InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PAK1

Summary

InnateDB Protein

IDBP-65614.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PAK1

Protein Name

p21 protein (Cdc42/Rac)-activated kinase 1

Synonyms

PAKalpha;

Species

Homo sapiens

Ensembl Protein

ENSP00000348696

InnateDB Gene

IDBG-65610 (PAK1)

Protein Structure

UniProt Annotation

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. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. 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). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. 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. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. 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. In synapses, seems to mediate the regulation of F- actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. {ECO:0000269PubMed:10551809, ECO:0000269PubMed:11733498, ECO:0000269PubMed:12624090, ECO:0000269PubMed:12876277, ECO:0000269PubMed:14585966, ECO:0000269PubMed:15611088, ECO:0000269PubMed:15831477, ECO:0000269PubMed:15833848, ECO:0000269PubMed:16278681, ECO:0000269PubMed:17726028, ECO:0000269PubMed:17989089, ECO:0000269PubMed:22669945, ECO:0000269PubMed:23633677, ECO:0000269PubMed:8805275, ECO:0000269PubMed:9032240, ECO:0000269PubMed:9395435, ECO:0000269PubMed:9528787}.

Subcellular Localization

Cytoplasm. Cell junction, focal adhesion. Cell membrane. Cell projection, ruffle membrane. Note=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.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 161 experimentally validated interaction(s) in this database.
They are also associated with 20 interaction(s) predicted by orthology.

Experimentally validated
Total	161 [view]
Protein-Protein	160 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	20 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005518	collagen binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0006468	protein phosphorylation
GO:0006887	exocytosis
GO:0006915	apoptotic process
GO:0007015	actin filament organization
GO:0007411	axon guidance
GO:0023014	signal transduction by phosphorylation
GO:0031295	T cell costimulation
GO:0031532	actin cytoskeleton reorganization
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0033148	positive regulation of intracellular estrogen receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042060	wound healing
GO:0043507	positive regulation of JUN kinase activity
GO:0045087	innate immune response
GO:0046777	protein autophosphorylation
GO:0048754	branching morphogenesis of an epithelial tube
GO:0048812	neuron projection morphogenesis
GO:0050852	T cell receptor signaling pathway
GO:0051496	positive regulation of stress fiber assembly
GO:0060244	negative regulation of cell proliferation involved in contact inhibition

Cellular Component

GO:0001726	ruffle
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0005925	focal adhesion
GO:0014704	intercalated disc
GO:0030018	Z disc
GO:0030424	axon
GO:0030425	dendrite
GO:0031941	filamentous actin
GO:0031965	nuclear membrane
GO:0032587	ruffle membrane
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000095 CRIB domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011026 Wiscott-Aldrich syndrome protein, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00786
PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00285
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt