UniProt functional annotation for Q8K337



	UniProt functional annotation for Q8K337

UniProt code: Q8K337.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5- trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. {ECO:0000269|PubMed:11311145, ECO:0000269|PubMed:9525932}.

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178, ChEBI:CHEBI:58456; EC=3.1.3.36; Evidence={ECO:0000269|PubMed:9525932};

Subunit: Interacts with APPL1, PHETA1 and PHETA2. Interacts with several Rab GTPases, at least RAB1A, RAB2A, RAB5A, RAB6A, RAB8A, RAB9A and RAB33B; these interactions may play a dual role in targeting INPP5B to the specific membranes and stimulating its phosphatase activity. Interacts preferentially with non-phosphorylated RAB8A; phosphoryation of RAB8A on 'Thr-72' disrupts this interaction (By similarity). Interacts with INPP5F (PubMed:25869668). {ECO:0000250|UniProtKB:P32019, ECO:0000269|PubMed:25869668}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:9525932}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000250|UniProtKB:P32019}. Early endosome membrane {ECO:0000250|UniProtKB:P32019}. Membrane {ECO:0000250|UniProtKB:P32019}; Peripheral membrane protein {ECO:0000250|UniProtKB:P32019}; Cytoplasmic side {ECO:0000250|UniProtKB:P32019}. Cytoplasmic vesicle, phagosome membrane {ECO:0000269|PubMed:9525932}.

Tissue specificity: Detected in kidney, liver, brain, lung and testis (at protein level). Detected in kidney and liver, and at lower levels in brain, lung and testis. {ECO:0000269|PubMed:9525932}.

Domain: The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature, all three interactions rely on F&H motifs, an approximately 12-13 amino- acid sequence centered around Phe and His residues essential for binding (By similarity). {ECO:0000250}.

Ptm: Isoprenylation at Cys-990 may be required for localization at the membrane. {ECO:0000250}.

Ptm: May be proteolytically cleaved after Lys-320 as inferred from N- terminal protein sequence of the 75 kda form. {ECO:0000250}.

Similarity: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family. {ECO:0000305}.

Sequence caution: Sequence=AAB95412.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5- trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. {ECO:0000269\|PubMed:11311145, ECO:0000269\|PubMed:9525932}.


Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178, ChEBI:CHEBI:58456; EC=3.1.3.36; Evidence={ECO:0000269\|PubMed:9525932};
Subunit:		Interacts with APPL1, PHETA1 and PHETA2. Interacts with several Rab GTPases, at least RAB1A, RAB2A, RAB5A, RAB6A, RAB8A, RAB9A and RAB33B; these interactions may play a dual role in targeting INPP5B to the specific membranes and stimulating its phosphatase activity. Interacts preferentially with non-phosphorylated RAB8A; phosphoryation of RAB8A on 'Thr-72' disrupts this interaction (By similarity). Interacts with INPP5F (PubMed:25869668). {ECO:0000250\|UniProtKB:P32019, ECO:0000269\|PubMed:25869668}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:9525932}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000250\|UniProtKB:P32019}. Early endosome membrane {ECO:0000250\|UniProtKB:P32019}. Membrane {ECO:0000250\|UniProtKB:P32019}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P32019}; Cytoplasmic side {ECO:0000250\|UniProtKB:P32019}. Cytoplasmic vesicle, phagosome membrane {ECO:0000269\|PubMed:9525932}.
Tissue specificity:		Detected in kidney, liver, brain, lung and testis (at protein level). Detected in kidney and liver, and at lower levels in brain, lung and testis. {ECO:0000269\|PubMed:9525932}.
Domain:		The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature, all three interactions rely on F&H motifs, an approximately 12-13 amino- acid sequence centered around Phe and His residues essential for binding (By similarity). {ECO:0000250}.
Ptm:		Isoprenylation at Cys-990 may be required for localization at the membrane. {ECO:0000250}.
Ptm:		May be proteolytically cleaved after Lys-320 as inferred from N- terminal protein sequence of the 75 kda form. {ECO:0000250}.
Similarity:		Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family. {ECO:0000305}.
Sequence caution:		Sequence=AAB95412.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};