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Collapse Statistics
226 human active and 11 inactive phosphatases in total;
194 phosphatases have substrate data;
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305 protein substrates;
89 non-protein substrates;
1114 dephosphorylation interactions;
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213 KEGG pathways;
206 NCI Nature PID pathways
560 Reactome pathways;
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last update: 18 Feb, 2016

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INPPL1

Gene Name INPPL1 (QuickGO)
Structure of phosphatase catalytic domain

PDB ID: 3NR8
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SynonymsINPPL1 SHIP2
Protein NamePhosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2
Alternative Name(s)
Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 (EC 3.1.3.n1) (Inositol polyphosphate phosphatase-like protein 1) (INPPL-1) (Protein 51C) (SH2 domain-containing inositol-5'-phosphatase 2) (SH2 domain-containing inositol phosphatase 2) (SHIP-2)
Ensembl Gene IDENSG00000165458
EntrezGene ID3636
UniProt AC (Human)O15357 (protein sequence)
Enzyme ClassEC 3.1.3.n1 (BRENDA )
Molecular Weight138599
Protein Length1258
Phosphatase activityactive
Protein DomainInterPro | Pfam3D Structure * PDB | PDBe | DrugPort
* ModBase | SwissModel
Structure-based FamilyFamily 11 (CATH: 3.60.10.10)Historical ClassInositol-1,4,5-trisphosphate 5-phosphatase
Localization cytoplasm; cytoskeleton; cytosol; extracellular region; nucleus; plasma membrane (PubMed: 14718574, 11349134, 12847108, 11739414, 12676785 | Europe PMC)
Catalytic SiteCatalytic Site Atlas Target by Small MoleculesN/A
Gene ExpressionGene Expression Atlas

The Human Protein Atlas

Function and DiseaseOMIM
Protein-protein Interaction Database STRING | IntAct | MINT
Kinase Database Phospho.ELM | PhosphoSite | NetworKIN
Function (UniProt annotation)
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. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. 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 by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. 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. 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. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.
Catalytic Activity (UniProt annotation)
CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate.
Protein Sequence
MASACGAPGP GGALGSQAPS WYHRDLSRAA AEELLARAGR DGSFLVRDSE SVAGAFALCV LYQKHVHTYR ILPDGEDFLA VQTSQGVPVR RFQTLGELIG LYAQPNQGLV CALLLPVEGE REPDPPDDRD ASDGEDEKPP LPPRSGSTSI SAPTGPSSPL PAPETPTAPA AESAPNGLST VSHDYLKGSY GLDLEAVRGG ASHLPHLTRT LATSCRRLHS EVDKVLSGLE ILSKVFDQQS SPMVTRLLQQ QNLPQTGEQE LESLVLKLSV LKDFLSGIQK KALKALQDMS STAPPAPQPS TRKAKTIPVQ AFEVKLDVTL GDLTKIGKSQ KFTLSVDVEG GRLVLLRRQR DSQEDWTTFT HDRIRQLIKS QRVQNKLGVV FEKEKDRTQR KDFIFVSARK REAFCQLLQL MKNKHSKQDE PDMISVFIGT WNMGSVPPPK NVTSWFTSKG LGKTLDEVTV TIPHDIYVFG TQENSVGDRE WLDLLRGGLK ELTDLDYRPI AMQSLWNIKV AVLVKPEHEN RISHVSTSSV KTGIANTLGN KGAVGVSFMF NGTSFGFVNC HLTSGNEKTA RRNQNYLDIL RLLSLGDRQL NAFDISLRFT HLFWFGDLNY RLDMDIQEIL NYISRKEFEP LLRVDQLNLE REKHKVFLRF SEEEISFPPT YRYERGSRDT YAWHKQKPTG VRTNVPSWCD RILWKSYPET HIICNSYGCT DDIVTSDHSP VFGTFEVGVT SQFISKKGLS KTSDQAYIEF ESIEAIVKTA SRTKFFIEFY STCLEEYKKS FENDAQSSDN INFLKVQWSS RQLPTLKPIL ADIEYLQDQH LLLTVKSMDG YESYGECVVA LKSMIGSTAQ QFLTFLSHRG EETGNIRGSM KVRVPTERLG TRERLYEWIS IDKDEAGAKS KAPSVSRGSQ EPRSGSRKPA FTEASCPLSR LFEEPEKPPP TGRPPAPPRA APREEPLTPR LKPEGAPEPE GVAAPPPKNS FNNPAYYVLE GVPHQLLPPE PPSPARAPVP SATKNKVAIT VPAPQLGHHR HPRVGEGSSS DEESGGTLPP PDFPPPPLPD SAIFLPPSLD PLPGPVVRGR GGAEARGPPP PKAHPRPPLP PGPSPASTFL GEVASGDDRS CSVLQMAKTL SEVDYAPAGP ARSALLPGPL ELQPPRGLPS DYGRPLSFPP PRIRESIQED LAEEAPCLQG GRASGLGEAG MSAWLRAIGL ERYEEGLVHN GWDDLEFLSD ITEEDLEEAG VQDPAHKRLL LDTLQLSK
ELM motif
N/A
Gene Ontology
GO:0042169SH2 domain binding
GO:0017124SH3 domain binding
GO:0003779actin binding
GO:0030479actin cortical patch
GO:0007015actin filament organization
GO:0007155cell adhesion
GO:0005829cytosol
GO:0006897endocytosis

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