Q64303
SS
Gene name |
Pak2 |
Protein name |
Serine/threonine-protein kinase PAK 2 |
Names |
Gamma-PAK, p21-activated kinase 2, PAK-2 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:29432 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
The p21-activated kinases (PAKs) controls cytoskeletal actin assembly and activate MAP-kinase pathways. In a study with PAK1 (Q13153), the kinase domain in the C terminus of PAK1 is inhibited by the IS domain via the C lobe, in which the kinase inhibitory segment hinders a part of the kinase domain and stabilizes a disabled catalytic site.
Autoinhibitory domains (AIDs)
Target domain |
249-500 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
385-408 (Activation loop from InterPro)
Target domain |
229-524 (Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2) |
Relief mechanism |
|
Assay |
|
References
- Lei M et al. (2000) "Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch", Cell, 102, 387-97
- Totaro A et al. (2007) "Identification of an intramolecular interaction important for the regulation of GIT1 functions", Molecular biology of the cell, 18, 5124-38
- Bautista L et al. (2020) "p21-Activated Kinases in Thyroid Cancer", Endocrinology, 161,
- Chong C et al. (2001) "The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity", The Journal of biological chemistry, 276, 17347-53
- Wang J et al. (2011) "Structural insights into the autoactivation mechanism of p21-activated protein kinase", Structure (London, England : 1993), 19, 1752-61
- Ha BH et al. (2012) "Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate", Proceedings of the National Academy of Sciences of the United States of America, 109, 16107-12
- Rousseau V et al. (2003) "A new constitutively active brain PAK3 isoform displays modified specificities toward Rac and Cdc42 GTPases", The Journal of biological chemistry, 278, 3912-20
- Ching YP et al. (2003) "Identification of an autoinhibitory domain of p21-activated protein kinase 5", The Journal of biological chemistry, 278, 33621-4
- Dan C et al. (2002) "PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells", Molecular and cellular biology, 22, 567-77
- Kaur R et al. (2005) "Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase", The Journal of biological chemistry, 280, 3323-30
- Gao J et al. (2013) "Substrate and inhibitor specificity of the type II p21-activated kinase, PAK6", PloS one, 8, e77818
Autoinhibited structure
Activated structure
2 structures for Q64303
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2DF6 | X-ray | 130 A | C/D | 180-197 | PDB |
| AF-Q64303-F1 | Predicted | AlphaFoldDB |
1 variants for Q64303
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs197622643 | 167 | V>M | No | Ensembl |
No associated diseases with Q64303
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
9 GO annotations of cellular component
| Name | Definition |
|---|---|
| cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
| postsynaptic density | An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
| secretory granule | A small subcellular vesicle, surrounded by a membrane, that is formed from the Golgi apparatus and contains a highly concentrated protein destined for secretion. Secretory granules move towards the periphery of the cell and upon stimulation, their membranes fuse with the cell membrane, and their protein load is exteriorized. Processing of the contained protein may take place in secretory granules. |
9 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| identical protein binding | Binding to an identical protein or proteins. |
| protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| protein serine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. |
| protein serine/threonine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. |
| protein serine/threonine/tyrosine kinase activity | Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
| protein tyrosine kinase activator activity | Increases the activity of a protein tyrosine kinase, an enzyme which phosphorylates a tyrosyl phenolic group on a protein. |
| small GTPase binding | Binding to a small monomeric GTPase. |
20 GO annotations of biological process
| Name | Definition |
|---|---|
| adherens junction assembly | The aggregation, arrangement and bonding together of a set of components to form an adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments. |
| bicellular tight junction assembly | The aggregation, arrangement and bonding together of a set of components to form a tight junction, an occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet. |
| cardiac muscle hypertrophy | The enlargement or overgrowth of all or part of the heart muscle due to an increase in size of cardiac muscle cells without cell division. |
| cellular response to organic cyclic compound | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. |
| cellular response to transforming growth factor beta stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus. |
| dendritic spine development | The process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| negative regulation of apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. |
| negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis | Any process that stops, prevents or reduces the frequency, rate or extent of cysteine-type endopeptidase activity involved in execution phase of apoptosis. |
| negative regulation of stress fiber assembly | Any process that stops, prevents, or reduces the frequency, rate or extent of the assembly a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. |
| peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| positive regulation of extrinsic apoptotic signaling pathway | Any process that activates or increases the frequency, rate or extent of extrinsic apoptotic signaling pathway. |
| positive regulation of peptidyl-tyrosine phosphorylation | Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. |
| protein autophosphorylation | The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation). |
| protein localization to cell-cell junction | A process in which a protein is transported to, or maintained, in a location within a cell-cell junction. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of axonogenesis | Any process that modulates the frequency, rate or extent of axonogenesis, the generation of an axon, the long process of a neuron. |
| regulation of cytoskeleton organization | Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures. |
| regulation of MAPK cascade | Any process that modulates the frequency, rate or extent of signal transduction mediated by the MAP kinase (MAPK) cascade. |
23 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q12469 | SKM1 | Serine/threonine-protein kinase SKM1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q08E52 | PAK1 | Serine/threonine-protein kinase PAK 1 | Bos taurus (Bovine) | SS |
| Q7YQL4 | PAK3 | Serine/threonine-protein kinase PAK 3 | Pan troglodytes (Chimpanzee) | SS |
| Q9VXE5 | mbt | Serine/threonine-protein kinase PAK mbt | Drosophila melanogaster (Fruit fly) | PR |
| Q9P286 | PAK5 | Serine/threonine-protein kinase PAK 5 | Homo sapiens (Human) | EV |
| Q9NQU5 | PAK6 | Serine/threonine-protein kinase PAK 6 | Homo sapiens (Human) | EV |
| O96013 | PAK4 | Serine/threonine-protein kinase PAK 4 | Homo sapiens (Human) | EV |
| O75914 | PAK3 | Serine/threonine-protein kinase PAK 3 | Homo sapiens (Human) | SS |
| Q13153 | PAK1 | Serine/threonine-protein kinase PAK 1 | Homo sapiens (Human) | EV |
| Q13177 | PAK2 | Serine/threonine-protein kinase PAK 2 | Homo sapiens (Human) | EV |
| O88643 | Pak1 | Serine/threonine-protein kinase PAK 1 | Mus musculus (Mouse) | SS |
| Q8C015 | Pak5 | Serine/threonine-protein kinase PAK 5 | Mus musculus (Mouse) | SS |
| Q3ULB5 | Pak6 | Serine/threonine-protein kinase PAK 6 | Mus musculus (Mouse) | PR |
| Q61036 | Pak3 | Serine/threonine-protein kinase PAK 3 | Mus musculus (Mouse) | SS |
| Q8CIN4 | Pak2 | Serine/threonine-protein kinase PAK 2 | Mus musculus (Mouse) | SS |
| Q64303 | Pak2 | Serine/threonine-protein kinase PAK 2 | Rattus norvegicus (Rat) | SS |
| D4A280 | Pak5 | Serine/threonine-protein kinase PAK 5 | Rattus norvegicus (Rat) | SS |
| P35465 | Pak1 | Serine/threonine-protein kinase PAK 1 | Rattus norvegicus (Rat) | SS |
| Q62829 | Pak3 | Serine/threonine-protein kinase PAK 3 | Rattus norvegicus (Rat) | SS |
| O54748 | Stk3 | Serine/threonine-protein kinase 3 | Rattus norvegicus (Rat) | SS |
| G5EFU0 | pak-2 | Serine/threonine-protein kinase pak-2 | Caenorhabditis elegans | PR |
| Q17850 | pak-1 | Serine/threonine-protein kinase pak-1 | Caenorhabditis elegans | PR |
| G5EGQ3 | max-2 | Serine/threonine-protein kinase max-2 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSDNGELEDK | PPAPPVRMSS | TIFSTGGKDP | LSANHSLKPL | PSVPEEKKPR | NKIISIFSST |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EKGSKKKEKE | RPEISPPSDF | EHTIHVGFDA | VTGEFTGMPE | QWARLLQTSN | ITKLEQKKNP |
| 130 | 140 | 150 | 160 | 170 | 180 |
| QAVLDVLKFY | DSNTVKQKYL | SFTPPEKDGF | PSGTPALNTK | GSETSAVVTE | EDDDDEDAAP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PVIAPRPDHT | KSIYTRSVID | PIPAPVGDSN | VDSGAKSSDK | QKKKAKMTDE | EIMEKLRTIV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SIGDPKKKYT | RYEKIGQGAS | GTVFTATDVA | LGQEVAIKQI | NLQKQPKKEL | IINEILVMKE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LKNPNIVNFL | DSYLVGDELF | VVMEYLAGGS | LTDVVTETCM | DEAQIAAVCR | ECLQALEFLH |
| 370 | 380 | 390 | 400 | 410 | 420 |
| ANQVIHRDIK | SDNVLLGMEG | SVKLTDFGFC | AQITPEQSKR | STMVGTPYWM | APEVVTRKAY |
| 430 | 440 | 450 | 460 | 470 | 480 |
| GPKVDIWSLG | IMAIEMVEGE | PPYLNENPLR | ALYLIATNGT | PELQNPEKLS | PIFRDFLNRC |
| 490 | 500 | 510 | 520 | ||
| LEMDVEKRGS | AKELLQHPFL | KLAKPLSSLT | PLILAAKEAM | KSNR |