Search Results

Overview

Uniprot IDP35465
Protein NameSerine/threonine-protein kinase PAK 1
Gene NamePak1
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
266 IVSVGDPKKKYTRFE
63 RSILAGDKTNKKKEK

Function

Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:12876277, PubMed:14707132, PubMed:19029984, PubMed:9032240, PubMed:9528787). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (PubMed:12876277, PubMed:19029984, PubMed:9032240, PubMed:9528787). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9774440). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (By similarity). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (By similarity). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (By similarity). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (By similarity). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (By similarity). In podocytes, promotes NR3C2 nuclear localization (PubMed:19029984). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (By similarity). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (PubMed:24089484). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (By similarity). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (By similarity). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (PubMed:25284783). 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). Along with GIT1, positively regulates microtubule nucleation during interphase (By similarity). Phosphorylates FXR1, promoting its localization to stress granules and activity (By similarity). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (By similarity)

Protein Sequence

10 MSNNGLDVQD 20 KPPAPPMRNT 30 STMIGAGSKD 40 PGTLNHGSKP 50 LPPNPEEKKK 60 KDRFYRSILA 70 GDKTNKKKEK 80 ERPEISLPSD 90 FEHTIHVGFD 100 AVTGEFTGMP 110 EQWARLLQTS 120 NITKSEQKKN 130 PQAVLDVLEF 140 YNSKKTSNSQ 150 KYMSFTDKSA 160 EDYNSSNTLN 170 VKTVSETPAV 180 PPVSEDEDDD 190 DDATPPPVIA 200 PRPEHTKSVY 210 TRSVIEPLPV 220 TPTRDVATSP 230 ISPTENNTTP 240 PDALTRNTEK 250 QKKKPKMSDE 260 EILEKLRSIV 270 SVGDPKKKYT 280 RFEKIGQGAS 290 GTVYTAMDVA 300 TGQEVAIKQM 310 NLQQQPKKEL 320 IINEILVMRE 330 NKNPNIVNYL 340 DSYLVGDELW 350 VVMEYLAGGS 360 LTDVVTETCM 370 DEGQIAAVCR 380 ECLQALEFLH 390 SNQVIHRDIK 400 SDNILLGMDG 410 SVKLTDFGFC 420 AQITPEQSKR 430 STMVGTPYWM 440 APEVVTRKAY 450 GPKVDIWSLG 460 IMAIEMIEGE 470 PPYLNENPLR 480 ALYLIATNGT 490 PELQNPEKLS 500 AIFRDFLNRC 510 LEMDVEKRGS 520 AKELLQHQFL 530 KIAKPLSSLT 540 PLIAAAKEAT KNNH

Gene Ontology

Classification GO ID Description
Biological Process GO:0006468 protein phosphorylation
Cellular Component GO:0005884 actin filament
Cellular Component GO:0030424 axon
Cellular Component GO:0005911 cell-cell junction
Cellular Component GO:0005813 centrosome
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0030425 dendrite
Cellular Component GO:0005925 focal adhesion
Cellular Component GO:0098982 GABA-ergic synapse
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0030426 growth cone
Cellular Component GO:0014704 intercalated disc
Cellular Component GO:0030027 lamellipodium
Cellular Component GO:0031965 nuclear membrane
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0014069 postsynaptic density
Cellular Component GO:0098793 presynapse
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0001726 ruffle
Cellular Component GO:0032587 ruffle membrane
Cellular Component GO:0030018 Z disc
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0005518 collagen binding
Molecular Function GO:0043015 gamma-tubulin binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0004709 MAP kinase kinase kinase activity
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0031267 small GTPase binding
Biological Process GO:0030036 actin cytoskeleton organization
Biological Process GO:0021764 amygdala development
Biological Process GO:0006915 apoptotic process
Biological Process GO:0048754 branching morphogenesis of an epithelial tube
Biological Process GO:0016477 cell migration
Biological Process GO:0032869 cellular response to insulin stimulus
Biological Process GO:0009267 cellular response to starvation
Biological Process GO:0021549 cerebellum development
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0016358 dendrite development
Biological Process GO:0060996 dendritic spine development
Biological Process GO:0006974 DNA damage response
Biological Process GO:0030010 establishment of cell polarity
Biological Process GO:0006887 exocytosis
Biological Process GO:0061534 gamma-aminobutyric acid secretion, neurotransmission
Biological Process GO:0061535 glutamate secretion, neurotransmission
Biological Process GO:0048012 hepatocyte growth factor receptor signaling pathway
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
Biological Process GO:0060244 negative regulation of cell proliferation involved in contact inhibition
Biological Process GO:0007528 neuromuscular junction development
Biological Process GO:0048812 neuron projection morphogenesis
Biological Process GO:0098597 observational learning
Biological Process GO:0045773 positive regulation of axon extension
Biological Process GO:0030335 positive regulation of cell migration
Biological Process GO:0008284 positive regulation of cell population proliferation
Biological Process GO:0010763 positive regulation of fibroblast migration
Biological Process GO:0046628 positive regulation of insulin receptor signaling pathway
Biological Process GO:0033148 positive regulation of intracellular estrogen receptor signaling pathway
Biological Process GO:0090063 positive regulation of microtubule nucleation
Biological Process GO:0033138 positive regulation of peptidyl-serine phosphorylation
Biological Process GO:0090314 positive regulation of protein targeting to membrane
Biological Process GO:0051496 positive regulation of stress fiber assembly
Biological Process GO:1904754 positive regulation of vascular associated smooth muscle cell migration
Biological Process GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
Biological Process GO:0046777 protein autophosphorylation
Biological Process GO:1903608 protein localization to cytoplasmic stress granule
Biological Process GO:0043113 receptor clustering
Biological Process GO:0032956 regulation of actin cytoskeleton organization
Biological Process GO:0050770 regulation of axonogenesis
Biological Process GO:0010468 regulation of gene expression
Biological Process GO:1900271 regulation of long-term synaptic potentiation
Biological Process GO:0043408 regulation of MAPK cascade
Biological Process GO:0150036 regulation of trans-synaptic signaling by endocannabinoid, modulating synaptic transmission
Biological Process GO:0001666 response to hypoxia
Biological Process GO:0007264 small GTPase-mediated signal transduction
Biological Process GO:0019226 transmission of nerve impulse
Biological Process GO:0042060 wound healing

Reference

[1] Yao Y, Bade R, Li G, Zhang A, Zhao H et al.. Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia-Reperfusion Injury Rats.. Cell Mol Neurobiol 43(5):1989-2004. 2023 Jul. PMID: 36030297.

[2] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.

[3] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.