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Protein PAK7 PDB 2f57.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesPAK5, PAK7, p21 (RAC1) activated kinase 7, p21 (RAC1) activated kinase 5
External IDsOMIM: 608038 MGI: 1920334 HomoloGene: 22211 GeneCards: PAK5
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 20: 9.54 – 9.84 MbChr 2: 135.92 – 136.23 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Serine/threonine-protein kinase PAK 5 is an enzyme that in humans is encoded by the PAK5 gene.[5][6][7]

The PAK5 enzyme is one of three members of Group II PAK family of serine/threonine kinases,[8][9] and evolutionary conserved across species.[10]


The PAK5 was initially cloned as a brain-specific kinase with a predominant expression in brain with a suggested role in neurite growth in neuronal cells.[8][9] Selectivity of PAK5 signaling was recognized by its ability to stimulate the JNK kinase but not p38 or ERK kinases.[9]

Gene and spliced variants[edit]

The PAK5 gene, the longest among the PAK family, contains a total of 12 exons of which four exons are for 5’-UTR and remaining 8 exons for protein coding(Gene from review). Alternative exon splicing of the PAK5 gene generates three transcripts, and one of the transcript encodes a 719 amino acids long protein(Gene from review). The exon splicing of the murine PAK5 gene generates three transcripts, two of which code an identical 719 amino acids long polypeptide while the 2.0-kb transcript is a non-coding RNA with retained intron.

Protein domains[edit]

Similar to PAK4, PAK5 consists of a kinase, a CDC42/Rac1 interactive binding (CRIB) motif.[11]


The protein encoded by this gene is a member of the PAK family of Ser/Thr protein kinases. PAK family members are known to be effectors of Rac/Cdc42 GTPases, which have been implicated in the regulation of cytoskeletal dynamics, proliferation, and cell survival signaling. This kinase contains a CDC42/Rac1 interactive binding (CRIB) motif, and has been shown to bind CDC42 in the presence of GTP.

This kinase is predominantly expressed in brain. It is capable of promoting neurite outgrowth, and thus may play a role in neurite development. This kinase is associated with microtubule networks and induces microtubule stabilization. The subcellular localization of this kinase is tightly regulated during cell cycle progression. Alternatively spliced transcript variants encoding the same protein have been described.[7]

Genetic deletion of PAK5 with or without PAK6 deletion in mice has been shown to be associated with a defective locomotion, memory, and learning.[12][13] PAK5 is co-expressed with DISC1, a psychosis risk gene, and the pathway is likely to be involved in modulating synapse plasticity.[14] Physiological level of PAK5 is linked with an overall physical activity in mice as PAK5 deletion in mice has been shown to be associated with an increased activity upon amphetamine stimulation.[15] PAK5 has been also thought to be one of genetic variants regulating gene expression (eQTL) and its expression associates with an inhibited glucose-regulated secretion of insulin in INS1 cells.[16]

Upstream regulators[edit]

PAK5 expression is positively regulated by Aurora-A and both PAK5 and Aurora-A are co-upregulated in esophageal squamous carcinoma.[17] The levels of PAK5 are regulated by miR-129 in hepatocacinoma cancer cells,[18] and by the binding of the long non-coding RNA Colorectal neoplasia differentially expressed (CRNDE) to miR-186 in glioma cells.[19]

Downstream targets[edit]

PAK5 phosphorylates Pacsin-1 and Synaptojanin-1 and regulates synaptic vesicle trafficking.[20] PAK5-mediated phosphorylation of GATA1 at S161 and S187 contributes to Epithelial-mesenchymal transition.[21] PAK5 phosphorylation of p120-catenin at S288 plays a role in cytoskeleton remodeling.[22] In addition to the cytoplasm, the PAK5 also localizes in mitochondria and phosphorylates BAD at S112.[23] PAK5 inhibits the MARK2/Par1 activity and modulates microtubules dynamics.[24]

Clinical significance[edit]

PAK5 levels are upregulated in osteosarcoma,[25] hepatocellular carcinomas,[26] gastric cancer,[27] glioma,[28] esophageal squamous cell cancer,[29] colon cancer,[30] ovarian cancer,[31] and breast cancer.[32] There are also examples of gain-of-function activating PAK5 mutations in non-small-cell lung cancer lung cancer.[33] PAK5 promotes the cell survival and sensitivity of cancer cells to chemotherapy.[17][31][34][35]



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  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039913 - Ensembl, May 2017
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  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  9. ^ a b c Pandey A, Dan I, Kristiansen TZ, Watanabe NM, Voldby J, Kajikawa E, Khosravi-Far R, Blagoev B, Mann M (May 2002). "Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain". Oncogene. 21 (24): 3939–48. doi:10.1038/sj.onc.1205478. PMID 12032833.
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  15. ^ Furnari MA, Jobes ML, Nekrasova T, Minden A, Wagner GC (April 2014). "Differential sensitivity of Pak5, Pak6, and Pak5/Pak6 double-knockout mice to the stimulant effects of amphetamine and exercise-induced alterations in body weight". Nutritional Neuroscience. 17 (3): 109–15. doi:10.1179/1476830513Y.0000000072. PMC 4365912. PMID 23710594.
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  17. ^ a b He S, Feng M, Liu M, Yang S, Yan S, Zhang W, Wang Z, Hu C, Xu Q, Chen L, Zhu H, Xu N (1 December 2014). "P21-activated kinase 7 mediates cisplatin-resistance of esophageal squamous carcinoma cells with Aurora-A overexpression". PLOS ONE. 9 (12): e113989. doi:10.1371/journal.pone.0113989. PMC 4250179. PMID 25436453.
  18. ^ Zhai J, Qu S, Li X, Zhong J, Chen X, Qu Z, Wu D (August 2015). "miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma". Biochemical and Biophysical Research Communications. 464 (1): 161–7. doi:10.1016/j.bbrc.2015.06.108. PMID 26116538.
  19. ^ Zheng J, Li XD, Wang P, Liu XB, Xue YX, Hu Y, Li Z, Li ZQ, Wang ZH, Liu YH (September 2015). "CRNDE affects the malignant biological characteristics of human glioma stem cells by negatively regulating miR-186". Oncotarget. 6 (28): 25339–55. doi:10.18632/oncotarget.4509. PMC 4694835. PMID 26231038.
  20. ^ Strochlic TI, Concilio S, Viaud J, Eberwine RA, Wong LE, Minden A, Turk BE, Plomann M, Peterson JR (March 2012). "Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking". Proceedings of the National Academy of Sciences of the United States of America. 109 (11): 4116–21. doi:10.1073/pnas.1116560109. PMC 3306725. PMID 22371566.
  21. ^ Li Y, Ke Q, Shao Y, Zhu G, Li Y, Geng N, Jin F, Li F (February 2015). "GATA1 induces epithelial-mesenchymal transition in breast cancer cells through PAK5 oncogenic signaling". Oncotarget. 6 (6): 4345–56. doi:10.18632/oncotarget.2999. PMC 4414194. PMID 25726523.
  22. ^ Wong LE, Reynolds AB, Dissanayaka NT, Minden A (August 2010). "p120-catenin is a binding partner and substrate for Group B Pak kinases". Journal of Cellular Biochemistry. 110 (5): 1244–54. doi:10.1002/jcb.22639. PMID 20564219. S2CID 24567609.
  23. ^ Cotteret S, Jaffer ZM, Beeser A, Chernoff J (August 2003). "p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD". Molecular and Cellular Biology. 23 (16): 5526–39. doi:10.1128/mcb.23.16.5526-5539.2003. PMC 166342. PMID 12897128.
  24. ^ Matenia D, Griesshaber B, Li XY, Thiessen A, Johne C, Jiao J, Mandelkow E, Mandelkow EM (September 2005). "PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable microtubules and dynamic actin". Molecular Biology of the Cell. 16 (9): 4410–22. doi:10.1091/mbc.E05-01-0081. PMC 1196348. PMID 16014608.
  25. ^ Han K, Zhou Y, Gan ZH, Qi WX, Zhang JJ, Fen T, Meng W, Jiang L, Shen Z, Min DL (December 2014). "p21-activated kinase 7 is an oncogene in human osteosarcoma". Cell Biology International. 38 (12): 1394–402. doi:10.1002/cbin.10351. PMC 4410679. PMID 25052921.
  26. ^ Fang ZP, Jiang BG, Gu XF, Zhao B, Ge RL, Zhang FB (January 2014). "P21-activated kinase 5 plays essential roles in the proliferation and tumorigenicity of human hepatocellular carcinoma". Acta Pharmacologica Sinica. 35 (1): 82–8. doi:10.1038/aps.2013.31. PMC 4075737. PMID 23685956.
  27. ^ Gu J, Li K, Li M, Wu X, Zhang L, Ding Q, Wu W, Yang J, Mu J, Wen H, Ding Q, Lu J, Hao Y, Chen L, Zhang W, Li S, Liu Y (January 2013). "A role for p21-activated kinase 7 in the development of gastric cancer". The FEBS Journal. 280 (1): 46–55. doi:10.1111/febs.12048. PMID 23106939. S2CID 38130015.
  28. ^ Gu X, Wang C, Wang X, Ma G, Li Y, Cui L, Chen Y, Zhao B, Li K (12 January 2015). "Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5". International Journal of Biological Sciences. 11 (2): 230–7. doi:10.7150/ijbs.9193. PMC 4308408. PMID 25632266.
  29. ^ He S, Liu M, Zhang W, Xu N, Zhu H (2016). "Over expression of p21-activated kinase 7 associates with lymph node metastasis in esophageal squamous cell cancers". Cancer Biomarkers. 16 (2): 203–9. doi:10.3233/CBM-150557. PMID 26682509.
  30. ^ Gong W, An Z, Wang Y, Pan X, Fang W, Jiang B, Zhang H (August 2009). "P21-activated kinase 5 is overexpressed during colorectal cancer progression and regulates colorectal carcinoma cell adhesion and migration". International Journal of Cancer. 125 (3): 548–55. doi:10.1002/ijc.24428. PMID 19415746. S2CID 42711385.
  31. ^ a b Li D, Yao X, Zhang P (November 2013). "The overexpression of P21-activated kinase 5 (PAK5) promotes paclitaxel-chemoresistance of epithelial ovarian cancer". Molecular and Cellular Biochemistry. 383 (1–2): 191–9. doi:10.1007/s11010-013-1767-7. PMID 23877225. S2CID 5938617.
  32. ^ Wang XX, Cheng Q, Zhang SN, Qian HY, Wu JX, Tian H, Pei DS, Zheng JN (October 2013). "PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell". Tumour Biology. 34 (5): 2721–9. doi:10.1007/s13277-013-0824-x. PMID 23696025. S2CID 15521185.
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  34. ^ Wang X, Gong W, Qing H, Geng Y, Wang X, Zhang Y, Peng L, Zhang H, Jiang B (December 2010). "p21-activated kinase 5 inhibits camptothecin-induced apoptosis in colorectal carcinoma cells". Tumour Biology. 31 (6): 575–82. doi:10.1007/s13277-010-0071-3. PMID 20567954. S2CID 6344093.
  35. ^ Zhang DG, Zhang J, Mao LL, Wu JX, Cao WJ, Zheng JN, Pei DS (May 2015). "p21-Activated kinase 5 affects cisplatin-induced apoptosis and proliferation in hepatocellular carcinoma cells". Tumour Biology. 36 (5): 3685–91. doi:10.1007/s13277-014-3007-5. PMID 25560489. S2CID 11752910.