The phosphoinositide metabolic system | Sasaki Laboratory, Institute of Science Tokyo

The interconversion reactions of phosphoinositides are shown in a schematic with each phosphoinositide placed at a vertex of a cube. In mammals, most reactions are redundantly controlled by multiple enzymes.

Schematic of phosphoinositide interconversion. The eight species PI, PI3P, PI4P, PI5P, PI(3,4)P2, PI(3,5)P2, PI(4,5)P2, and PI(3,4,5)P3 are placed at the vertices and connected by kinase reactions (red solid lines, uppercase A–K) and phosphatase reactions (blue dashed lines, lowercase a–k). The number of enzymes catalyzing each reaction is shown on the right.

Legend for the reaction column

Uppercase (A–I) = phosphorylation reactions by kinases; lowercase (a–k) = dephosphorylation reactions by phosphatases. Reactions in parentheses are secondary or condition-dependent. Loci indicate chromosomal positions in human / mouse.

Phosphoinositide 3-kinase（PI3K）

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
Class IA PI3K	p110α	K (A, E)	PIK3CA	3q26	3B	PI3Kα / PIK3CA
	p110β	K (A, E)	PIK3CB	3q22	9E4	PI3Kβ / PIK3CB
	p110δ	K (A, E)	PIK3CD	1q36	4E2	PI3Kδ / PIK3CD
Class IB PI3K	p110γ	K (A, E)	PIK3CG	7q22	12B	PI3Kγ / PIK3CG
Class II PI3K	PI3K-C2α	A (E)	PIK3C2A	11q15	7F1	PIK3C2α / Cpk-m
	PI3K-C2β	A (E)	PIK3C2B	1q32	1E4	PIK3C2β
	PI3K-C2γ	A (E)	PIK3C2G	12q12	6G2	PIK3C2γ
Class III PI3K	Vps34	A	PIK3C3	18q12	18B1	PIK3C3

Phosphatidylinositol 4-kinase（PI4K）

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
Type II PI4K	PI4KIIα	B	PI4K2A	10q24	19C3	PI4K2A
	PI4KIIβ	B	PI4K2B	4q15	5C1	PI4K2B
Type III PI4K	PI4KIIIα	B	PIK4CA	22q11	16A3	PIK4CA / PI4KA
	PI4KIIIβ	B	PIK4CB	1q22	3F2.1	PIK4CB / PI4KB

Note: Type I PI4K was later found to be a PI3K.

Phosphatidylinositol phosphate kinase（PIPK）

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
Type I PIPK	PIPKIα	H	PIP5K1A	1q22	19C1	PIP5KIα / PIP5K1A （mouse PIPKIβ / PIP5K1B）
	PIPKIβ	H	PIP5K1B	9q13	3F2.1	PIP5KIβ / PIP5K1B （mouse PIPKIα / PIP5K1A）
	PIPKIγ	H	PIP5K1C	19p13	10C1	PIP5KIγ / PIP5K1C
Type II PIPK	PIPKIIα	I	PIP4K2A	10p12	2A3	PIP4K2A / PIP5K2A / PIP5KIIα
	PIPKIIβ	I	PIP4K2B	17q12	11D	PIP4K2B / PIP5K2B / PIP5KIIβ
	PIPKIIγ	I	PIP4K2C	12q13	10D3	PIP4K2C / PIP5K2C / PIP5KIIγ
Type III PIPK	PIPKIII	F (C)	PIP5K3	2p35	1C2	PIKfyve / p235 / PIP5K3

Phosphoinositide 3-phosphatase

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
PTEN	PTEN	e, k (a)	PTEN	10q23	19C1	MMAC1 / TEP1
Myotubularin	MTM1	a, g	MTM1	Xq28	XA7.2	CNM / MTMX / XLMTM
	MTMR1	a, g	MTMR1	Xq28	XA7.2
	MTMR2	a, g	MTMR2	11q21	9A1	CMT4B / CMT4B1
	MTMR3	a, g	MTMR3	22q12	11A1	FYVE-DSP1 / ZFYVE10
	MTMR4	a, g	MTMR4	17q22	11C	FYVE-DSP2 / ZFYVE11
	MTMR6	a (g)	MTMR6	13q12	14D1
	MTMR7	a	MTMR7	8p22	8B1.2
	MTMR8	(a)	MTMR8	Xq11	14D1	（mouse MTMR9）
	MTMR14	a, g	MTMR14	3p25	6E3	hJUMPY / hEDTP

Phosphoinositide 4-phosphatase

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
INPP4	INPP4A	d, (j)	INPP4A	2q11	1B	INPP4 type I
	INPP4B	d, (j)	INPP4B	4q31	8C2	INPP4 type II
PIP4P	PIP4P1	i	PIP4P1	14q11	14C1	TMEM55B
	PIP4P2	i	PIP4P2	8q21	4A1	TMEM55A

Phosphoinositide 5-phosphatase

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
Type II INPP5	SYNJ1	a, b, f, h, i, j	SYNJ1	21q22	16C3	synaptojanin 1 / INPP5G / PARK20
	SYNJ2	a, b, f, h, i, j	SYNJ2	6q25	17A1	synaptojanin 2 / INPP5H
	OCRL	h, j	OCRL	Xq26	10D3	OCRL1 / LOCR / Dent-2 / INPP5F
	INPP5B	h, j	INPP5B	1p34	4D2	5PTase / INPP5P
	INPP5J	h, j	INPP5J	22q12	11A1	PIPP / PIB5PA
	INPP5K	j, (h)	INPP5K	17p13	11B5	SKIP / PPS
Type III INPP5	SHIP1	j	INPP5D	2q37	1D
	SHIP2	j	INPPL1	11q13	7E2
Type IV INPP5	INPP5E	f, h, j	INPP5E	9q34	2A3	pharbin / MORMS / CPD4

Others

Class / Type	Protein	Reaction	Gene	Locus		Alias
Class / Type	Protein	Reaction	Gene	Human	Mouse	Alias
Sac	SAC1	a, b, (f)	SACM1L	3q21	9F4
	SAC2	h, j	INPP5F	10q26	7F3
	SAC3	f	FIG4	6q21	10B1	CMT4J / ALS11
VSP	VSP	e, h, j	TPTE2	13q12	8A2	TPIP / TPTE2 （mouse PTEN2）
PTPMT1	PTPMT1	c	PTPMT1	11p11.3	2E1	PLIP

Source: Based on materials from the Sasaki Laboratory (formerly Department of Pathophysiology / Lipid Biology). The classification of mammalian phosphoinositide-metabolizing enzymes follows Sasaki T et al., Prog Lipid Res 48:307–343, 2009.

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