CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-015178
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 
Protein Synonyms/Alias
 AblSH3-binding protein; Inositol polyphosphate phosphatase-like protein 1; INPPL-1; SH2 domain-containing inositol 5'-phosphatase 2; SH2 domain-containing inositol phosphatase 2; SHIP-2 
Gene Name
 Inppl1 
Gene Synonyms/Alias
 Ship2 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
332TKIGKSQKFTLSVDVubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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. Involved in endochondral ossification (By similarity). 
Sequence Annotation
 DOMAIN 21 117 SH2.
 DOMAIN 1195 1257 SAM.
 MOTIF 945 950 SH3-binding.
 MOTIF 984 987 NPXY motif.
 MOD_RES 165 165 Phosphothreonine (By similarity).
 MOD_RES 241 241 Phosphoserine (By similarity).
 MOD_RES 987 987 Phosphotyrosine (By similarity).
 MOD_RES 1136 1136 Phosphotyrosine (By similarity).
 MOD_RES 1161 1161 Phosphotyrosine (By similarity).  
Keyword
 Actin-binding; Cell adhesion; Cell projection; Complete proteome; Cytoplasm; Cytoskeleton; Hydrolase; Immunity; Membrane; Phosphoprotein; Reference proteome; SH2 domain; SH3-binding. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1257 AA 
Protein Sequence
MASVCGTPSP GGALGSPAPA WYHRDLSRAA AEELLARAGR DGSFLVRDSE SVAGAFALCV 60
LYQKHVHTYR ILPDGEDFLA VQTSQGVPVR RFQTLGELIG LYAQPNQGLV CALLLPVEGE 120
REPDPPDDRD ASDVEDEKPP LPPRSGSTSI SAPVGPSSPL PTPETPTTPA AESTPNGLST 180
VSHEYLKGSY GLDLEAVRGG ASNLPHLTRT LVTSCRRLHS EVDKVLSGLE ILSKVFDQQS 240
SPMVTRLLQQ QSLPQTGEQE LESLVLKLSV LKDFLSGIQK KALKALQDMS STAPPAPLQP 300
SIRKAKTIPV QAFEVKLDVT LGDLTKIGKS QKFTLSVDVE GGRLVLLRRQ RDSQEDWTTF 360
THDRIRQLIK SQRVQNKLGV VFEKEKDRTQ RKDFIFVSAR KREAFCQLLQ LMKNRHSKQD 420
EPDMISVFIG TWNMGSVPPP KNVTSWFTSK GLGKALDEVT VTIPHDIYVF GTQENSVGDR 480
EWLDLLRGGL KELTDLDYRP IAMQSLWNIK VAVLVKPEHE NRISHVSTSS VKTGIANTLG 540
NKGAVGVSFM FNGTSFGFVN CHLTSGNEKT TRRNQNYLDI LRLLSLGDRQ LSAFDISLRF 600
THLFWFGDLN YRLDMDIQEI LNYISRREFE PLLRVDQLNL EREKHKVFLR FSEEEISFPP 660
TYRYERGSRD TYAWHKQKPT GVRTNVPSWC DRILWKSYPE THIICNSYGC TDDIVTSDHS 720
PVFGTFEVGV TSQFISKKGL SKTSDQAYIE FESIEAIVKT ASRTKFFIEF YSTCLEEYKK 780
SFENDAQSSD NINFLKVQWS SRQLPTLKPI LADIEYLQDQ HLLLTVKSMD GYESYGECVV 840
ALKSMIGSTA QQFLTFLSHR GEETGNIRGS MKVRVPTERL GTRERLYEWI SIDKDDTGAK 900
SKVPSVSRGS QEHRSGSRKP ASTETSCPLS KLFEEPEKPP PTGRPPAPPR AVPREEPLNP 960
RLKSEGTSEQ EGVAAPPPKN SFNNPAYYVL EGVPHQLLPL EPPSLARAPL PPATKNKVAI 1020
TVPAPQLGRH RTPRVGEGSS SDEDSGGTLP PPDFPPPPLP DSAIFLPPNL DPLSMPVVRG 1080
RSGGEARGPP PPKAHPRPPL PPGTSPASTF LGEVASGDDR SCSVLQMAKT LSEVDYAPGP 1140
GRSALLPNPL ELQPPRGPSD YGRPLSFPPP RIRESIQEDL AEEAPCPQGG RASGLGEAGM 1200
GAWLRAIGLE RYEEGLVHNG WDDLEFLSDI TEEDLEEAGV QDPAHKRLLL DTLQLSK 1257 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
 GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
 GO:0005794; C:Golgi apparatus; IEA:Compara.
 GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:MGI.
 GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IEA:Compara.
 GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IEA:Compara.
 GO:0007015; P:actin filament organization; IEA:Compara.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0006897; P:endocytosis; IEA:Compara.
 GO:0006006; P:glucose metabolic process; IMP:MGI.
 GO:0032957; P:inositol trisphosphate metabolic process; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; IDA:MGI.
 GO:0008156; P:negative regulation of DNA replication; IEA:Compara.
 GO:0010629; P:negative regulation of gene expression; IMP:MGI.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Compara.
 GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IEA:Compara.
 GO:0043407; P:negative regulation of MAP kinase activity; IEA:Compara.
 GO:0010977; P:negative regulation of neuron projection development; IEA:Compara.
 GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IEA:Compara.
 GO:0006661; P:phosphatidylinositol biosynthetic process; IMP:MGI.
 GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
 GO:0009791; P:post-embryonic development; IMP:MGI.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0032868; P:response to insulin stimulus; IMP:MGI.
 GO:0097178; P:ruffle assembly; IMP:MGI. 
Interpro
 IPR005135; Endo/exonuclease/phosphatase.
 IPR000300; IPPc.
 IPR001660; SAM.
 IPR013761; SAM/pointed.
 IPR011510; SAM_2.
 IPR000980; SH2. 
Pfam
 PF03372; Exo_endo_phos
 PF07647; SAM_2
 PF00017; SH2 
SMART
 SM00128; IPPc
 SM00454; SAM
 SM00252; SH2 
PROSITE
 PS50105; SAM_DOMAIN
 PS50001; SH2 
PRINTS
 PR00401; SH2DOMAIN.