Overview
| Uniprot ID | Q13153 |
| Protein Name | Serine/threonine-protein kinase PAK 1 |
| Gene Name | PAK1 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 63 |
RSILPGDKTNKKKEK |
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:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). 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 (PubMed:12624090). 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 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). 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 (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). 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 (By similarity). 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 (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447)
Protein Sequence
10
MSNNGLDIQD
20
KPPAPPMRNT
30
STMIGAGSKD
40
AGTLNHGSKP
50
LPPNPEEKKK
60
KDRFYRSILP
70
GDKTNKKKEK
80
ERPEISLPSD
90
FEHTIHVGFD
100
AVTGEFTGMP
110
EQWARLLQTS
120
NITKSEQKKN
130
PQAVLDVLEF
140
YNSKKTSNSQ
150
KYMSFTDKSA
160
EDYNSSNALN
170
VKAVSETPAV
180
PPVSEDEDDD
190
DDDATPPPVI
200
APRPEHTKSV
210
YTRSVIEPLP
220
VTPTRDVATS
230
PISPTENNTT
240
PPDALTRNTE
250
KQKKKPKMSD
260
EEILEKLRSI
270
VSVGDPKKKY
280
TRFEKIGQGA
290
SGTVYTAMDV
300
ATGQEVAIKQ
310
MNLQQQPKKE
320
LIINEILVMR
330
ENKNPNIVNY
340
LDSYLVGDEL
350
WVVMEYLAGG
360
SLTDVVTETC
370
MDEGQIAAVC
380
RECLQALEFL
390
HSNQVIHRDI
400
KSDNILLGMD
410
GSVKLTDFGF
420
CAQITPEQSK
430
RSTMVGTPYW
440
MAPEVVTRKA
450
YGPKVDIWSL
460
GIMAIEMIEG
470
EPPYLNENPL
480
RALYLIATNG
490
TPELQNPEKL
500
SAIFRDFLNR
510
CLEMDVEKRG
520
SAKELLQHQF
530
LKIAKPLSSL
540
TPLIAAAKEA
TKNNH
Gene Ontology
| Classification |
GO ID |
Description |
| 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:0014704 |
intercalated disc |
| Cellular Component |
GO:0030027 |
lamellipodium |
| Cellular Component |
GO:0031965 |
nuclear membrane |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005886 |
plasma membrane |
| 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: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 |
| Biological Process |
GO:0030036 |
actin cytoskeleton organization |
| 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:0006974 |
DNA damage response |
| Biological Process |
GO:0048013 |
ephrin receptor signaling pathway |
| Biological Process |
GO:0030010 |
establishment of cell polarity |
| Biological Process |
GO:0006887 |
exocytosis |
| Biological Process |
GO:0038096 |
Fc-gamma receptor signaling pathway involved in phagocytosis |
| 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:0048812 |
neuron projection morphogenesis |
| 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: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:1903608 |
protein localization to cytoplasmic stress granule |
| Biological Process |
GO:0032956 |
regulation of actin cytoskeleton organization |
| Biological Process |
GO:0050770 |
regulation of axonogenesis |
| Biological Process |
GO:0043408 |
regulation of MAPK cascade |
| Biological Process |
GO:0001666 |
response to hypoxia |
| Biological Process |
GO:0002223 |
stimulatory C-type lectin receptor signaling pathway |
| Biological Process |
GO:0042060 |
wound healing |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.