Q08E52

SS
Gene name
PAK1
Protein name
Serine/threonine-protein kinase PAK 1
Names
Alpha-PAK, p21-activated kinase 1, PAK-1, p65-PAK
Species
Bos taurus (Bovine)
KEGG Pathway
bta:533729
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)

83-149 (inhibitory segment) SS

Target domain

269-520 (Protein kinase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

405-428 (Activation loop from InterPro)

Target domain

269-520 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q08E52

Entry ID Method Resolution Chain Position Source
AF-Q08E52-F1 Predicted AlphaFoldDB

50 variants for Q08E52

Variant ID(s) Position Change Description Diseaes Association Provenance
rs464663376 2 S>P No Ensembl
rs434784910 8 I>L No Ensembl
rs446780180 10 D>V No Ensembl
rs468555032 14 A>S No Ensembl
rs435675974 19 N>T No Ensembl
rs476449025 33 T>N No Ensembl
rs436951522 34 L>P No Ensembl
rs470867353 38 S>T No Ensembl
rs440869923 40 P>S No Ensembl
rs474739659 55 Y>F No Ensembl
rs441713823 58 I>F No Ensembl
rs463367017 58 I>N No Ensembl
rs458306449 59 L>F No Ensembl
rs479917392 61 G>E No Ensembl
rs435534083 62 D>E No Ensembl
rs446843277 62 D>N No Ensembl
rs468418229 62 D>V No Ensembl
rs470540309 100 P>Q No Ensembl
rs440945273 111 N>T No Ensembl
rs459351052 135 K>T No Ensembl
rs481681895 140 Q>* No Ensembl
rs444184903 160 N>D No Ensembl
rs462710534 160 N>T No Ensembl
rs800484308 171 P>S No Ensembl
rs471506498 185 P>Q No Ensembl
rs446120180 233 A>S No Ensembl
rs381763110 236 R>W No Ensembl
rs448524116 279 A>V No Ensembl
rs470085042 282 T>P No Ensembl
rs465126576 283 V>A No Ensembl
rs456256881 283 V>M No Ensembl
rs432274731 284 Y>* No Ensembl
rs453970222 285 T>P No Ensembl
rs472203003 286 A>S No Ensembl
rs435954308 288 D>E No Ensembl
rs454671896 289 V>L No Ensembl
rs443274900 290 A>P No Ensembl
rs459086764 291 T>P No Ensembl
rs441510070 293 Q>K No Ensembl
rs459859364 293 Q>R No Ensembl
rs448386707 294 E>G No Ensembl
rs481246670 294 E>Q No Ensembl
rs460217536 327 V>L No Ensembl
rs518227183 367 A>S No Ensembl
rs458690512 520 L>R No Ensembl
rs477320047 524 K>M No Ensembl
rs447454650 524 K>N No Ensembl
rs459382671 525 P>S No Ensembl
rs478535217 531 P>L No Ensembl
rs481057682 542 N>S No Ensembl

No associated diseases with Q08E52

6 regional properties for Q08E52

Type Name Position InterPro Accession
domain C2 domain 707 - 835 IPR000008
domain Phosphatidylinositol-specific phospholipase C, X domain 317 - 469 IPR000909
domain Phospholipase C, phosphatidylinositol-specific, Y domain 590 - 706 IPR001711
domain Phospholipase C-beta, C-terminal domain 1029 - 1200 IPR014815
domain Phosphoinositide-specific phospholipase C, EF-hand-like domain 217 - 308 IPR015359
domain PLC-beta, PH domain 18 - 149 IPR037862

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Cell junction, focal adhesion
  • Cell projection, lamellipodium
  • Cell membrane
  • Cell projection, ruffle membrane
  • Cell projection, invadopodium
  • Nucleus, nucleoplasm
  • Chromosome
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Recruited to the cell membrane by interaction with CDC42 and RAC1
  • Recruited to focal adhesions upon activation
  • Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin
  • Colocalizes with RUFY3, F-actin and other core migration components in invadopodia at the cell periphery (By similarity)
  • Upon DNA damage, translocates to the nucleoplasm when phosphorylated at Thr-212 where is co-recruited with MORC2 on damaged chromatin (By similarity)
  • Localization to the centrosome does not depend upon the presence of gamma-tubulin (By similarity)
  • Localization of the active, but not inactive, protein to the adhesions and edge of lamellipodia is mediated by interaction with GIT1 (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

13 GO annotations of cellular component

Name Definition
actin filament A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane.
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.
chromosome A structure composed of a very long molecule of DNA and associated proteins (e.g. histones) that carries hereditary information.
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.
focal adhesion A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
lamellipodium A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments.
microtubule organizing center An intracellular structure that can catalyze gamma-tubulin-dependent microtubule nucleation and that can anchor microtubules by interacting with their minus ends, plus ends or sides.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.
ruffle membrane The portion of the plasma membrane surrounding a ruffle.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
collagen binding Binding to collagen, a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. Collagen is highly enriched in glycine (some regions are 33% glycine) and proline, occurring predominantly as 3-hydroxyproline (about 20%).
gamma-tubulin binding Binding to the microtubule constituent protein gamma-tubulin.
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.
small GTPase binding Binding to a small monomeric GTPase.

25 GO annotations of biological process

Name Definition
actin cytoskeleton reorganization A process that is carried out at the cellular level which results in dynamic structural changes to the arrangement of constituent parts of cytoskeletal structures comprising actin filaments and their associated proteins.
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
branching morphogenesis of an epithelial tube The process in which the anatomical structures of branches in an epithelial tube are generated and organized. A tube is a long hollow cylinder.
cell migration The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
cellular response to DNA damage 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 stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
chromatin remodeling A dynamic process of chromatin reorganization resulting in changes to chromatin structure. These changes allow DNA metabolic processes such as transcriptional regulation, DNA recombination, DNA repair, and DNA replication.
exocytosis A process of secretion by a cell that results in the release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle. Exocytosis can occur either by full fusion, when the vesicle collapses into the plasma membrane, or by a kiss-and-run mechanism that involves the formation of a transient contact, a pore, between a granule (for exemple of chromaffin cells) and the plasma membrane. The latter process most of the time leads to only partial secretion of the granule content. Exocytosis begins with steps that prepare vesicles for fusion with the membrane (tethering and docking) and ends when molecules are secreted from the cell.
hepatocyte growth factor receptor signaling pathway The series of molecular signals initiated by a ligand binding to a hepatocyte growth factor receptor, and ending with the regulation of a downstream cellular process, e.g. transcription.
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 cell proliferation involved in contact inhibition Any process that stops, prevents or reduces the rate or extent of cell proliferation in response to cell density.
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 cell migration Any process that activates or increases the frequency, rate or extent of cell migration.
positive regulation of cell population proliferation Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of intracellular estrogen receptor signaling pathway Any process that activates or increases the frequency, rate or extent of the activity of an intracellular estrogen receptor signaling pathway.
positive regulation of JUN kinase activity Any process that activates or increases the frequency, rate or extent of JUN kinase activity.
positive regulation of microtubule nucleation Any process that increases the rate, frequency or extent of microtubule nucleation. Microtubule nucleation is the 'de novo' formation of a microtubule, in which tubulin heterodimers form metastable oligomeric aggregates, some of which go on to support formation of a complete microtubule. Microtubule nucleation usually occurs from a specific site within a cell.
positive regulation of peptidyl-serine phosphorylation Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of stress fiber assembly Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts.
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 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 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.
wound healing The series of events that restore integrity to a damaged tissue, following an injury.

22 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
Q5E9L6 STK4 Serine/threonine-protein kinase 4 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
Q13177 PAK2 Serine/threonine-protein kinase PAK 2 Homo sapiens (Human) EV
Q13153 PAK1 Serine/threonine-protein kinase PAK 1 Homo sapiens (Human) EV
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
O88643 Pak1 Serine/threonine-protein kinase PAK 1 Mus musculus (Mouse) SS
Q62829 Pak3 Serine/threonine-protein kinase PAK 3 Rattus norvegicus (Rat) SS
D4A280 Pak5 Serine/threonine-protein kinase PAK 5 Rattus norvegicus (Rat) SS
Q64303 Pak2 Serine/threonine-protein kinase PAK 2 Rattus norvegicus (Rat) SS
P35465 Pak1 Serine/threonine-protein kinase PAK 1 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
MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK KDRFYRAILP
70 80 90 100 110 120
GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN
130 140 150 160 170 180
PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA EDYNSSNTLN VKAVSETPAV PPVSEDEDDD
190 200 210 220 230 240
DDGTPPPVIA PRPEHTKSVY TRSVIEPLPI TPTRDVATSP ISPTENNTTP PDALTRNTEK
250 260 270 280 290 300
QKKKPKMSDE EILEKLRSIV SVGDPKKKYT RFEKIGQGAS GTVYTAMDVA TGQEVAIKQM
310 320 330 340 350 360
NLQQQPKKEL IINEILVMRE NKNPNIVNYL DSYLVGDELW VVMEYLAGGS LTDVVTETCM
370 380 390 400 410 420
DEGQIAAVCR ECLQALEFLH SNQVIHRDIK SDNILLGMDG SVKLTDFGFC AQITPEQSKR
430 440 450 460 470 480
STMVGTPYWM APEVVTRKAY GPKVDIWSLG IMAIEMIEGE PPYLNENPLR ALYLIATNGT
490 500 510 520 530 540
PELQNPEKLS AIFRDFLNRC LEMDVEKRGS AKELLQHQFL KIAKPLSSLT PLIAAAKEAT
KNNH