Tchem PAK4 Serine/threonine-protein kinase PAK 4

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• O96013
• B4DGG6
• Q8N4E1
• Q8NCH5
• Q8NDE3
• Q9BU33
• Q9ULS8

Gene Name

• PAK4

Ensembl ID

• ENST00000321944
• ENSP00000326864
• ENSG00000130669
• ENST00000358301
• ENSP00000351049
• ENST00000360442
• ENSP00000353625
• ENST00000593690
• ENSP00000469413
• ENST00000599386
• ENSP00000471157
• ENST00000599470
• ENSP00000470284

Symbol

• KIAA1142

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug perturbation	1
interacting protein	0.98
molecular function	0.96
transcription factor	0.77
hub protein	0.75

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste20 Family / Pakb Subfamily / Serine/threonine-protein Kinase Pak 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 191.42   (req: < 5)

Gene RIFs: 93   (req: <= 3)

Antibodies: 572   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 191.42   (req: >= 5)

Gene RIFs: 93   (req: > 3)

Antibodies: 572   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 83

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (83)

Explore Active Ligands

1 – 10 of 83

staurosporine

PAK4Tchem Kinase

pKd : 7.89

lestaurtinib

PAK4Tchem Kinase

pKd : 7.57

SID103905531

PAK4Tchem Kinase

pKi : 9.5

CHEMBL4465866

PAK4Tchem Kinase

pKd : 7.96

CHEMBL4576489

PAK4Tchem Kinase

pKd : 8.22

SID103904591

PAK4Tchem Kinase

pKi : 7.8

SID103904592

PAK4Tchem Kinase

pKi : 8

SID103904605

PAK4Tchem Kinase

pKi : 7.7

SID103904602

PAK4Tchem Kinase

pKi : 7.9

GSK690693

PAK4Tchem Kinase

pKd : 6.24

Protein-Protein Interactions (139)

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1 – 10 of 139

• See Interactions on String-DB

PAK5

Tchem

Family:  Kinase

Novelty:  0.02138632

p_int:  1

Score:  0.955

Data Source:  BioPlex,STRINGDB

ARHGEF11

Tbio

Novelty:  0.01942359

p_int:  0.999999597

p_ni:  2.79e-7

p_wrong:  1.25e-7

Score:  0.885

Data Source:  BioPlex,STRINGDB

CARMIL1

Tbio

Novelty:  0.04162135

p_int:  0.999998893

p_ni:  0.000001107

Score:  0.815

Data Source:  BioPlex,STRINGDB

PAK6

Tchem

Family:  Kinase

Novelty:  0.02050802

p_int:  0.999997283

p_ni:  1.7e-8

p_wrong:  0.000002701

Data Source:  BioPlex

GGNBP2

Tbio

Novelty:  0.03088714

p_int:  0.999633084

p_ni:  0.000004469

p_wrong:  0.000362447

Score:  0.514

Data Source:  BioPlex,STRINGDB

CDK6

Tclin

Family:  Kinase

Novelty:  0.00109319

p_int:  0.985539508

p_ni:  0.014460486

p_wrong:  5e-9

Score:  0.426

Data Source:  BioPlex,STRINGDB

TMPRSS11A

Tbio

Family:  Enzyme

Novelty:  0.06142295

p_int:  0.916365192

p_ni:  0.083634808

Score:  0.221

Data Source:  BioPlex,STRINGDB

DDX6

Tbio

Family:  Enzyme

Novelty:  0.01032357

p_int:  0.846719185

p_ni:  0.153280815

Score:  0.259

Data Source:  BioPlex,STRINGDB

KLHL42

Tdark

Novelty:  0.25822395

p_int:  0.839257567

p_ni:  0.160738531

p_wrong:  0.000003901

Score:  0.204

Data Source:  BioPlex,STRINGDB

MTUS2

Tbio

Novelty:  0.13504593

p_int:  0.754088358

p_ni:  0.245911642

Data Source:  BioPlex

Nearest Tclin Targets (10)

Explore Nearest Tclin Targets

Upstream (8)

Downstream (2)

1 – 5 of 8

PIK3CA

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  9

1: Axon guidance

2: Focal adhesion

3: T cell receptor signaling pathway

4: Renal cell carcinoma

more:  5 more common pathways

PIK3CD

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  9

1: Axon guidance

2: Focal adhesion

3: T cell receptor signaling pathway

4: Renal cell carcinoma

more:  5 more common pathways

CHRM1

Tclin

Family:  GPCR

KEGG Distance:  2

Common Pathways:  1

1: Regulation of actin cytoskeleton

CHRM2

Tclin

Family:  GPCR

KEGG Distance:  2

Common Pathways:  1

1: Regulation of actin cytoskeleton

CHRM5

Tclin

Family:  GPCR

KEGG Distance:  2

Common Pathways:  1

1: Regulation of actin cytoskeleton

Pathways (34)

Reactome (4)

KEGG (9)

PathwayCommons (10)

WikiPathways (11)

Activation of RAC1 (R-HSA-428540)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of RAC1	13 targets	R-HSA-428540
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Signaling by ROBO receptors	220 targets	R-HSA-376176

Name	Explore in Pharos	Explore in Source
Activation of RAC1	13 targets	R-HSA-428540
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
Signaling by ROBO receptors	220 targets	R-HSA-376176

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (24)

Functions (5)

Components (4)

Processes (15)

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GO Term	Evidence	Assigned by
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
cadherin binding involved in cell-cell adhesion	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
Rac GTPase binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein kinase activity	Non-traceable Author Statement (NAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (9)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
chronic hepatitis C virus infection	EFO_0004220	7	3	0	2.2	91.3
remission	EFO_0009785	3	1	0	2.1	84.2
hepatitis C virus infection	EFO_0003047	3	1	0	2.1	84.2
mitochondrial heteroplasmy measurement	EFO_0600008	1	1	1		56.6
viral load	EFO_0010125	1	1	1		49.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 9

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
chronic hepatitis C virus infection	EFO_0004220	0	2.2	91.3
remission	EFO_0009785	0	2.1	84.2
hepatitis C virus infection	EFO_0003047	0	2.1	84.2
mitochondrial heteroplasmy measurement	EFO_0600008	1		56.6
viral load	EFO_0010125	1		49.5

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Apoptosis
ATP-binding
Cell cycle
Complete proteome
Cytoplasm
Kinase
Methylation
Nucleotide-binding

GWAS Trait Find Similar Targets

No Header	No Header
chronic hepatitis C virus infection
hepatitis C virus infection
hepatocellular carcinoma
intelligence
mathematical ability
mitochondrial heteroplasmy measurement
ovarian mucinous adenocarcinoma
remission
viral load

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
integument phenotype
mortality/aging
muscle phenotype
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	p21 (RAC1) activated kinase 4		696676
Mouse	p21 (RAC1) activated kinase 4	MGI:1917834	70584
Rat	p21 (RAC1) activated kinase 4	RGD:1307705	292756
Dog	p21 (RAC1) activated kinase 4	VGNC:53528	484513
Horse	p21 (RAC1) activated kinase 4 [Source:HGNC Symbol;Acc:HGNC:16059]

Species	Name	OMA	EggNOG	Inparanoid
Macaque	p21 (RAC1) activated kinase 4
Mouse	p21 (RAC1) activated kinase 4
Rat	p21 (RAC1) activated kinase 4
Dog	p21 (RAC1) activated kinase 4
Horse	p21 (RAC1) activated kinase 4 [Source:HGNC Symbol;Acc:HGNC:16059]

Publication Statistics

PubMed Score 191.42

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PubTator Score 98.89

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Related Publications

Text Mined References (121)

GeneRif Annotations (93)

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PMID	Year	Title