Page last updated: 2024-10-24

phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: phosphatidylinositol-3,5-bisphosphate + H2O = phosphatidylinositol-3-phosphate + orthophosphate. [PMID:10806194, PMID:16607019, RHEA:32955]

Phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity refers to the enzymatic hydrolysis of phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), a phosphoinositide lipid, into phosphatidylinositol-3-phosphate (PtdIns(3)P). This reaction is critical for regulating intracellular signaling pathways involved in various cellular processes, including membrane trafficking, cytoskeletal organization, and cell growth.

PtdIns(3,5)P2 is a key component of the endosomal pathway, where it acts as a signaling molecule to control the sorting and trafficking of membrane-bound proteins and lipids. Its dephosphorylation by 5-phosphatases is essential for maintaining proper endosomal function.

Specifically, the conversion of PtdIns(3,5)P2 to PtdIns(3)P by 5-phosphatases regulates the following events:

* **Endosome maturation:** PtdIns(3,5)P2 is enriched in early endosomes, where it promotes the formation of multivesicular bodies (MVBs). By converting PtdIns(3,5)P2 to PtdIns(3)P, 5-phosphatases contribute to the maturation of early endosomes into late endosomes, allowing for the delivery of cargo to lysosomes.
* **Recycling of membrane proteins:** PtdIns(3,5)P2 also plays a role in the recycling of membrane proteins from endosomes back to the plasma membrane. 5-phosphatases regulate this process by controlling the levels of PtdIns(3,5)P2 at the endosome membrane.
* **Regulation of autophagy:** PtdIns(3,5)P2 is involved in the initiation and progression of autophagy, a cellular process that breaks down and recycles cellular components. 5-phosphatases can influence autophagy by modulating the levels of PtdIns(3,5)P2, thereby affecting the formation of autophagosomes.

In addition to its role in endosomal function, PtdIns(3,5)P2 also has a regulatory influence on other cellular processes:

* **Cytoskeletal organization:** PtdIns(3,5)P2 interacts with proteins involved in actin cytoskeleton dynamics, influencing cell shape and motility.
* **Cell growth and proliferation:** PtdIns(3,5)P2 has been implicated in cell growth and proliferation, though its precise role in these processes is still being investigated.

Overall, phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity plays a critical role in regulating a wide range of cellular functions. Its precise role varies depending on the specific cell type and context, but its ability to control the levels of PtdIns(3,5)P2 makes it a key component in many intracellular signaling pathways.'
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Proteins (6)

ProteinDefinitionTaxonomy
1-phosphatidylinositol 3-phosphate 5-kinaseA 1-phosphatidylinositol 3-phosphate 5-kinase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2I7]Homo sapiens (human)
Synaptojanin-1A synaptojanin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43426]Homo sapiens (human)
Synaptojanin-2A synaptojanin-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15056]Homo sapiens (human)
1-phosphatidylinositol 3-phosphate 5-kinaseA 1-phosphatidylinositol 3-phosphate 5-kinase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2I7]Homo sapiens (human)
Synaptojanin-1A synaptojanin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43426]Homo sapiens (human)
Synaptojanin-2A synaptojanin-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15056]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
epicatechin gallate(-)-epicatechin-3-O-gallate : A gallate ester obtained by formal condensation of the carboxy group of gallic acid with the (3R)-hydroxy group of epicatechin. A natural product found in Parapiptadenia rigida.

epicatechin gallate: a steroid 5alpha-reductase inhibitor; RN given refers to the (cis)-isomer; structure given in first source; isolated from green tea
catechin;
gallate ester;
polyphenol
EC 3.2.1.1 (alpha-amylase) inhibitor;
EC 3.2.1.20 (alpha-glucosidase) inhibitor;
metabolite
ampelopsin(+)-dihydromyricetin : An optically active form of dihydromyricetin having (2R,3R)-configuration.

ampelopsin: hepatoprotective agent; isolated from Hovenia dulcis; RN given for (2R-trans)-isomer; structure in first source
dihydromyricetin;
secondary alpha-hydroxy ketone
antineoplastic agent;
antioxidant;
metabolite
epiafzelechin(-)-epiafzelechin : A catechin derivative having (2R,3R)-configuration.

epiafzelechin: antioxidant; 3'-deoxy form of epicatechin; structure in first source
catechinplant metabolite
pyrviniumpyrvinium : A quinolinium ion that is 1-methylquinolinium substituted by dimethylamino group at position 6 and a (E)-2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl at position 2. It is a anthelminthic drug active against pinworms. The salts of pyrvinium can also be used as anticancer agents.

pyrvinium: RN given refers to parent cpd; synonyms vanquin & vankin refer to pamoate[2:1]; structure in Merck Index, 9th ed, #7810
quinolinium ionanthelminthic drug;
antineoplastic agent
trans-2,3',4,5'-tetrahydroxystilbenetrans-2,3',4,5'-tetrahydroxystilbene: hydroxystilbene oxyresveratrolstilbenoid
chlorhexidinechlorhexidine : A bisbiguanide compound with a structure consisting of two (p-chlorophenyl)guanide units linked by a hexamethylene bridge.

Chlorhexidine: A disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque.
biguanides;
monochlorobenzenes
antibacterial agent;
antiinfective agent
vacuolin-1vacuolin-1: inhibits Ca2-dependent lysosomal exocytosis
ym 2016366-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide: an antiviral agent; structure in first sourcearomatic amide
apilimod
eriodictyol 7-O-beta-D-glucopyranosidebeta-D-glucoside;
flavanone glycoside;
monosaccharide derivative;
trihydroxyflavanone
plant metabolite;
radical scavenger
apy0201APY0201: a small molecular IL-12/23 inhibitor with pyrazolo[1,5-a]pyrimidine core; structure in first source