Serine/threonine-protein kinase PAK 3

Details

Name
Serine/threonine-protein kinase PAK 3
Synonyms
  • 2.7.11.1
  • Beta-PAK
  • Oligophrenin-3
  • OPHN3
  • p21-activated kinase 3
  • PAK-3
Gene Name
PAK3
UniProtKB Entry
O75914Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0051892|Serine/threonine-protein kinase PAK 3
MSDGLDNEEKPPAPPLRMNSNNRDSSALNHSSKPLPMAPEEKNKKARLRSIFPGGGDKTN
KKKEKERPEISLPSDFEHTIHVGFDAVTGEFTPDLYGSQMCPGKLPEGIPEQWARLLQTS
NITKLEQKKNPQAVLDVLKFYDSKETVNNQKYMSFTSGDKSAHGYIAAHPSSTKTASEPP
LAPPVSEEEDEEEEEEEDENEPPPVIAPRPEHTKSIYTRSVVESIASPAVPNKEVTPPSA
ENANSSTLYRNTDRQRKKSKMTDEEILEKLRSIVSVGDPKKKYTRFEKIGQGASGTVYTA
LDIATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYL
AGGSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTD
FGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNE
NPLRALYLIATNGTPELQNPERLSAVFRDFLNRCLEMDVDRRGSAKELLQHPFLKLAKPL
SSLTPLIIAAKEAIKNSSR
Number of residues
559
Molecular Weight
62309.08
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / MAP kinase kinase activity / metal ion binding / protein serine/threonine kinase activity / SH3 domain binding
Processes
axonogenesis / cellular response to organic cyclic compound / dendrite development / dendritic spine morphogenesis / ephrin receptor signaling pathway / regulation of actin filament polymerization / regulation of axonogenesis / stimulatory C-type lectin receptor signaling pathway / synapse organization
Components
cytoplasm / cytosol / plasma membrane
General Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as a downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051893|Serine/threonine-protein kinase PAK 3 (PAK3)
ATGTCTGACGGTCTGGATAATGAAGAGAAACCCCCGGCTCCTCCACTGAGGATGAATAGT
AACAACCGGGATTCTTCAGCACTCAACCACAGCTCCAAACCACTTCCCATGGCCCCTGAA
GAGAAGAATAAGAAAGCCAGGCTTCGCTCTATCTTCCCAGGAGGAGGGGATAAAACCAAT
AAGAAGAAGGAGAAAGAGCGCCCAGAGATCTCTCTTCCTTCAGACTTTGAGCATACGATT
CATGTGGGGTTTGATGCAGTCACCGGGGAATTCACTCCAGATCTCTATGGCTCACAGATG
TGCCCAGGGAAGCTCCCAGAGGGAATTCCAGAGCAATGGGCACGATTACTCCAAACTTCC
AACATAACAAAATTGGAACAGAAGAAGAACCCACAAGCTGTTCTAGATGTTCTCAAATTC
TATGATTCCAAAGAAACAGTCAACAACCAGAAATACATGAGCTTTACATCAGGAGATAAA
AGTGCACATGGATACATAGCAGCCCATCCTTCGAGTACAAAAACAGCATCTGAGCCTCCA
TTGGCCCCTCCTGTGTCTGAAGAAGAAGATGAAGAGGAAGAAGAAGAAGAAGATGAAAAT
GAGCCACCACCAGTTATCGCACCAAGACCAGAGCATACAAAATCAATCTATACTCGTTCT
GTGGTTGAATCCATTGCTTCACCAGCAGTACCAAATAAAGAGGTCACACCACCCTCTGCT
GAAAATGCCAATTCCAGTACTTTGTACAGGAACACAGATCGGCAAAGAAAAAAATCCAAG
ATGACAGATGAGGAGATCTTAGAGAAGCTAAGAAGCATTGTGAGTGTTGGGGACCCAAAG
AAAAAATACACAAGATTTGAAAAAATTGGTCAAGGGGCATCAGGTACTGTTTATACAGCA
CTAGACATTGCAACAGGACAAGAGGTGGCCATAAAGCAGATGAACCTTCAACAGCAACCC
AAGAAGGAATTAATTATTAATGAAATTCTGGTCATGAGGGAAAATAAGAACCCTAATATT
GTTAATTATTTAGATAGCTACTTGGTGGGTGATGAACTATGGGTAGTCATGGAATACTTG
GCTGGTGGCTCTCTGACTGATGTGGTCACAGAGACCTGTATGGATGAAGGACAGATAGCA
GCTGTCTGCAGAGAGTGCCTGCAAGCTTTGGATTTCCTGCACTCAAACCAGGTGATCCAT
AGAGATATAAAGAGTGACAATATTCTTCTCGGGATGGATGGCTCTGTTAAATTGACTGAC
TTTGGGTTCTGTGCCCAGATCACTCCTGAGCAAAGTAAACGAAGCACTATGGTGGGAACC
CCATATTGGATGGCACCTGAGGTGGTGACTCGAAAAGCTTATGGTCCGAAAGTTGATATC
TGGTCTCTTGGAATTATGGCAATTGAAATGGTGGAAGGTGAACCCCCTTACCTTAATGAA
AATCCACTCAGGGCATTGTATCTGATAGCCACTAATGGAACTCCAGAGCTCCAGAATCCT
GAGAGACTGTCAGCTGTATTCCGTGACTTTTTAAATCGCTGTCTTGAGATGGATGTGGAT
AGGCGAGGATCTGCCAAGGAGCTTTTGCAGCATCCATTTTTAAAATTAGCCAAGCCTCTC
TCCAGCCTGACTCCTCTGATTATCGCTGCAAAGGAAGCAATTAAGAACAGCAGCCGCTAA
Chromosome Location
X
Locus
Xq23
External Identifiers
ResourceLink
UniProtKB IDO75914
UniProtKB Entry NamePAK3_HUMAN
GeneCard IDPAK3
HGNC IDHGNC:8592
PDB ID(s)6FD3
KEGG IDhsa:5063
IUPHAR/Guide To Pharmacology ID2135
NCBI Gene ID5063
General References
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  2. Kitano T, Schwarz C, Nickel B, Paabo S: Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees. Mol Biol Evol. 2003 Aug;20(8):1281-9. Epub 2003 May 30. [Article]
  3. Kreis P, Rousseau V, Thevenot E, Combeau G, Barnier JV: The four mammalian splice variants encoded by the p21-activated kinase 3 gene have different biological properties. J Neurochem. 2008 Aug;106(3):1184-97. doi: 10.1111/j.1471-4159.2008.05474.x. Epub 2008 May 27. [Article]
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  6. Chong C, Tan L, Lim L, Manser E: The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity. J Biol Chem. 2001 May 18;276(20):17347-53. Epub 2001 Feb 22. [Article]
  7. Feng Q, Albeck JG, Cerione RA, Yang W: Regulation of the Cool/Pix proteins: key binding partners of the Cdc42/Rac targets, the p21-activated kinases. J Biol Chem. 2002 Feb 15;277(7):5644-50. Epub 2001 Dec 10. [Article]
  8. McPhie DL, Coopersmith R, Hines-Peralta A, Chen Y, Ivins KJ, Manly SP, Kozlowski MR, Neve KA, Neve RL: DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. J Neurosci. 2003 Jul 30;23(17):6914-27. [Article]
  9. Del Rincon SV, Rogers J, Widschwendter M, Sun D, Sieburg HB, Spruck C: Development and validation of a method for profiling post-translational modification activities using protein microarrays. PLoS One. 2010 Jun 28;5(6):e11332. doi: 10.1371/journal.pone.0011332. [Article]
  10. Deleris P, Trost M, Topisirovic I, Tanguay PL, Borden KL, Thibault P, Meloche S: Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway. J Biol Chem. 2011 Feb 25;286(8):6470-8. doi: 10.1074/jbc.M110.181529. Epub 2010 Dec 22. [Article]
  11. Kreis P, Barnier JV: PAK signalling in neuronal physiology. Cell Signal. 2009 Mar;21(3):384-93. doi: 10.1016/j.cellsig.2008.11.001. Epub 2008 Nov 12. [Article]
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  13. Gedeon AK, Nelson J, Gecz J, Mulley JC: X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3. Am J Med Genet A. 2003 Aug 1;120A(4):509-17. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Serine/threonine-protein kinase PAK 3 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Fostamatinibapproved, investigationalunknowntargetinhibitorDetails