Gene/Proteome Database (LMPD)

LMPD ID
LMP006572
Gene ID
16332
Species
Mus musculus (Mouse)
Gene Name
inositol polyphosphate phosphatase-like 1
Gene Symbol
Inppl1
Synonyms
51C; SHIP2
Alternate Names
phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; SHIP-2; INPPL-1; ablSH3-binding protein; SH2 domain-containing inositol phosphatase 2', "SH2 domain-containing inositol 5'-phosphatase 2", "SH2 domain-containing inositol-5'-phosphatase 2;,inositol polyphosphate phosphatase-like protein 1; phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2
Chromosome
7
Map Location
7 F1|7
EC Number
3.1.3.86

Proteins

phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Refseq ID NP_034697
Protein GI 170172575
UniProt ID Q6P549
mRNA ID NM_010567
Length 1257
RefSeq Status VALIDATED
MASVCGTPSPGGALGSPAPAWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDVEDEKPPLPPRSGSTSISAPVGPSSPLPTPETPTTPAAESTPNGLSTVSHEYLKGSYGLDLEAVRGGASNLPHLTRTLVTSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQSLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPLQPSIRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNRHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKALDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTTRRNQNYLDILRLLSLGDRQLSAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRREFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDDTGAKSKVPSVSRGSQEHRSGSRKPASTETSCPLSKLFEEPEKPPPTGRPPAPPRAVPREEPLNPRLKSEGTSEQEGVAAPPPKNSFNNPAYYVLEGVPHQLLPLEPPSLARAPLPPATKNKVAITVPAPQLGRHRTPRVGEGSSSDEDSGGTLPPPDFPPPPLPDSAIFLPPNLDPLSMPVVRGRSGGEARGPPPPKAHPRPPLPPGTSPASTFLGEVASGDDRSCSVLQMAKTLSEVDYAPGPGRSALLPNPLELQPPRGPSDYGRPLSFPPPRIRESIQEDLAEEAPCPQGGRASGLGEAGMGAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK
phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Refseq ID NP_001116211
Protein GI 170172577
UniProt ID Q6P549
mRNA ID NM_001122739
Length 1257
RefSeq Status VALIDATED
Protein sequence is identical to GI:170172575 (mRNA isoform)

Gene Information

Entrez Gene ID
16332
Gene Name
inositol polyphosphate phosphatase-like 1
Gene Symbol
Inppl1
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005794 IEA:Ensembl C Golgi apparatus
GO:0042995 IEA:UniProtKB-KW C cell projection
GO:0005737 IDA:MGI C cytoplasm
GO:0005856 IEA:UniProtKB-KW C cytoskeleton
GO:0005886 IDA:MGI C plasma membrane
GO:0016787 IEA:UniProtKB-KW F hydrolase activity
GO:0007015 IEA:Ensembl P actin filament organization
GO:0007155 IEA:UniProtKB-KW P cell adhesion
GO:0044255 IMP:MGI P cellular lipid metabolic process
GO:0001958 ISS:UniProtKB P endochondral ossification
GO:0006897 IEA:Ensembl P endocytosis
GO:0006006 IMP:MGI P glucose metabolic process
GO:0002376 IEA:UniProtKB-KW P immune system process
GO:0008285 IDA:MGI P negative regulation of cell proliferation
GO:0010629 IMP:MGI P negative regulation of gene expression
GO:0006661 IMP:MGI P phosphatidylinositol biosynthetic process
GO:0046856 IEA:InterPro P phosphatidylinositol dephosphorylation
GO:0009791 IMP:MGI P post-embryonic development
GO:0032868 IMP:MGI P response to insulin
GO:0097178 IMP:MGI P ruffle assembly

KEGG Pathway Links

KEGG Pathway ID Description
mmu04662 B cell receptor signaling pathway
mmu04666 Fc gamma R-mediated phagocytosis
mmu04910 Insulin signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR005135 Endonuclease/exonuclease/phosphatase
IPR000300 Inositol polyphosphate-related phosphatase
IPR000980 SH2 domain
IPR001660 Sterile alpha motif domain
IPR021129 Sterile alpha motif, type 1
IPR013761 Sterile alpha motif/pointed domain

UniProt Annotations

Entry Information

Gene Name
inositol polyphosphate phosphatase-like 1
Protein Entry
SHIP2_MOUSE
UniProt ID
Q6P549
Species
Mouse

Comments

Comment Type Description
Catalytic Activity 1-phosphatidyl-1D-myo-inositol 3,4,5- triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4- diphosphate + phosphate. {ECO:0000269|PubMed:10958682}.
Developmental Stage In E15.5 embryos, it is strongly expressed in the liver, specific regions of the central nervous system, the thymus, the lung, and the cartilage perichondrium. In adult it is markedly present in the brain and the thymus and at different stages of spermatozoa maturation in the seminiferous tubules. {ECO:0000269|PubMed:10610720}.
Disruption Phenotype Mice are viable, have normal glucose and insulin levels, and normal insulin and glucose tolerance. They are however highly resistant to weight gain when placed on a high-fat diet, suggesting that inhibition of Inppl1 would be useful in the effort to ameliorate diet-induced obesity. According to preliminary results from PubMed:11343120, mice display increased sensitivity to insulin, characterized by severe neonatal hypoglycemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death. They display increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the Slc2a4/Glut4 glucose transporter and increased glycogen synthesis in skeletal muscles. However, these knockout mice also contain a deletion of the last exon of Phox2a gene. It is therefore unknown whether the insulin sensitivity observed in these mice result from inactivation of either Inppl1 or Phox2a. {ECO:0000269|PubMed:11343120, ECO:0000269|PubMed:15654325}.
Domain The NPXY sequence motif found in many tyrosine- phosphorylated proteins is required for the specific binding of the PID domain. {ECO:0000250}.
Domain The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or FCGR2A. It also mediates the interaction with p130Cas/BCAR1 (By similarity). {ECO:0000250}.
Enzyme 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 (By similarity). {ECO:0000250}.
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. Involved in endochondral ossification (By similarity). {ECO:0000250}.
Induction Overexpressed in diabetic db/db mice. {ECO:0000269|PubMed:12145149}.
Interaction Q9Z0R4-2:Itsn1; NbExp=2; IntAct=EBI-2642932, EBI-8052786;
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-987 following cell attachment and spreading. Phosphorylated at Tyr- 1161 following EGF signaling pathway stimulation (By similarity). {ECO:0000250}.
Sequence Caution Sequence=AAI19454.1; Type=Erroneous initiation; Evidence={ECO:0000305};
Similarity Belongs to the inositol 1,4,5-trisphosphate 5- phosphatase family. {ECO:0000305}.
Similarity Contains 1 SAM (sterile alpha motif) domain. {ECO:0000255|PROSITE-ProRule:PRU00184}.
Similarity Contains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
Subcellular Location Cytoplasm, cytosol. Cytoplasm, cytoskeleton {ECO:0000250}. Membrane; Peripheral membrane protein. Cell projection, filopodium {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Note=Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. 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.
Subunit Interacts with tyrosine phosphorylated form of SHC1, Interacts with EGFR. Upon stimulation by the EGF signaling pathway, it forms a complex with SHC1 and EGFR. Interacts with cytoskeletal protein SORBS3/vinexin, promoting its localization to the periphery of cells. Forms a complex with filamin (FLNA or FLNB), actin, GPIb (GP1BA or GP1BB) that regulates cortical and submembraneous actin. Interacts with c-Met/MET, when c-Met/MET is phosphorylated on 'Tyr-1356'. Interacts with p130Cas/BCAR1. Interacts with CENTD3/ARAP3 via its SAM domain. Interacts with c- Cbl/CBL and CAP/SORBS1. Interacts with activated EPHA2 receptor. Interacts with receptors FCGR2A and FCGR2B. Interacts with tyrosine kinases ABL1 and TEC. Interacts with CSF1R. {ECO:0000269|PubMed:10789675, ECO:0000269|PubMed:15456754, ECO:0000269|PubMed:15492005, ECO:0000269|PubMed:15557176}.
Tissue Specificity Widely expressed. {ECO:0000269|PubMed:10610720}.

Identical and Related Proteins

Unique RefSeq proteins for LMP006572 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
170172575 RefSeq NP_034697 1257 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2

Identical Sequences to LMP006572 proteins

Reference Database Accession Length Protein Name
GI:170172575 GenBank AAH63080.1 1257 Inositol polyphosphate phosphatase-like 1 [Mus musculus]
GI:170172575 GenBank EDL16524.1 1257 inositol polyphosphate phosphatase-like 1, isoform CRA_c [Mus musculus]
GI:170172575 RefSeq NP_001116211.1 1257 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [Mus musculus]
GI:170172575 RefSeq XP_006507454.1 1257 PREDICTED: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [Mus musculus]
GI:170172575 SwissProt Q6P549.1 1257 RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; AltName: Full=AblSH3-binding protein; AltName: Full=Inositol polyphosphate phosphatase-like protein 1; Short=INPPL-1; AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2; Short=SH2 domain-containing inositol phosphatase 2; Short=SHIP-2 [Mus musculus]

Related Sequences to LMP006572 proteins

Reference Database Accession Length Protein Name
GI:170172575 DBBJ BAA82308.1 1257 SH2-containing inositol phosphatase 2 (SHIP2) [Rattus norvegicus]
GI:170172575 GenBank AAF28187.1 1257 SH2-containing inositol 5-phosphatase 2 [Mus musculus]
GI:170172575 RefSeq NP_075233.1 1257 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 1 [Rattus norvegicus]
GI:170172575 RefSeq XP_005074086.1 1257 PREDICTED: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [Mesocricetus auratus]
GI:170172575 RefSeq XP_005368851.1 1257 PREDICTED: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [Microtus ochrogaster]
GI:170172575 SwissProt Q9WVR3.1 1257 RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; AltName: Full=Inositol polyphosphate phosphatase-like protein 1; Short=INPPL-1; AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2; Short=SH2 domain-containing inositol phosphatase 2; Short=SHIP-2 [Rattus norvegicus]