DegronMD - O15530(PDPK1)

FUNCTION: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive. {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Q387P	TCGA-BG-A221	UCEC	TCGA	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.3056
p.S400Y	TCGA-D8-A27G	BRCA	TCGA	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.1111
p.S390L	TCGA-EO-A3AV	UCEC	TCGA	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation altering degron motif	0.7667
p.D394N	DO222798	COCA	ICGC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation blocking phosphorylation signal	0.7222
p.E389D	DO229026	LICA	ICGC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation altering degron motif	0.6758
p.S386I	DO229041	LICA	ICGC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.2778
p.G385S	DO49766	PRAD	ICGC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.25
p.G384C	SIDM00347	Esophageal Squamous Cell Carcinoma	GDSC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.2222
p.G384C	ACH-000408	Esophageal Cancer	CCLE	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.2222
p.G384C	TE-5	oesophagus	COSMIC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.2222
p.T402A	SIDM00217	Colorectal Carcinoma	GDSC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.T402A	ACH-000999	Colon/Colorectal Cancer	CCLE	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.T402A	SNU-1040	large intestine	COSMIC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.N378S	SIDM00604	Oral Cavity Carcinoma	GDSC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.N378S	ACH-001542	Head and Neck Cancer	CCLE	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.N378S	KON	upper aerodigestive tract	COSMIC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.Q387H	SIDM01510	Non-Small Cell Lung Carcinoma	GDSC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.3056
p.Q387H	ACH-000925	Lung Cancer	CCLE	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.3056
p.R378Q	HCC2998	large intestine	COSMIC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation rewiring degron network	0.0556
p.H390Q	JSC-1	haematopoietic and lymphoid tissue	COSMIC	VSSSS	DEG_SPOP_SBC_1	388:392	Mutation altering degron motif	0.7582

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

PDPK1

UniProt ID: O15530

Entrez ID: 5170

Protein name: 3-phosphoinositide-dependent protein kinase 1 (hPDK1) (EC 2.7.11.1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PDPK1 in