Protein: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A (EC 3.1.3.86) (Inositol polyphosphate phosphatase-like protein 1A) (INPPL1-A) (SH2 domain-containing inositol 5'-phosphatase 2A) (SH2 domain-containing inositol phosphatase 2A) (SHIP-2A) (Q2I6J1)
Organism: Danio rerio (Zebrafish) (Brachydanio rerio)
Function: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin. Regulates cell adhesion and cell spreading. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6 (By similarity).
Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9WVR3}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:O15357}. Membrane {ECO:0000250|UniProtKB:Q9WVR3}; Peripheral membrane protein {ECO:0000250}. Cell projection, filopodium {ECO:0000250|UniProtKB:O15357}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:O15357}. Nucleus {ECO:0000250|UniProtKB:D7PF45}. Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Note=Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. {ECO:0000250}.
Interaction partners:
- Phosphatidylinositol 3-kinase regulatory subunit alpha
- Phosphatidylinositol 3-kinase regulatory subunit beta)
- Phosphoinositide-3-kinase, regulatory subunit, polypeptide 3
- Phosphatase and tensin homolog A
- Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2B
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit.
- phosphatidylinositol-4,5-bisphosphate 3-kinase
- Phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma
- Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
Sequence:
MAAVGPASPPPPPLWMHRDLSRAAAEELLARAGRDGSFLVRDSESVSGAYALCVLFQKHVHTYRILPDEENFLAVQTSQGVQPKRFKTLPELIQLYLQPSQGLVTTLLYPVEREETTEDRDYSDGEDEKPPLPPRTASTSSMTGSALVSTDTPPENVTAANGLSTISHEYLKGNYALDLEAVKQGANSLPHLNKTLLSSCKRLHGEVDKVLCGLEILSKVFDQQSASMVSRMIQQSMSQGGDQELEHLVTKLAILKDLLSSIEKKALKALQDMSSSTPAISPLLSIRNKVIPVQTFEVKLDVYLADLTKIGKSQKYSLSVDVEGGKLVVMKKMKDAQEDWNTFTHDKIRQLIKSQRVQNKLGIVFEKEKDKSQRKDFIFASAKKREAFCQLLQLMKNKHSNQDEPDMISIFIGTWNMGSVPAPKPLGSWILSRGLGKTLDEMAVTIPHDIYVFGTQENSVCDKEWVETLRCSLKEYTDMEYKPIAVQTLWNIKIVVLVKAEHENRISHVGMSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKIHRRNQNYLDILRQLSLGDKQLNSFDISLRFTHLFWFGDLNYRLDMDIQEILNYINRKEFDPLLKVDQLNLEREKNKIFLRFAEEEISYPPTYRYERGSRDTYVWQKQKATGMRTNVPSWCDRILWKSYPETHIVCNSYGCTDDIVTSDHSPVFGTFEVGVTSQFVSKKGLPKSSEQAYIEFENIEAIVKTASRTKFFIEFYSTCLEEFKKSYENDTQSSDNVNFLRVGWSSKQLTTLKPILSDIEYLQDQHLLLTVKSLDGYESYGECVLALKSMIGSTAQQFHTYLSHRGEETGNIRGSMRVRVPSERMGTRERLYEWISVDKDDMGGPKGRTLPPRTSHDYVKPTSSSSSRKHGSAELSRVSEEGEKSSTSRHTHTKEENTHNRGKQDPFESDATTCKNSFNNPAYYILEGVPNQSAALASDILPGSALPPLANKTTAPPAGSVGKSKPPSGSSAQGRWQTSGRSVRPISEEGSSEDDGNIGPHTGSLNRPPPDFPPPPLPKAALEMSENSFGKPRVFSDLADGKIPPPSKPLVSPGLTPPPGGAPGGGVAFCIESPPVLSPNSAPFRRGGGASALDDQSCSVLQMAKTLSEVEYPSGRERGASQGPTGPQLRGLSFPSHPIQEESIAEDLPEEGGLWGAESSSSSLSVDCSVGEWLQKLGLQHYEEGLLHNGWDDLEFLSDITEEDLEEAGVRDPAHKKILLASLKQQQK