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    PAK4 p21 (RAC1) activated kinase 4 [ Homo sapiens (human) ]

    Gene ID: 10298, updated on 17-Jun-2019

    Summary

    Official Symbol
    PAK4provided by HGNC
    Official Full Name
    p21 (RAC1) activated kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:16059
    See related
    Ensembl:ENSG00000130669 MIM:605451
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    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]
    Expression
    Ubiquitous expression in prostate (RPKM 14.9), kidney (RPKM 12.6) and 25 other tissues See more
    Orthologs

    Genomic context

    See PAK4 in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    109.20190607 current GRCh38.p13 (GCF_000001405.39) 19 NC_000019.10 (39125786..39182816)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (39616417..39670046)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene F-box protein 27 Neighboring gene acid phosphatase 7, tartrate resistant (putative) Neighboring gene non-specific cytotoxic cell receptor protein 1 homolog (zebrafish) Neighboring gene syncollin

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • Activation of Rac, organism-specific biosystem (from REACTOME)
      Activation of Rac, organism-specific biosystemA low level of Rac activity is essential to maintain axon outgrowth and Robo activation recruits Sos, a dual specificity GEF to the plasma membrane via Dock to activate Rac during midline repulsion.
    • Axon guidance, organism-specific biosystem (from KEGG)
      Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
    • Axon guidance, conserved biosystem (from KEGG)
      Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
    • Axon guidance, organism-specific biosystem (from REACTOME)
      Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
    • CDC42 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      CDC42 signaling events, organism-specific biosystem
      CDC42 signaling events
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • ErbB Signaling Pathway, organism-specific biosystem (from WikiPathways)
      ErbB Signaling Pathway, organism-specific biosystemThe ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with ...
    • ErbB signaling pathway, organism-specific biosystem (from KEGG)
      ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • ErbB signaling pathway, conserved biosystem (from KEGG)
      ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • FGF signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      FGF signaling pathway, organism-specific biosystem
      FGF signaling pathway
    • Focal Adhesion, organism-specific biosystem (from WikiPathways)
      Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, organism-specific biosystem (from KEGG)
      Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, conserved biosystem (from KEGG)
      Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Integrin-mediated Cell Adhesion, organism-specific biosystem (from WikiPathways)
      Integrin-mediated Cell Adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
    • MicroRNAs in cancer, organism-specific biosystem (from KEGG)
      MicroRNAs in cancer, organism-specific biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
    • MicroRNAs in cancer, conserved biosystem (from KEGG)
      MicroRNAs in cancer, conserved biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
    • Ras signaling pathway, organism-specific biosystem (from KEGG)
      Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
    • Regulation of Actin Cytoskeleton, organism-specific biosystem (from WikiPathways)
      Regulation of Actin Cytoskeleton, organism-specific biosystemhttp://www.genome.jp/kegg/pathway/hsa/hsa04810.html
    • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
      Regulation of actin cytoskeleton, organism-specific biosystem
      Regulation of actin cytoskeleton
    • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
      Regulation of actin cytoskeleton, conserved biosystem
      Regulation of actin cytoskeleton
    • Renal cell carcinoma, organism-specific biosystem (from KEGG)
      Renal cell carcinoma, organism-specific biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
    • Renal cell carcinoma, conserved biosystem (from KEGG)
      Renal cell carcinoma, conserved biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
    • Signaling by Robo receptor, organism-specific biosystem (from REACTOME)
      Signaling by Robo receptor, organism-specific biosystemThe Roundabout (Robo) family encodes transmembrane receptors that regulate axonal guidance and cell migration. The major function of the Robo receptors is to mediate repulsion of the navigating growt...
    • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
      Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    Rac GTPase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    cadherin binding involved in cell-cell adhesion HDA PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein serine/threonine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    activation of protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    cell migration TAS
    Traceable Author Statement
    more info
    PubMed 
    cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    cell-cell adhesion IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to organic cyclic compound IEA
    Inferred from Electronic Annotation
    more info
     
    cytoskeleton organization TAS
    Traceable Author Statement
    more info
    PubMed 
    dendritic spine development IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of endothelial cell apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    regulation of cell growth TAS
    Traceable Author Statement
    more info
    PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    signal transduction by protein phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    stress-activated protein kinase signaling cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Component Evidence Code Pubs
    Golgi apparatus TAS
    Traceable Author Statement
    more info
    PubMed 
    cell-cell adherens junction HDA PubMed 
    cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    focal adhesion HDA PubMed 

    General protein information

    Preferred Names
    serine/threonine-protein kinase PAK 4
    Names
    p21 protein (Cdc42/Rac)-activated kinase 4
    p21(CDKN1A)-activated kinase 4
    protein kinase related to S. cerevisiae STE20, effector for Cdc42Hs
    NP_001014831.1
    NP_001014832.1
    NP_001014834.1
    NP_001014835.1
    NP_005875.1
    XP_011524618.1
    XP_011524619.1
    XP_011524620.1
    XP_011524621.1
    XP_011524622.1
    XP_024307082.1

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_047118.1 RefSeqGene

      Range
      5001..58627
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001014831.3NP_001014831.1  serine/threonine-protein kinase PAK 4 isoform 1

      See identical proteins and their annotated locations for NP_001014831.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an additional segment in the 5' UTR, and encodes the same isoform (1), as compared to variant 1.
      Source sequence(s)
      AB032968, AC011443, BC025282, BG773480
      Consensus CDS
      CCDS12528.1
      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Related
      ENSP00000469413.1, ENST00000593690.5
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
    2. NM_001014832.2NP_001014832.1  serine/threonine-protein kinase PAK 4 isoform 1

      See identical proteins and their annotated locations for NP_001014832.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon in the 5' UTR, and encodes the same isoform (1), as compared to variant 1.
      Source sequence(s)
      AB032968, AC011443, BC011368, BC025282, BG773480
      Consensus CDS
      CCDS12528.1
      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Related
      ENSP00000351049.2, ENST00000358301.7
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
    3. NM_001014834.3NP_001014834.1  serine/threonine-protein kinase PAK 4 isoform 2

      See identical proteins and their annotated locations for NP_001014834.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an exon in the 5' UTR and an in-frame exon in the coding region, as compared to variant 1. The encoded isoform (2) thus lacks an internal segment, as compared to isoform 1.
      Source sequence(s)
      AB032968, AC011443, AL834236, BG773480
      Consensus CDS
      CCDS33019.1
      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0L8
      Related
      ENSP00000470284.1, ENST00000599470.5
      Conserved Domains (2) summary
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
      cl21453
      Location:147438
      PKc_like; Protein Kinases, catalytic domain
    4. NM_001014835.2NP_001014835.1  serine/threonine-protein kinase PAK 4 isoform 2

      See identical proteins and their annotated locations for NP_001014835.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an in-frame exon in the coding region, as compared to variant 1. The encoded isoform (2) thus lacks an internal segment, as compared to isoform 1.
      Source sequence(s)
      AB032968, AC011443, BG773480
      Consensus CDS
      CCDS33019.1
      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0L8
      Related
      ENSP00000471157.1, ENST00000599386.5
      Conserved Domains (2) summary
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
      cl21453
      Location:147438
      PKc_like; Protein Kinases, catalytic domain
    5. NM_005884.4NP_005875.1  serine/threonine-protein kinase PAK 4 isoform 1

      See identical proteins and their annotated locations for NP_005875.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AB032968, AC011443, AF005046, BG773480
      Consensus CDS
      CCDS12528.1
      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p13 Primary Assembly

      Range
      39125786..39182816
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011526316.1XP_011524618.1  serine/threonine-protein kinase PAK 4 isoform X1

      See identical proteins and their annotated locations for XP_011524618.1

      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Related
      ENSP00000326864.4, ENST00000321944.8
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
    2. XM_011526320.1XP_011524622.1  serine/threonine-protein kinase PAK 4 isoform X2

      See identical proteins and their annotated locations for XP_011524622.1

      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0L8
      Conserved Domains (2) summary
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
      cl21453
      Location:147438
      PKc_like; Protein Kinases, catalytic domain
    3. XM_011526317.2XP_011524619.1  serine/threonine-protein kinase PAK 4 isoform X1

      See identical proteins and their annotated locations for XP_011524619.1

      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
    4. XM_024451314.1XP_024307082.1  serine/threonine-protein kinase PAK 4 isoform X2

      Conserved Domains (2) summary
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
      cl21453
      Location:147438
      PKc_like; Protein Kinases, catalytic domain
    5. XM_011526318.2XP_011524620.1  serine/threonine-protein kinase PAK 4 isoform X1

      See identical proteins and their annotated locations for XP_011524620.1

      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
    6. XM_011526319.2XP_011524621.1  serine/threonine-protein kinase PAK 4 isoform X1

      See identical proteins and their annotated locations for XP_011524621.1

      UniProtKB/Swiss-Prot
      O96013
      UniProtKB/TrEMBL
      A0A024R0J1
      Conserved Domains (2) summary
      cd06657
      Location:300591
      STKc_PAK4; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4
      cd01093
      Location:1055
      CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001014833.1: Suppressed sequence

      Description
      NM_001014833.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
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