DegronMD - Q13153(PAK1)

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:11896197, PubMed:30290153). 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. 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). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:16278681, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R421L	TCGA-AA-3947	COAD	TCGA	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2778
p.R421L	DO8192	COAD	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2778
p.F410L	TCGA-AZ-4315	COAD	TCGA	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2222
p.F410L	DO8842	COAD	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2222
p.F410L	SIDM00217	Colorectal Carcinoma	GDSC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2222
p.F410L	ACH-000999	Colon/Colorectal Cancer	CCLE	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2222
p.F410L	SNU-1040	large intestine	COSMIC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.2222
p.L405I	TCGA-CV-A6JM	HNSC	TCGA	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.0833
p.L405I	DO49991	HNSC	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.0833
p.E417Q	TCGA-G2-AA3B	BLCA	TCGA	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation altering degron motif	0.5633
p.E417Q	DO51882	BLCA	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation altering degron motif	0.5633
p.T406N	DO228971	LICA	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.1111
p.T415N	DO228985	LICA	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation altering degron motif	0.8166
p.P416L	DO229494	SKCA	ICGC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation altering degron motif	0.7582
p.T406A	SIDM01045	Endometrial Carcinoma	GDSC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.1111
p.T406A	EN	endometrium	COSMIC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.1111
p.D407G	MFE-319	endometrium	COSMIC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation rewiring degron network	0.1389
p.V420L	H3255	lung	COSMIC	ITPEQS	DEG_SCF_FBW7_1	414:419	Mutation blocking ubiquitination signal	0.75

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PAK1

UniProt ID: Q13153

Entrez ID: 5058

Protein name: Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (Alpha-PAK) (p21-activated kinase 1) (PAK-1) (p65-PAK)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PAK1 in