Q61036
SS
Gene name |
Pak3 (Pak-3, Pakb, Stk4) |
Protein name |
Serine/threonine-protein kinase PAK 3 |
Names |
Beta-PAK, CDC42/RAC effector kinase PAK-B, p21-activated kinase 3, PAK-3 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:18481 |
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 |
283-534 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
419-442 (Activation loop from InterPro)
Target domain |
283-534 (Protein kinase domain) |
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 Q61036
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1EES | NMR | - | B | 63-123 | PDB |
| AF-Q61036-F1 | Predicted | AlphaFoldDB |
2 variants for Q61036
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs261170575 | 225 | I>V | No | Ensembl | |
| rs220461768 | 236 | I>T | No | Ensembl |
No associated diseases with Q61036
5 regional properties for Q61036
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | CRIB domain | 69 - 141 | IPR000095 |
| domain | Protein kinase domain | 283 - 534 | IPR000719 |
| active_site | Serine/threonine-protein kinase, active site | 398 - 410 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 289 - 312 | IPR017441 |
| domain | p21 activated kinase binding domain | 68 - 128 | IPR033923 |
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 | |
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| 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. |
9 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| GTPase binding | Binding to a GTPase, any enzyme that catalyzes the hydrolysis of GTP. |
| MAP kinase kinase activity | Catalysis of the concomitant phosphorylation of threonine (T) and tyrosine (Y) residues in a Thr-Glu-Tyr (TEY) thiolester sequence in a MAP kinase (MAPK) substrate. |
| metal ion binding | Binding to a metal ion. |
| 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 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. |
| SH3 domain binding | Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins. |
| small GTPase binding | Binding to a small monomeric GTPase. |
16 GO annotations of biological process
| Name | Definition |
|---|---|
| axonogenesis | De novo generation of a long process of a neuron, including the terminal branched region. Refers to the morphogenesis or creation of shape or form of the developing axon, which carries efferent (outgoing) action potentials from the cell body towards target cells. |
| 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. |
| dendrite development | The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure. |
| 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. |
| dendritic spine morphogenesis | The process in which the anatomical structures of a dendritic spine are generated and organized. 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. |
| positive regulation of dendritic spine morphogenesis | Any process that increases the rate, frequency, or extent of dendritic spine morphogenesis, the process in which the anatomical structures of a dendritic spine are generated and organized. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission. |
| positive regulation of DNA biosynthetic process | Any process that activates or increases the frequency, rate or extent of DNA biosynthetic process. |
| positive regulation of fibroblast migration | Any process that increases the rate, frequency or extent of fibroblast cell migration. Fibroblast cell migration is accomplished by extension and retraction of a pseudopodium. |
| positive regulation of neuron apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of actin cytoskeleton organization | Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| regulation of actin filament polymerization | Any process that modulates the frequency, rate or extent of the assembly of actin filaments by the addition of actin monomers to a filament. |
| 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 MAPK cascade | Any process that modulates the frequency, rate or extent of signal transduction mediated by the MAP kinase (MAPK) cascade. |
| regulation of neuron projection development | Any process that modulates the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). |
27 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 |
| Q13153 | PAK1 | Serine/threonine-protein kinase PAK 1 | Homo sapiens (Human) | EV |
| Q13177 | PAK2 | Serine/threonine-protein kinase PAK 2 | Homo sapiens (Human) | EV |
| O75914 | PAK3 | Serine/threonine-protein kinase PAK 3 | Homo sapiens (Human) | SS |
| Q9JI11 | Stk4 | Serine/threonine-protein kinase 4 | Mus musculus (Mouse) | PR |
| Q9JI10 | Stk3 | Serine/threonine-protein kinase 3 | Mus musculus (Mouse) | SS |
| Q3ULB5 | Pak6 | Serine/threonine-protein kinase PAK 6 | Mus musculus (Mouse) | PR |
| Q8C015 | Pak5 | Serine/threonine-protein kinase PAK 5 | Mus musculus (Mouse) | SS |
| Q8BTW9 | Pak4 | Serine/threonine-protein kinase PAK 4 | Mus musculus (Mouse) | PR |
| Q8CIN4 | Pak2 | Serine/threonine-protein kinase PAK 2 | Mus musculus (Mouse) | SS |
| Q9JM52 | Mink1 | Misshapen-like kinase 1 | Mus musculus (Mouse) | PR |
| P83510 | Tnik | Traf2 and NCK-interacting protein kinase | Mus musculus (Mouse) | PR |
| P97820 | Map4k4 | Mitogen-activated protein kinase kinase kinase kinase 4 | Mus musculus (Mouse) | PR |
| O88643 | Pak1 | Serine/threonine-protein kinase PAK 1 | Mus musculus (Mouse) | 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 |
| Q64303 | Pak2 | Serine/threonine-protein kinase PAK 2 | Rattus norvegicus (Rat) | SS |
| Q62829 | Pak3 | Serine/threonine-protein kinase PAK 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 |
| MSDSLDNEEK | PPAPPLRMNS | NNRDSSALNH | SSKPLPMAPE | EKNKKARLRS | IFPGGGDKTN |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KKKEKERPEI | SLPSDFEHTI | HVGFDAVTGE | FTPDLYGSQM | CPGKLPEGIP | EQWARLLQTS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| NITKLEQKKN | PQAVLDVLKF | YDSKETVNNQ | KYMSFTSGDK | SAHGYIAAHQ | SNTKTASEPP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LAPPVSEEED | EEEEEEEDDN | EPPPVIAPRP | EHTKSIYTRS | VVESIASPAA | PNKEDIPPSA |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ENANSTTLYR | NTDRQRKKSK | MTDEEILEKL | RSIVSVGDPK | KKYTRFEKIG | QGASGTVYTA |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LDIATGQEVA | IKQMNLQQQP | KKELIINEIL | VMRENKNPNI | VNYLDSYLVG | DELWVVMEYL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| AGGSLTDVVT | ETCMDEGQIA | AVCRECLQAL | DFLHSNQVIH | RDIKSDNILL | GMDGSVKLTD |
| 430 | 440 | 450 | 460 | 470 | 480 |
| FGFCAQITPE | QSKRSTMVGT | PYWMAPEVVT | RKAYGPKVDI | WSLGIMAIEM | VEGEPPYLNE |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NPLRALYLIA | TNGTPELQNP | ERLSAVFRDF | LNRCLEMDVD | RRGSAKELLQ | HPFLKLAKPL |
| 550 | |||||
| SSLTPLIIAA | KEAIKNSSR |