DegronMD - Q99755(PIP5K1A)

FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:8955136, PubMed:21477596, PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (PubMed:19158393, PubMed:20660631). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Can also use phosphatidylinositol (PtdIns) as substrate in vitro (PubMed:22942276). Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity). Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup (By similarity). Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (By similarity). Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, IP3 and DAG, that will mobilize internal calcium and drive keratinocyte differentiation (PubMed:19158393). Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (By similarity). Together with PIP5K1C has a role during embryogenesis (By similarity). Independently of its catalytic activity, is required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of the small GTPase RAC1 to the plasma membrane (PubMed:20660631). Also functions in the nucleus where it acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs (PubMed:18288197). {ECO:0000250|UniProtKB:P70182, ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:19158393, ECO:0000269|PubMed:20660631, ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22942276, ECO:0000269|PubMed:8955136}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.G504V	TCGA-24-1469	OV	TCGA	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.0833
p.Q515E	TCGA-78-7539	LUAD	TCGA	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation altering degron motif	0.5633
p.Q515H	TCGA-DK-A3X1	BLCA	TCGA	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation altering degron motif	0.647
p.E524K	TCGA-ZF-AA51	BLCA	TCGA	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.2222
p.M503V	DO52752	CMDI	ICGC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.0556
p.T505S	DO233764	GACA	ICGC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.1111
p.H522Y	DO222908	MELA	ICGC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.2778
p.H522R	DO38483	STAD	ICGC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.2778
p.I528M	SIDM00319	Melanoma	GDSC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.1111
p.I528M	VMRC-MELG	skin	COSMIC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.1111
p.V505I	SIDM00220	Ovarian Carcinoma	GDSC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.1111
p.L507R	SIDM01577	Plasma Cell Myeloma	GDSC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.1667
p.P514L	SIDM01776	Plasma Cell Myeloma	GDSC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation altering degron motif	0.6471
p.L519S	ACH-000966	Ovarian Cancer	CCLE	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation altering degron motif	0.6556
p.I516M	ACH-001704	Skin Cancer	CCLE	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation altering degron motif	0.7618
p.I516M	VMRC-MELG	skin	COSMIC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation altering degron motif	0.7618
p.E511G	STS-0421	soft tissue	COSMIC	LPQTPPLE	DEG_SCF_FBW7_2	513:520	Mutation rewiring degron network	0.2778

Kaplan plot for PIP5K1A in

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

PIP5K1A

UniProt ID: Q99755

Entrez ID: 8394

Protein name: Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (PIP5K1-alpha) (PtdIns(4)P-5-kinase 1 alpha) (EC 2.7.1.68) (68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha) (Phosphatidylinositol 4-phosphate 5-kinase type I alpha) (PIP5KIalpha)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PIP5K1A in