DegronMD - Q9Y2I7(PIKFYVE)

FUNCTION: Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:23086417). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:17556371). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:22621786). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:33098764). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (PubMed:30612035). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (By similarity). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (PubMed:30612035). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (By similarity). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, through association with SPAG9 and RABEPK (By similarity). Mediates EGFR trafficking to the nucleus (PubMed:17909029). {ECO:0000250|UniProtKB:Q9Z1T6, ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:22621786, ECO:0000269|PubMed:27623384, ECO:0000269|PubMed:28779020, ECO:0000269|PubMed:29584722, ECO:0000269|PubMed:30612035, ECO:0000269|PubMed:33098764, ECO:0000303|PubMed:23086417}.; FUNCTION: (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC) by endocytosis. {ECO:0000269|PubMed:32221306}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R1161I	TCGA-06-1087	GBM	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	TCGA-AA-3510	COAD	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	TCGA-AG-A002	READ	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	TCGA-B5-A1MR	UCEC	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	DO7783	COAD	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	DO222762	COCA	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	DO11549	GBM	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.R1161I	DO41758	UCEC	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.1944
p.T1799I	TCGA-19-5956	GBM	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	TCGA-AA-3845	COAD	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	TCGA-KN-8428	KICH	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	DO10020	COAD	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	DO228123	EOPC	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	DO13863	GBM	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	DO220484	KICH	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.T1799I	ACH-001061	Colon/Colorectal Cancer	CCLE	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1667
p.N310T	TCGA-24-1844	OV	TCGA	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.1667
p.N310T	DO30450	OV	ICGC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.1667
p.Q1800K	TCGA-32-2494	GBM	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1944
p.Q1800K	DO11998	GBM	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1944
p.A1818S	TCGA-34-5236	LUSC	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1111
p.A1818S	DO26778	LUSC	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1111
p.P1719L	TCGA-4Z-AA83	BLCA	TCGA	PKSSS	DEG_SPOP_SBC_1	1710:1714	Mutation rewiring degron network	0.1944
p.P1719L	DO51869	BLCA	ICGC	PKSSS	DEG_SPOP_SBC_1	1710:1714	Mutation rewiring degron network	0.1944
p.M1151K	TCGA-60-2725	LUSC	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.25
p.M1151K	DO26674	LUSC	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.25
p.K1174R	TCGA-66-2759	LUSC	TCGA	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.2778
p.K1174R	DO27326	LUSC	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.2778
p.K1801N	TCGA-AG-A002	READ	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation substituting flanking lysine	0.3333
p.R252Q	TCGA-AX-A2HC	UCEC	TCGA	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation altering degron motif	0.6218
p.R252Q	DO41572	UCEC	ICGC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation altering degron motif	0.6218
p.S1814L	TCGA-AZ-6598	COAD	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.2222
p.S1814L	DO10276	COAD	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.2222
p.S1814L	DO229272	THCA	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.2222
p.S1704N	TCGA-BR-8361	STAD	TCGA	PKSSS	DEG_SPOP_SBC_1	1710:1714	Mutation rewiring degron network	0.1667
p.S1704N	DO48032	STAD	ICGC	PKSSS	DEG_SPOP_SBC_1	1710:1714	Mutation rewiring degron network	0.1667
p.D247A	TCGA-CF-A9FH	BLCA	TCGA	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.2222
p.D247A	DO219000	BLCA	ICGC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.2222
p.R1158I	TCGA-CX-7086	HNSC	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.2778
p.R1158I	DO15046	HNSC	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.2778
p.R262H	TCGA-EO-A22U	UCEC	TCGA	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.1944
p.R262H	DO43755	UCEC	ICGC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.1944
p.G317C	TCGA-ER-A1A1	SKCM	TCGA	SGSPMVPSY	DEG_COP1_1	316:324	Mutation altering degron motif	0.6489
p.G317C	DO37413	SKCM	ICGC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation altering degron motif	0.6489
p.A1176T	TCGA-F4-6856	COAD	TCGA	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation altering degron motif	0.7139
p.A1176T	DO9114	COAD	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation altering degron motif	0.7139
p.R334Q	TCGA-F5-6814	READ	TCGA	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.0556
p.R334Q	DO36556	READ	ICGC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.0556
p.D1144N	TCGA-FI-A2D5	UCEC	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.0556
p.D1144N	DO41331	UCEC	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.0556
p.P1807S	TCGA-FS-A1ZZ	SKCM	TCGA	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation altering degron motif	0.6752
p.P1807S	DO37412	SKCM	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation altering degron motif	0.6752
p.A306T	TCGA-G4-6628	COAD	TCGA	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.0556
p.A306T	DO10132	COAD	ICGC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.0556
p.D1144G	TCGA-R3-A69X	BLCA	TCGA	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.0556
p.D1144G	DO51902	BLCA	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.0556
p.L246H	TCGA-VQ-A91D	STAD	TCGA	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.1944
p.L246H	DO51783	STAD	ICGC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.1944
p.E1189Q	DO225226	BRCA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.0833
p.D1154N	DO222451	BTCA	ICGC	DYR	CBL_MET	1154:1156	Mutation altering degron motif	0.6932
p.D1154N	DO229375	BTCA	ICGC	DYR	CBL_MET	1154:1156	Mutation altering degron motif	0.6932
p.M320I	DO6565	CLLE	ICGC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation altering degron motif	0.6507
p.L311M	DO44096	COAD	ICGC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.1944
p.Q1183K	DO229010	COCA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.25
p.Q1183K	DO229013	COCA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.25
p.Q1183K	DO229016	COCA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.25
p.Q1183K	DO229003	COCA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.25
p.Q1183K	DO229005	COCA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.25
p.K1819N	DO228974	LICA	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation substituting flanking lysine	0.1944
p.D1798Y	DO229029	LICA	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.1389
p.D1175Y	DO229035	LICA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.3056
p.A1153S	DO229038	LICA	ICGC	DYR	CBL_MET	1154:1156	Mutation rewiring degron network	0.3056
p.S1186I	DO229006	LICA	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.1667
p.K1174M	DO23250	LINC	ICGC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.2778
p.I1805L	DO222847	MELA	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation altering degron motif	0.6063
p.Q1803K	DO229213	THCA	ICGC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.2778
p.S1714N	SIDM02026	Colorectal Carcinoma	GDSC	PKSSS	DEG_SPOP_SBC_1	1710:1714	Mutation altering degron motif	0.818
p.I1805T	SIDM00845	Burkitt's Lymphoma	GDSC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation altering degron motif	0.7078
p.I1805T	SIDM01519	Head and Neck Carcinoma	GDSC	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation altering degron motif	0.7078
p.Q331H	SIDM00113	Kidney Carcinoma	GDSC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.1389
p.Q331H	TK10	kidney	COSMIC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.1389
p.N1188T	SIDM00009	Acute Myeloid Leukemia	GDSC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.1111
p.N1188T	ACH-002390	Leukemia	CCLE	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.1111
p.N1188T	MC-1010	haematopoietic and lymphoid tissue	COSMIC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation rewiring degron network	0.1111
p.S1178G	SIDM01435	Hepatocellular Carcinoma	GDSC	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation altering degron motif	0.6993
p.S1178G	ACH-000686	Liver Cancer	CCLE	ASSTS	DEG_SPOP_SBC_1	1176:1180	Mutation altering degron motif	0.6993
p.D1795H	ACH-000923	Lymphoma	CCLE	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation rewiring degron network	0.0556
p.P1807H	ACH-000946	Endometrial/Uterine Cancer	CCLE	INPHVE	LIG_APCC_ABBA_1	1805:1810	Mutation altering degron motif	0.7694
p.L322M	ACH-001642	Lymphoma	CCLE	SGSPMVPSY	DEG_COP1_1	316:324	Mutation altering degron motif	0.711
p.L322M	SCC-3	haematopoietic and lymphoid tissue	COSMIC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation altering degron motif	0.711
p.L252F	Sarc9371	bone	COSMIC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation altering degron motif	0.6981
p.Q245H	TK10	kidney	COSMIC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.1667
p.L333M	SCC-3	haematopoietic and lymphoid tissue	COSMIC	SGSPMVPSY	DEG_COP1_1	316:324	Mutation rewiring degron network	0.0833
p.L263F	Sarc9371	bone	COSMIC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation rewiring degron network	0.1667
p.V251F	MDST8	large intestine	COSMIC	PRTPVGS	DEG_SCF_FBW7_1	251:257	Mutation altering degron motif	0.7068

Kaplan plot for PIKFYVE in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

PIKFYVE

UniProt ID: Q9Y2I7

Entrez ID: 200576

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PIKFYVE in