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

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 Breast Adenoma. Among its related pathways are Focal Adhesion and T cell receptor signaling pathway. 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 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

Additional gene information for PAK4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PAK4 Gene

Genomics for PAK4 Gene

GeneHancer (GH) Regulatory Elements for PAK4 Gene

Promoters and enhancers for PAK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J039125 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE dbSUPER 680.9 +1.6 1583 4.5 MLX FEZF1 DMAP1 YY1 SLC30A9 ZNF213 ZNF416 ZNF143 SP3 NFYC PAK4 PIR35823 HNRNPL FBL ENSG00000269172 ZNF780B ZNF780A ENSG00000269688 EID2B RN7SL566P
GH19J039124 Enhancer 0.7 ENCODE 657.6 -1.3 -1307 0.5 FOXA2 ZSCAN26 INSM2 ZNF175 TEAD3 ZNF664 RFX1 ZNF362 ZNF189 TEAD1 PAK4 PIR35823 ZNF780B HNRNPL FBL PLEKHG2 SUPT5H RN7SL566P ENSG00000269688 ZNF780A
GH19J039397 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 51.6 +281.3 281305 20 CLOCK MLX ZFP64 FEZF1 DMAP1 YBX1 IRF4 YY1 SLC30A9 ZNF213 ZFP36 PAF1 HNRNPL FBL ZNF780B SUPT5H RN7SL566P ZNF780A ENSG00000269688 AKT2
GH19J038647 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 50.6 -466.0 -465977 25.6 ZFP64 FEZF1 DMAP1 YY1 ZNF213 ZNF143 ZNF548 SP3 NFYC ZC3H11A ACTN4 HNRNPL ZFP30 ZNF607 ZNF781 ZNF573 SUPT5H ENSG00000267152 PAK4 RN7SL566P
GH19J039389 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 33.5 +265.0 265016 3.4 CLOCK ZFP64 FEZF1 DMAP1 YY1 ZNF213 E2F8 ZNF143 SP3 NFYC MED29 PAF1 HNRNPL EID2B PSMC4 PAK4 ZNF780B SUPT5H FBL RPS16
- 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 UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PAK4 gene promoter:
  • Hand1
  • E47
  • AREB6
  • NF-kappaB1
  • NF-kappaB2
  • NF-kappaB
  • CBF(2)
  • 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 FAM212A/INKA1 (PubMed:26607847).
    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

Post-translational modifications for PAK4 Gene

  • Autophosphorylated on serine residues when activated by CDC42/p21.
  • Phosphorylated on tyrosine residues upon stimulation of FGFR2.
  • Ubiquitination at Lys31
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for PAK4 Gene

Domains & Families for PAK4 Gene

Gene Families for PAK4 Gene

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

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:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by FAM212A/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: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 --
GO:0016301 kinase activity 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

miRNA for PAK4 Gene

miRTarBase miRNAs that target 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
cytosol 3
plasma membrane 2
cytoskeleton 2
nucleus 2
extracellular 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 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 IEA,IBA --
GO:0005794 Golgi apparatus TAS 9822598
GO:0005913 cell-cell adherens junction IDA 25468996
GO:0005925 focal adhesion HDA 21423176
genes like me logo Genes that share ontologies with PAK4: view

Pathways & Interactions for PAK4 Gene

genes like me logo Genes that share pathways with PAK4: view

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:0006468 protein phosphorylation IEA --
GO:0006915 apoptotic process TAS 20070256
GO:0007010 cytoskeleton organization TAS 20070256
GO:0007049 cell cycle IEA --
GO:0007165 signal transduction TAS 20070256
genes like me logo Genes that share ontologies with PAK4: view

Drugs & Compounds for PAK4 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Niacin Approved, Investigational Nutra Unknown, Agonist, Full agonist 946,946
Nicotinamide Approved, Investigational Nutra 942,946
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Folic Acid Approved, Vet_approved Nutra 4610
Guanosine triphosphate Experimental Pharma 0

(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
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 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

Unigene Clusters for PAK4 Gene

P21 protein (Cdc42/Rac)-activated kinase 4:
Representative Sequences:

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
ECgene alternative splicing isoforms for
PAK4

Expression for PAK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP 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

NURSA nuclear receptor signaling pathways regulating expression of PAK4 Gene:

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(4.3)
  • Eye(4.2)
  • Adrenal gland(2.1)
  • Lung(2.1)
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 34
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PAK4 34 33
  • 91.4 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PAK4 34 33
  • 91 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pak4 33
  • 86.89 (n)
mouse
(Mus musculus)
Mammalia Pak4 16 34 33
  • 86.67 (n)
oppossum
(Monodelphis domestica)
Mammalia PAK4 34
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 42 (a)
ManyToMany
chicken
(Gallus gallus)
Aves PAK4 34 33
  • 76.62 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PAK4 34
  • 65 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pak4 33
  • 65.98 (n)
Str.17438 33
African clawed frog
(Xenopus laevis)
Amphibia PAK5 33
zebrafish
(Danio rerio)
Actinopterygii pak4 34 33
  • 67.43 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta mbt 34 35 33
  • 66.44 (n)
OneToMany
Pak3 35
  • 48 (a)
worm
(Caenorhabditis elegans)
Secernentea C45B11.1b 35
  • 48 (a)
C45B11.1a 35
  • 48 (a)
pak-2 34
  • 47 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes STE20 34
  • 21 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10829 34
  • 42 (a)
OneToMany
Species where no ortholog for PAK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PAK4 Gene

ENSEMBL:
Gene Tree for PAK4 (if available)
TreeFam:
Gene Tree for PAK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PAK4: view image

Paralogs for PAK4 Gene

Paralogs for PAK4 Gene

genes like me logo Genes that share paralogs with PAK4: view

Variants for PAK4 Gene

Sequence variations from dbSNP and Humsavar for PAK4 Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs193920877 uncertain-significance, Malignant tumor of prostate 39,177,693(+) G/C coding_sequence_variant, missense_variant
rs1000102121 -- 39,173,483(+) T/C intron_variant
rs1000156501 -- 39,139,261(+) C/T genic_upstream_transcript_variant, intron_variant
rs1000161331 -- 39,177,481(+) G/C intron_variant
rs1000205428 -- 39,158,703(+) A/G genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for PAK4 Gene

Variant ID Type Subtype PubMed ID
dgv3528n100 CNV gain 25217958
esv2008944 CNV deletion 18987734
esv2369247 CNV deletion 18987734
esv2545161 CNV deletion 19546169
esv26259 CNV loss 19812545
esv2665610 CNV deletion 23128226
esv2674613 CNV deletion 23128226
esv2718547 CNV deletion 23290073
esv2718548 CNV deletion 23290073
esv2718549 CNV deletion 23290073
nsv1127683 CNV deletion 24896259
nsv1129624 CNV tandem duplication 24896259
nsv458571 CNV gain 19166990
nsv579508 CNV gain 21841781
nsv833829 CNV loss 17160897
nsv953571 CNV deletion 24416366

Variation tolerance for PAK4 Gene

Residual Variation Intolerance Score: 45.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.39; 42.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PAK4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PAK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PAK4 Gene

Disorders for PAK4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for PAK4 Gene - From: DISEASES