INPPL1
entrez
3636
canonical
uniprot
O15357
canonical
ensembl
ENSG00000165458
resolver
ensp
ENSP00000298229
resolver
ensp
ENSP00000444619
resolver
ensp
ENSP00000595010
resolver
ensp
ENSP00000616962
resolver
ensp
ENSP00000735039
resolver
ensp
ENSP00000735040
resolver
ensp
ENSP00000735042
resolver
genesymbol
INPPL1
resolver
genesymbol_syn
SHIP2
resolver
hgnc
HGNC:6080
resolver
uniprot
B2RTX5
resolver
uniprot
Q13577
resolver
uniprot
Q13578
resolver
uniprot_entry
SHIP2_HUMAN
resolver
uniprot_sec
B2RTX5
resolver
uniprot_sec
Q13577
resolver
uniprot_sec
Q13578
resolver
activity_regulation
ACTIVITY REGULATION: Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is enhanced in the presence of phosphatidylserine. {ECO:0000269|PubMed:16824732}.
uniprot
proteins
amino_acid_sequence
MASACGAPGPGGALGSQAPSWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDGEDEKPPLPPRSGSTSISAPTGPSSPLPAPETPTAPAAESAPNGLSTVSHDYLKGSYGLDLEAVRGGASHLPHLTRTLATSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQNLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPQPSTRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNKHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKTLDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTARRNQNYLDILRLLSLGDRQLNAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRKEFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDEAGAKSKAPSVSRGSQEPRSGSRKPAFTEASCPLSRLFEEPEKPPPTGRPPAPPRAAPREEPLTPRLKPEGAPEPEGVAAPPPKNSFNNPAYYVLEGVPHQLLPPEPPSPARAPVPSATKNKVAITVPAPQLGHHRHPRVGEGSSSDEESGGTLPPPDFPPPPLPDSAIFLPPSLDPLPGPVVRGRGGAEARGPPPPKAHPRPPLPPGPSPASTFLGEVASGDDRSCSVLQMAKTLSEVDYAPAGPARSALLPGPLELQPPRGLPSDYGRPLSFPPPRIRESIQEDLAEEAPCLQGGRASGLGEAGMSAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK
uniprot
proteins
disease_involvement
DISEASE: Note=Genetic variations in INPPL1 may be a cause of susceptibility to metabolic syndrome. Metabolic syndrome is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia is absent. {ECO:0000269|PubMed:15220217, ECO:0000269|PubMed:17557929}.; DISEASE: Opsismodysplasia (OPSMD) [MIM:258480]: A rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with very delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges. {ECO:0000269|PubMed:23273569}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.3.86
uniprot
proteins
function
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 (PubMed:16824732). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:9660833). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (By similarity). Part of a signaling pathway that regulates actin cytoskeleton remodeling (PubMed:11739414, PubMed:12676785). 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 (PubMed:15668240). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading (PubMed:12235291). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (PubMed:15735664). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (PubMed:17135240). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (PubMed:12690104). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:11016922). Involved in EGF signaling pathway (PubMed:11349134). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (PubMed:11349134). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (PubMed:11349134). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (PubMed:23273569). {ECO:0000250|UniProtKB:F1PNY0, ECO:0000250|UniProtKB:Q6P549, ECO:0000250|UniProtKB:Q9WVR3, ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12676785, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15668240, ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:17135240, ECO:0000269|PubMed:21624956, ECO:0000269|PubMed:23273569, ECO:0000269|PubMed:9660833}.
uniprot
proteins
mass_dalton
138599
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="R->G: Abolishes interaction with p130Cas/BCAR1 and its ability to induce increased adhesion. Abolishes phosphorylation upon FCGR2A clustering."; /evidence="ECO:0000269|PubMed:11158326, ECO:0000269|PubMed:12690104"; MUTAGEN 140..141; /note="PL->AA: Abolishes interaction with SH3YL1."; /evidence="ECO:0000269|PubMed:21624956"; MUTAGEN 607; /note="D->A: Abolishes enzyme activity but not phosphorylation upon FCGR2A clustering."; /evidence="ECO:0000269|PubMed:12690104"; MUTAGEN 958; /note="T->A: Reduces PDGF-stimulated tyrosine phosphorylation and association with SHC1."; /evidence="ECO:0000269|PubMed:17219406"; MUTAGEN 986..987; /note="YY->FF: Inducer a strong reduction of phosphorylation upon re-plating on collagen I."; /evidence="ECO:0000269|PubMed:12235291
uniprot
proteins
post_translational_modification
PTM: Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as insulin, growth factors such as EGF or PDGF, chemokines, integrin ligands and hypertonic and oxidative stress. May be phosphorylated upon IgG receptor FCGR2B-binding. Phosphorylated at Tyr-986 following cell attachment and spreading. Phosphorylated at Tyr-1162 following EGF signaling pathway stimulation. Phosphorylated at Thr-958 in response to PDGF. {ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:11158326, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11687594, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:17219406, ECO:0000269|PubMed:9660833}.
uniprot
proteins
protein_family
4
uniprot
proteins
protein_family
5-trisphosphate 5-phosphatase family
uniprot
proteins
protein_family
Inositol 1
uniprot
proteins
pubmed
10194451
uniprot
proteins
pubmed
11016922
uniprot
proteins
pubmed
11158326
uniprot
proteins
pubmed
11349134
uniprot
proteins
pubmed
11687594
uniprot
proteins
pubmed
11739414
uniprot
proteins
pubmed
12235291
uniprot
proteins
pubmed
12504111
uniprot
proteins
pubmed
12676785
uniprot
proteins
pubmed
12690104
uniprot
proteins
pubmed
15220217
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15668240
uniprot
proteins
pubmed
15687335
uniprot
proteins
pubmed
15735664
uniprot
proteins
pubmed
16302969
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16824732
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17135240
uniprot
proteins
pubmed
17219406
uniprot
proteins
pubmed
17314030
uniprot
proteins
pubmed
17557929
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20933011
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21624956
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23273569
uniprot
proteins
pubmed
8530088
uniprot
proteins
pubmed
9367831
uniprot
proteins
pubmed
9660833
uniprot
proteins
sequence_length
1258
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11349134}. Cytoplasm, cytoskeleton. Membrane {ECO:0000269|PubMed:11739414}; Peripheral membrane protein. Cell projection, filopodium {ECO:0000269|PubMed:12676785}. Cell projection, lamellipodium {ECO:0000269|PubMed:12676785}. Basal cell membrane {ECO:0000250|UniProtKB:F1PNY0}. Nucleus {ECO:0000250|UniProtKB:D7PF45}. Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:F1PNY0}. Note=Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type (PubMed:11739414). Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B). Tyrosine phosphorylation may also participate in membrane localization. Insulin specifically stimulates its redistribution from the cytosol to the plasma membrane. Recruited to the membrane following M-CSF stimulation. In activated spreading platelets, localizes with actin at filopodia, lamellipodia and the central actin ring. {ECO:0000269|PubMed:11739414}.
uniprot
proteins