Serine/threonine-protein kinase PAK 4

Details

Name
Serine/threonine-protein kinase PAK 4
Synonyms
  • 2.7.11.1
  • KIAA1142
  • p21-activated kinase 4
  • PAK-4
Gene Name
PAK4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051894|Serine/threonine-protein kinase PAK 4
MFGKRKKRVEISAPSNFEHRVHTGFDQHEQKFTGLPRQWQSLIEESARRPKPLVDPACIT
SIQPGAPKTIVRGSKGAKDGALTLLLDEFENMSVTRSNSLRRDSPPPPARARQENGMPEE
PATTARGGPGKAGSRGRFAGHSEAGGGSGDRRRAGPEKRPKSSREGSGGPQESSRDKRPL
SGPDVGTPQPAGLASGAKLAAGRPFNTYPRADTDHPSRGAQGEPHDVAPNGPSAGGLAIP
QSSSSSSRPPTRARGAPSPGVLGPHASEPQLAPPACTPAAPAVPGPPGPRSPQREPQRVS
HEQFRAALQLVVDPGDPRSYLDNFIKIGEGSTGIVCIATVRSSGKLVAVKKMDLRKQQRR
ELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIAAV
CLAVLQALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSLVGTPY
WMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPRLKNLHK
VSPSLKGFLDRLLVRDPAQRATAAELLKHPFLAKAGPPASIVPLMRQNRTR
Number of residues
591
Molecular Weight
64071.49
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / cadherin binding involved in cell-cell adhesion / protein kinase activity / protein serine/threonine kinase activity / Rac GTPase binding
Processes
actin cytoskeleton organization / activation of protein kinase activity / apoptotic process / cell cycle / cell growth / cell migration / cell proliferation / cellular response to organic cyclic compound / cytoskeleton organization / dendritic spine development / negative regulation of endothelial cell apoptotic process / positive regulation of angiogenesis / regulation of apoptotic process / regulation of MAPK cascade / regulation of mitotic cell cycle / Rho protein signal transduction / signal transduction / signal transduction by protein phosphorylation / stress-activated protein kinase signaling cascade
Components
cell-cell adherens junction / focal adhesion / Golgi apparatus
General Function
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.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051895|Serine/threonine-protein kinase PAK 4 (PAK4)
ATGTTTGGGAAGAGGAAGAAGCGGGTGGAGATCTCCGCGCCGTCCAACTTCGAGCACCGC
GTGCACACGGGCTTCGACCAGCACGAGCAGAAGTTCACGGGGCTGCCCCGCCAGTGGCAG
AGCCTGATCGAGGAGTCGGCTCGCCGGCCCAAGCCCCTCGTCGACCCCGCCTGCATCACC
TCCATCCAGCCCGGGGCCCCCAAGACCATCGTGCGGGGCAGCAAAGGTGCCAAAGATGGG
GCCCTCACGCTGCTGCTGGACGAGTTTGAGAACATGTCGGTGACACGCTCCAACTCCCTG
CGGAGAGACAGCCCGCCGCCGCCCGCCCGTGCCCGCCAGGAAAATGGGATGCCAGAGGAG
CCGGCCACCACGGCCAGAGGGGGCCCAGGGAAGGCAGGCAGCCGAGGCCGGTTCGCCGGT
CACAGCGAGGCGGGTGGCGGCAGTGGTGACAGGCGACGGGCGGGGCCAGAGAAGAGGCCC
AAGTCTTCCAGGGAGGGCTCAGGGGGTCCCCAGGAGTCCTCCCGGGACAAACGCCCCCTC
TCCGGGCCTGATGTCGGCACCCCCCAGCCTGCTGGTCTGGCCAGTGGGGCGAAACTGGCA
GCTGGCCGGCCCTTTAACACCTACCCGAGGGCTGACACGGACCACCCATCCCGGGGTGCC
CAGGGGGAGCCTCATGACGTGGCCCCTAACGGGCCATCAGCGGGGGGCCTGGCCATCCCC
CAGTCCTCCTCCTCCTCCTCCCGGCCTCCCACCCGAGCCCGAGGTGCCCCCAGCCCTGGA
GTGCTGGGACCCCACGCCTCAGAGCCCCAGCTGGCCCCTCCAGCCTGCACCCCCGCCGCC
CCTGCTGTTCCTGGGCCCCCTGGCCCCCGCTCACCACAGCGGGAGCCACAGCGAGTATCC
CATGAGCAGTTCCGGGCTGCCCTGCAGCTGGTGGTGGACCCAGGCGACCCCCGCTCCTAC
CTGGACAACTTCATCAAGATTGGCGAGGGCTCCACGGGCATCGTGTGCATCGCCACCGTG
CGCAGCTCGGGCAAGCTGGTGGCCGTCAAGAAGATGGACCTGCGCAAGCAGCAGAGGCGC
GAGCTGCTCTTCAACGAGGTGGTAATCATGAGGGACTACCAGCACGAGAATGTGGTGGAG
ATGTACAACAGCTACCTGGTGGGGGACGAGCTCTGGGTGGTCATGGAGTTCCTGGAAGGA
GGCGCCCTCACCGACATCGTCACCCACACCAGGATGAACGAGGAGCAGATCGCGGCCGTG
TGCCTTGCAGTGCTGCAGGCCCTGTCGGTGCTCCACGCCCAGGGCGTCATCCACCGGGAC
ATCAAGAGCGACTCGATCCTGCTGACCCATGATGGCAGGGTGAAGCTGTCAGACTTTGGG
TTCTGCGCCCAGGTGAGCAAGGAAGTGCCCCGAAGGAAGTCGCTGGTCGGCACGCCCTAC
TGGATGGCCCCAGAGCTCATCTCCCGCCTTCCCTACGGGCCAGAGGTAGACATCTGGTCG
CTGGGGATAATGGTGATTGAGATGGTGGACGGAGAGCCCCCCTACTTCAACGAGCCACCC
CTCAAAGCCATGAAGATGATTCGGGACAACCTGCCACCCCGACTGAAGAACCTGCACAAG
GTGTCGCCATCCCTGAAGGGCTTCCTGGACCGCCTGCTGGTGCGAGACCCTGCCCAGCGG
GCCACGGCAGCCGAGCTGCTGAAGCACCCATTCCTGGCCAAGGCAGGGCCGCCTGCCAGC
ATCGTGCCCCTCATGCGCCAGAACCGCACCAGATGA
Chromosome Location
19
Locus
19q13.2
External Identifiers
ResourceLink
UniProtKB IDO96013
UniProtKB Entry NamePAK4_HUMAN
HGNC IDHGNC:16059
General References
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  6. Gnesutta N, Qu J, Minden A: The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis. J Biol Chem. 2001 Apr 27;276(17):14414-9. Epub 2001 Jan 24. [Article]
  7. Qu J, Cammarano MS, Shi Q, Ha KC, de Lanerolle P, Minden A: Activated PAK4 regulates cell adhesion and anchorage-independent growth. Mol Cell Biol. 2001 May;21(10):3523-33. [Article]
  8. Zhang H, Li Z, Viklund EK, Stromblad S: P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration. J Cell Biol. 2002 Sep 30;158(7):1287-97. [Article]
  9. Gnesutta N, Minden A: Death receptor-induced activation of initiator caspase 8 is antagonized by serine/threonine kinase PAK4. Mol Cell Biol. 2003 Nov;23(21):7838-48. [Article]
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  12. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
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  14. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
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  28. Baskaran Y, Ang KC, Anekal PV, Chan WL, Grimes JM, Manser E, Robinson RC: An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nat Commun. 2015 Nov 26;6:8681. doi: 10.1038/ncomms9681. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails