PAK6 Gene

Name	p21 protein (Cdc42/Rac)-activated kinase 6
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPAK6, a member of the class II p21‐activated kinases, has emerged as a multifaceted regulator in cancer biology. In prostate cancer, it interacts directly with the androgen receptor (AR) to modulate AR phosphorylation, ubiquitin‐mediated degradation, and nuclear translocation. These processes culminate in altered cell motility, invasion, and tumorigenesis, with evidence showing that PAK6 can suppress prostate tumor growth as well as influence therapeutic responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond AR-related mechanisms, PAK6 participates in broader cell signaling events. Its kinase activity is modulated by stress-related MAP kinase pathways—being activated by MKK6 and the p38 MAP kinase—and it has been found to interact with proteins such as LRRK2 to promote neurite outgrowth. In epithelial cells, PAK6 localizes to cell–cell adhesions where it associates with junctional components (including IQGAP1 and phosphorylated β-catenin) to drive junction disassembly and facilitate cell colony escape."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPAK6 is also implicated in chemoresistance and tumor progression in several cancers. In colon and gastric cancers, overexpression of PAK6 correlates with increased tumor aggressiveness and reduced sensitivity to agents such as 5-fluorouracil–based chemotherapy. Moreover, studies in non-small cell lung cancer have linked cigarette smoke exposure to enhanced PAK6 activation that promotes cell proliferation, migration, and invasion. In hematological malignancies, microRNA-mediated targeting of PAK6 (e.g. by miR-185 and miR-429) has been shown to suppress drug resistance and reduce the pool of leukemic stem cells, highlighting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIntriguingly, PAK6 exerts roles that extend into the regulation of mitochondrial function and mitosis. In prostate cancer cells, PAK6 localizes to the mitochondrial inner membrane where it modulates the SIRT4–ANT2 complex, ultimately influencing apoptotic signaling. In hepatocellular carcinoma, several studies reveal that PAK6 can act in a tumor-suppressive manner by regulating mitotic spindle formation—partly through modulation of Eg5 expression—and through epigenetic mechanisms involving promoter hypermethylation. Additionally, in non-cancer contexts such as intervertebral disc degeneration, miR-4306-mediated suppression of PAK6 contributes to enhanced extracellular matrix synthesis, cell survival, and autophagy in nucleus pulposus cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yu-jing Han, Zheng-wen An, Jin-xing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Cloning of human PAK6 cDNA, preparation of anti-PAK6 polyclonal antibody and PAK6 expression in prostate cancer]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nan Fang Yi Ke Da Xue Xue Bao (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17584649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17584649"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ramneet Kaur, Xin Yuan, Michael L Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.20787"}], "href": "https://doi.org/10.1002/pros.20787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18642328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18642328"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tong Liu, Yang Li, Hui Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.384289"}], "href": "https://doi.org/10.1074/jbc.M112.384289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23132866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23132866"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xia Liu, Jennifer Busby, Ciny John, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct interaction between AR and PAK6 in androgen-stimulated PAK6 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0077367"}], "href": "https://doi.org/10.1371/journal.pone.0077367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24130878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24130878"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chunhui Liu, Lei Zhang, Yeqing Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA‑328 directly targets p21‑activated protein kinase 6 inhibiting prostate cancer proliferation and enhancing docetaxel sensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2015.4390"}], "href": "https://doi.org/10.3892/mmr.2015.4390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26459798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26459798"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ramneet Kaur, Xia Liu, Ole Gjoerup, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406701200"}], "href": "https://doi.org/10.1074/jbc.M406701200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15550393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15550393"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sally Fram, Helen King, David B Sacks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-013-1528-5"}], "href": "https://doi.org/10.1007/s00018-013-1528-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24352566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24352566"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Laura Civiero, Maria Daniela Cirnaru, Alexandra Beilina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jnc.13369"}], "href": "https://doi.org/10.1111/jnc.13369"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26375402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26375402"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Elizabeth M Morse, Xiaowen Sun, Jordan R Olberding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.177493"}], "href": "https://doi.org/10.1242/jcs.177493"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26598554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26598554"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Charlotte H Durkin, Flavia Leite, João V Cordeiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2017.04.010"}], "href": "https://doi.org/10.1016/j.devcel.2017.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28486133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28486133"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jian Chen, Huijun Lu, Dongwang Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2803"}], "href": "https://doi.org/10.18632/oncotarget.2803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25426562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25426562"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xiangyang Tian, Zibai Wei, Jia Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The miR-185/PAK6 axis predicts therapy response and regulates survival of drug-resistant leukemic stem cells in CML."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.2019003636"}], "href": "https://doi.org/10.1182/blood.2019003636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32270193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32270193"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Eun-Ju Lee, Michael Mcclelland, Yipeng Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Expression and prognostic significance of p21-activated kinase 6 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Surg Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jss.2014.01.049"}], "href": "https://doi.org/10.1016/j.jss.2014.01.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24576777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24576777"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Weisi Liu, Yidong Liu, Haiou Liu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "p21-activated kinase 6 controls mitosis and hepatocellular carcinoma progression by regulating Eg5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2020.118888"}], "href": "https://doi.org/10.1016/j.bbamcr.2020.118888"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33098954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33098954"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Dongdong Wang, Ji Zhu, Yuanqing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of the miR-4306/PAK6 axis in degenerative nucleus pulposus cells in human intervertebral disc degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2022.110528"}], "href": "https://doi.org/10.1016/j.cellsig.2022.110528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36423859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36423859"}]}]}]}
Synonyms	PAK5
Proteins	PAK6_HUMAN
NCBI Gene ID	56924
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PAK6 has 4,281 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for PAK6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PAK6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PAK6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PAK6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PAK6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PAK6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PAK6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving PAK6 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PAK6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PAK6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PAK6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PAK6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PAK6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PAK6 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PAK6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PAK6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PAK6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PAK6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PAK6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PAK6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PAK6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PAK6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PAK6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PAK6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PAK6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PAK6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PAK6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PAK6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PAK6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PAK6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PAK6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PAK6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PAK6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PAK6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PAK6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PAK6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PAK6 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PAK6 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PAK6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PAK6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PAK6 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PAK6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.