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    PAK6 p21 (RAC1) activated kinase 6 [ Homo sapiens (human) ]

    Gene ID: 56924, updated on 5-Mar-2024

    Summary

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    Official Symbol
    PAK6provided by HGNC
    Official Full Name
    p21 (RAC1) activated kinase 6provided by HGNC
    Primary source
    HGNC:HGNC:16061
    See related
    Ensembl:ENSG00000137843 MIM:608110; AllianceGenome:HGNC:16061
    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
    Also known as
    PAK5
    Summary
    This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
    Expression
    Broad expression in testis (RPKM 8.7), brain (RPKM 8.5) and 14 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    15q15.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (40239063..40277487)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (38045955..38084404)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (40531264..40569688)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40428847-40429621 Neighboring gene MT-ND4 pseudogene 37 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40449670-40450530 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9236 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9237 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40453661-40454425 Neighboring gene uncharacterized LOC107984763 Neighboring gene BUB1 mitotic checkpoint serine/threonine kinase B Neighboring gene MPRA-validated peak2300 silencer Neighboring gene BUB1B-PAK6 readthrough Neighboring gene MPRA-validated peak2301 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40520705-40521206 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40534525-40535024 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40537349-40537850 Neighboring gene Sharpr-MPRA regulatory region 12967 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6319 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9238 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40548820-40549617 Neighboring gene PAK6 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40564915-40565416 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40566138-40566638 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40572232-40573016 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6320 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6321 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6322 Neighboring gene ankyrin repeat domain 63 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40583508-40584053 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40584054-40584598 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9239 Neighboring gene phospholipase C beta 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40594309-40595118

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex. Li T, et al. Theranostics, 2020. PMID 32194820, Free PMC Article
    2. Prognostic and Predictive Value of p21-activated Kinase 6 Associated Support Vector Machine Classifier in Gastric Cancer Treated by 5-fluorouracil/Oxaliplatin Chemotherapy. Jiang Y, et al. EBioMedicine, 2017 Aug. PMID 28687498, Free PMC Article
    3. Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells. Raja R, et al. Oncotarget, 2016 Sep 20. PMID 27542207, Free PMC Article
    4. Tumor Suppressive Function of p21-activated Kinase 6 in Hepatocellular Carcinoma. Liu W, et al. J Biol Chem, 2015 Nov 20. PMID 26442588, Free PMC Article
    5. PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy. Chen J, et al. Oncotarget, 2015 Jan 1. PMID 25426562, Free PMC Article

    See all (70) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The role of the miR-4306/PAK6 axis in degenerative nucleus pulposus cells in human intervertebral disc degeneration.
      Title: The role of the miR-4306/PAK6 axis in degenerative nucleus pulposus cells in human intervertebral disc degeneration.
    2. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis.
      Title: Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis.
    3. Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex.
      Title: Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex.
    4. p21-activated kinase 6 controls mitosis and hepatocellular carcinoma progression by regulating Eg5.
      Title: p21-activated kinase 6 controls mitosis and hepatocellular carcinoma progression by regulating Eg5.
    5. The miR-185/PAK6 axis predicts therapy response and regulates survival of drug-resistant leukemic stem cells in CML.
      Title: The miR-185/PAK6 axis predicts therapy response and regulates survival of drug-resistant leukemic stem cells in CML.
    6. inhibition of PAK6 leads to reduction in cell proliferation, migration and invasion of cigarette smoke treated non-small cell lung cancer cells
      Title: Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells.
    7. Study shows that high PAK6 expression is associated with poor prognosis and increased chemoresistance to 5-FU/oxaliplatin chemotherapy of gastric tumor.
      Title: Prognostic and Predictive Value of p21-activated Kinase 6 Associated Support Vector Machine Classifier in Gastric Cancer Treated by 5-fluorouracil/Oxaliplatin Chemotherapy.
    8. RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing
      Title: RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.
    9. PAK6 localization to cell-cell adhesions is Cdc42-dependent
      Title: PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape.
    10. p21-activated kinase 6 (PAK6) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease
      Title: Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Readthrough BUB1B-PAK6

    Readthrough gene: BUB1B-PAK6, Included gene: BUB1B

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cadherin binding HDA PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cytoskeleton organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in memory IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron projection arborization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron projection extension IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of DNA-templated transcription TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cell junction IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in fibrillar center IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in postsynaptic density IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein kinase PAK 6
    Names
    p21 protein (Cdc42/Rac)-activated kinase 6
    p21(CDKN1A)-activated kinase 6
    NP_001263646.1
    NP_001263647.1
    NP_001382359.1
    NP_001382360.1
    NP_064553.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_033169.1 RefSeqGene

      Range
      26636..65060
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001276717.1 → NP_001263646.1  serine/threonine-protein kinase PAK 6 isoform 1

      See identical proteins and their annotated locations for NP_001263646.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and the 3' UTR, compared to variant 1. Variants 1 and 4 encode the same isoform (1).
      Source sequence(s)
      BC035596, DA191028
      UniProtKB/Swiss-Prot
      A8K2G2, B3KYB0, G5E9R2, Q9NQU5
      Related
      ENSP00000439597.2, ENST00000542403.3
      Conserved Domains (2) summary
      cd06659
      Location:385 → 681
      STKc_PAK6; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6
      pfam00786
      Location:11 → 67
      PBD; P21-Rho-binding domain

    2. NM_001276718.2 → NP_001263647.1  serine/threonine-protein kinase PAK 6 isoform 2

      See identical proteins and their annotated locations for NP_001263647.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC020658, AK026592, AK131522, BC035596
      Consensus CDS
      CCDS61590.1
      UniProtKB/Swiss-Prot
      Q9NQU5
      Related
      ENSP00000409465.2, ENST00000455577.6
      Conserved Domains (3) summary
      smart00220
      Location:412 → 613
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam00786
      Location:11 → 63
      PBD; P21-Rho-binding domain
      cl21453
      Location:385 → 636
      PKc_like; Protein Kinases, catalytic domain

    3. NM_001395430.1 → NP_001382359.1  serine/threonine-protein kinase PAK 6 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC020658
      UniProtKB/Swiss-Prot
      A8K2G2, B3KYB0, G5E9R2, Q9NQU5
      Related
      ENSP00000453858.1, ENST00000560346.6
      Conserved Domains (2) summary
      cd06659
      Location:385 → 681
      STKc_PAK6; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6
      pfam00786
      Location:11 → 67
      PBD; P21-Rho-binding domain

    4. NM_001395431.1 → NP_001382360.1  serine/threonine-protein kinase PAK 6 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC020658
      UniProtKB/Swiss-Prot
      A8K2G2, B3KYB0, G5E9R2, Q9NQU5
      Conserved Domains (2) summary
      cd06659
      Location:385 → 681
      STKc_PAK6; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6
      pfam00786
      Location:11 → 67
      PBD; P21-Rho-binding domain

    5. NM_020168.6 → NP_064553.1  serine/threonine-protein kinase PAK 6 isoform 1

      See identical proteins and their annotated locations for NP_064553.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1. Variants 1 and 4 encode the same isoform (1).
      Source sequence(s)
      AC020658
      UniProtKB/Swiss-Prot
      A8K2G2, B3KYB0, G5E9R2, Q9NQU5
      Related
      ENSP00000260404.4, ENST00000260404.8
      Conserved Domains (2) summary
      cd06659
      Location:385 → 681
      STKc_PAK6; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6
      pfam00786
      Location:11 → 67
      PBD; P21-Rho-binding domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      40239063..40277487
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      38045955..38084404
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NQU5.1 GenPept UniProtKB/Swiss-Prot:Q9NQU5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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