827085). Interacts with INKA1 (PubMed:26607847). Interacts with SH3RF2 (PubMed:24130170).
    SequenceCaution:
    • Sequence=BAA86456.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC11166.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PAK4 Gene

    Alternative splice isoforms for PAK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PAK4 Gene

Selected DME Specific Peptides for PAK4 Gene

O96013:
  • GPEVDIWS
  • LEGGALTDIVTH
  • EVDIWSLG
  • PSNFEHRVHTGFD
  • DFGFCAQ
  • MDLRKQQRRELLFNEVVIMRDY
  • HEQFRAALQ
  • KIGEGSTG
  • GTPYWMAPE
  • QGVIHRDIKSDSILL
  • SYLVGDELWVVME

Post-translational modifications for PAK4 Gene

  • Autophosphorylated on serine residues when activated by CDC42/p21 (Ref.31). Phosphorylated on tyrosine residues upon stimulation of FGFR2 (By similarity).
  • Polyubiquitinated, leading to its proteasomal degradation.
  • Ubiquitination at Lys31
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for PAK4

Domains & Families for PAK4 Gene

Gene Families for PAK4 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for PAK4 Gene

InterPro:
Blocks:
  • PAK-box/P21-Rho-binding
ProtoNet:

Suggested Antigen Peptide Sequences for PAK4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ55049, highly similar to Serine/threonine-protein kinase PAK 4 (EC 2.7.11.1) (B4DE88_HUMAN)
  • cDNA FLJ61413, highly similar to Serine/threonine-protein kinase PAK 4 (EC 2.7.11.1) (B4DUG0_HUMAN)
  • p21-activated kinase 4 (PAK4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O96013

UniProtKB/Swiss-Prot:

PAK4_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
genes like me logo Genes that share domains with PAK4: view

Function for PAK4 Gene

Molecular function for PAK4 Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner (PubMed:26607847).

Enzyme Numbers (IUBMB) for PAK4 Gene

Phenotypes From GWAS Catalog for PAK4 Gene

Gene Ontology (GO) - Molecular Function for PAK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity NAS 9822598
GO:0004674 protein serine/threonine kinase activity IMP 21788589
GO:0005515 protein binding IPI 15161933
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with PAK4: view
genes like me logo Genes that share phenotypes with PAK4: view

Animal Models for PAK4 Gene

MGI Knock Outs for PAK4:
  • Pak4 Pak4<tm1Amin>
  • Pak4 Pak4<tm2.2Amin>

Animal Model Products

  • Taconic Biosciences Mouse Models for PAK4

CRISPR Products

miRNA for PAK4 Gene

miRTarBase miRNAs that target PAK4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PAK4

Clone Products

  • Addgene plasmids for PAK4

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PAK4 Gene

Localization for PAK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PAK4 Gene

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. {ECO:0000269 PubMed:12356872}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PAK4 gene
Compartment Confidence
golgi apparatus 4
nucleus 3
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PAK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005794 Golgi apparatus TAS 9822598
GO:0005912 adherens junction HDA 25468996
GO:0005925 focal adhesion HDA 21423176
genes like me logo Genes that share ontologies with PAK4: view

Pathways & Interactions for PAK4 Gene

PathCards logo

SuperPathways for PAK4 Gene

SuperPathway Contained pathways
1 Integrin Pathway
.67
.67
.56
.38
2 ErbB signaling pathway
3 Focal Adhesion
4 fMLP Pathway
.44
.39
.31
5 ERK Signaling
.61
.61
.58
genes like me logo Genes that share pathways with PAK4: view

Pathways by source for PAK4 Gene

2 GeneGo (Thomson Reuters) pathways for PAK4 Gene
  • Cytoskeleton remodeling CDC42 in cellular processes
  • Cytoskeleton remodeling_Role of PDGFs in cell migration
32 Qiagen pathways for PAK4 Gene
  • Actin Nucleation and Branching
  • Actin-Based Motility by Rho Family GTPases
  • Agrin Interactions at Neuromuscular Junction
  • Angiopoietin-TIE2 Signaling
  • CCR3 Pathway in Eosinophils
1 Cell Signaling Technology pathway for PAK4 Gene

SIGNOR curated interactions for PAK4 Gene

Activates:
Is activated by:
Other effect:

Gene Ontology (GO) - Biological Process for PAK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth TAS 20070256
GO:0006468 protein phosphorylation IEA --
GO:0006915 apoptotic process TAS 20070256
GO:0007010 cytoskeleton organization TAS 20070256
GO:0007049 cell cycle IEA --
genes like me logo Genes that share ontologies with PAK4: view

Drugs & Compounds for PAK4 Gene

(25) Drugs for PAK4 Gene - From: DrugBank, ClinicalTrials, ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nicotinamide Approved, Investigational Pharma 427,427
Niacin Approved, Investigational Nutra Agonist, Unknown, Full agonist 432,432
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
nivolumab Approved Pharma Therapeutic Antibodies, Immunotherapies 1165
Folic acid Approved, Vet_approved Nutra 4765

(1) Additional Compounds for PAK4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0

(2) ApexBio Compounds for PAK4 Gene

Compound Action Cas Number
KPT-9274 Orally acitve allosteric inhibitor of PAK4 1643913-93-2
PF-3758309 PAK4 inhibitor 898044-15-0
genes like me logo Genes that share compounds with PAK4: view

Drug Products

Transcripts for PAK4 Gene

mRNA/cDNA for PAK4 Gene

6 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PAK4

Clone Products

  • Addgene plasmids for PAK4

Alternative Splicing Database (ASD) splice patterns (SP) for PAK4 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f · 1g ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14a · 14b
SP1: -
SP2: - -
SP3: - -
SP4: - - -
SP5: - - -
SP6: - - - -
SP7: - - - - - -
SP8: - - - - - - -
SP9: - - - -
SP10: - - - - - - - - -
SP11: - - - - -
SP12: - - - - - - - -
SP13:
SP14:

Relevant External Links for PAK4 Gene

GeneLoc Exon Structure for
PAK4

Expression for PAK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PAK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PAK4 Gene

This gene is overexpressed in Breast (52.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PAK4 Gene



Protein tissue co-expression partners for PAK4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PAK4

SOURCE GeneReport for Unigene cluster for PAK4 Gene:

Hs.20447

mRNA Expression by UniProt/SwissProt for PAK4 Gene:

O96013-PAK4_HUMAN
Tissue specificity: Highest expression in prostate, testis and colon.

Evidence on tissue expression from TISSUES for PAK4 Gene

  • Nervous system(4.8)
  • Pancreas(4.7)
  • Liver(4.5)
  • Eye(4.4)
  • Skin(2.9)
  • Kidney(2.5)
  • Lung(2.5)
  • Heart(2.4)
  • Intestine(2.2)
  • Muscle(2.2)
  • Blood(2.1)
  • Adrenal gland(2.1)
  • Stomach(2)
genes like me logo Genes that share expression patterns with PAK4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for PAK4 Gene

Orthologs for PAK4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PAK4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PAK4 31
  • 95 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia PAK4 30 31
  • 91.4 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PAK4 30 31
  • 91 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pak4 30
  • 86.89 (n)
Mouse
(Mus musculus)
Mammalia Pak4 30 17 31
  • 86.67 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PAK4 31
  • 82 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 42 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves PAK4 30 31
  • 76.62 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PAK4 31
  • 65 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia pak4 30
  • 65.98 (n)
Str.17438 30
African clawed frog
(Xenopus laevis)
Amphibia PAK5 30
Zebrafish
(Danio rerio)
Actinopterygii pak4 30 31
  • 67.43 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta mbt 30 31 32
  • 66.44 (n)
OneToMany
Pak3 32
  • 48 (a)
Worm
(Caenorhabditis elegans)
Secernentea C45B11.1a 32
  • 48 (a)
C45B11.1b 32
  • 48 (a)
pak-2