Gene/Proteome Database (LMPD)
LMPD ID
LMP012725
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
inositol polyphosphate phosphatase-like 1
Gene Symbol
Synonyms
Ship2;
Alternate Names
phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; SHIP-2; INPPL-1; SH2-containing inositol phosphatase 2; 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
1
Map Location
1q32
EC Number
3.1.3.86
Summary
phosphatase that plays a negative regulatory role in insulin-induced mitogenesis [RGD, Feb 2006]
Orthologs
Proteins
| phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 1 | |
|---|---|
| Refseq ID | NP_075233 |
| Protein GI | 12621112 |
| UniProt ID | Q9WVR3 |
| mRNA ID | NM_022944 |
| Length | 1257 |
| MASVCGAPSPGGALGSQAPAWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDVEDEKPPLPPRSGSTSISVPAGPSSPLPAPETPTTPAAESTPNGLSTVSHEYLKGSYGLDLEAVRGGASNLPHLTRTLVTSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQSLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPLQPSIRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNKHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKALDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTTRRNQNYLDILRLLSLGDRQLSAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRREFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDDTGAKSKAPSVLRGSQEHRSGSRKPTSTEASCPLSKLFEEPEKPPPTGRPPAPPRAVPREESLNPRLKSEGTPEQEGVAAPPPKNSFNNPAYYVLEGVPHQLLPLEPTSFARAPIPPTTKNKVAITVPAPQLGRHRTPRVGEGSSSDEDSGGTLPPPDFPPPPLPDSAIFLPPNLDPLSMPVVRGRSVGEARGPPPPKAHPRPPLPPGTSPASTFLEEVASADDRSCSVLQMAKTLSEVDYSPGPGRSALLPNPLELQLPRGPSDYGRPLSFPPPRIRESIQEDLAEEAPCPQGGRASGLGEAGMGAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK | |
| phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 2 | |
|---|---|
| Refseq ID | NP_001257772 |
| Protein GI | 399220355 |
| UniProt ID | Q9WVR3 |
| mRNA ID | NM_001270843 |
| Length | 1183 |
| MASVCGAPSPGGALGSQAPAWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDVEDEKPPLPPRSGSTSISVPAGPSSPLPAPETPTTPAAESTPNGLSTVSHEYLKGSYGLDLEAVRGGASNLPHLTRTLVTSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQSLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPLQPSIRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNKHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKALDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTTRRNQNYLDILRLLSLGDRQLSAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRREFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDDTGAKSKAPSVLRGSQEHRSGSRKPTSTEASCPLSKLFEEPEKPPPTGRPPAPPRAVPREESLNPRLKSEGTPEQEGVAAPPPKNSFNNPAYYVLEGVPHQLLPLEPTSFARAPIPPTTKNKVAITVPAPQLGRHRTPRVGEGSSSDEDSGGTLPPPDFPPPPLPDSAIFLPPNLDPLSMPVVRGRSVGEARGPPPPKAHPRPPLPPGTSPASTFLEEVASADDRSCSVLQMAKTLSEVDYSPGPGRSALLPNPLELQLPRGPSDYGRPLSFPPPRIRESIQEDLAEE | |
Gene Information
Entrez Gene ID
Gene Name
inositol polyphosphate phosphatase-like 1
Gene Symbol
Species
Rattus norvegicus
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IEA:UniProtKB-KW | C | cytoplasm |
| GO:0005856 | IEA:UniProtKB-KW | C | cytoskeleton |
| GO:0030027 | IDA:RGD | C | lamellipodium |
| GO:0016020 | IEA:UniProtKB-KW | C | membrane |
| GO:0004445 | IDA:RGD | F | inositol-polyphosphate 5-phosphatase activity |
| GO:0005547 | IDA:RGD | F | phosphatidylinositol-3,4,5-trisphosphate binding |
| GO:0007420 | IEP:RGD | P | brain development |
| GO:0007155 | IEA:UniProtKB-KW | P | cell adhesion |
| GO:0001958 | ISS:UniProtKB | P | endochondral ossification |
| GO:0002376 | IEA:UniProtKB-KW | P | immune system process |
| GO:0032957 | IDA:RGD | P | inositol trisphosphate metabolic process |
| GO:0008156 | IMP:RGD | P | negative regulation of DNA replication |
| GO:0043407 | IMP:RGD | P | negative regulation of MAP kinase activity |
| GO:0046627 | IMP:RGD | P | negative regulation of insulin receptor signaling pathway |
| GO:0043569 | IMP:RGD | P | negative regulation of insulin-like growth factor receptor signaling pathway |
| GO:0010977 | IMP:RGD | P | negative regulation of neuron projection development |
| GO:0010642 | IMP:RGD | P | negative regulation of platelet-derived growth factor receptor signaling pathway |
| GO:0046856 | IEA:InterPro | P | phosphatidylinositol dephosphorylation |
| GO:0042493 | IEP:RGD | P | response to drug |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| ko04662 | B cell receptor signaling pathway |
| rno04662 | B cell receptor signaling pathway |
| ko04666 | Fc gamma R-mediated phagocytosis |
| rno04666 | Fc gamma R-mediated phagocytosis |
| ko00562 | Inositol phosphate metabolism |
| rno00562 | Inositol phosphate metabolism |
| ko04910 | Insulin signaling pathway |
| rno04910 | Insulin signaling pathway |
| ko04070 | Phosphatidylinositol signaling system |
| rno04070 | Phosphatidylinositol signaling system |
Domain Information
UniProt Annotations
Entry Information
Gene Name
inositol polyphosphate phosphatase-like 1
Protein Entry
SHIP2_RAT
UniProt ID
Species
Rat
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9WVR3-1; Sequence=Displayed; Name=2; IsoId=Q9WVR3-2; Sequence=VSP_027986; |
| Catalytic Activity | 1-phosphatidyl-1D-myo-inositol 3,4,5- triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4- diphosphate + phosphate. |
| Domain | The NPXY sequence motif found in many tyrosine- phosphorylated proteins is required for the specific binding of the PID domain |
| 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) |
| 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) |
| 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) |
| Polymorphism | Variant Cys-1142 found in diabetic GK strain may be a cause of diabete in this strain. Genetic variations in Inppl1 may also be a cause of susceptibility to hypertension. |
| 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) |
| Similarity | Belongs to the inositol 1,4,5-trisphosphate 5- phosphatase family |
| Similarity | Contains 1 SAM (sterile alpha motif) domain |
| 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 . Cell projection, lamellipodium . 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 (By similarity) |
Identical and Related Proteins
Unique RefSeq proteins for LMP012725 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 12621112 | RefSeq | NP_075233 | 1257 | phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 1 |
| 399220355 | RefSeq | NP_001257772 | 1183 | phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 2 |
Identical Sequences to LMP012725 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:12621112 | DBBJ | BAA82308.1 | 1257 | SH2-containing inositol phosphatase 2 (SHIP2) [Rattus norvegicus] |
| GI:12621112 | 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] |
Related Sequences to LMP012725 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:12621112 | DBBJ | BAA82308.1 | 1257 | SH2-containing inositol phosphatase 2 (SHIP2) [Rattus norvegicus] |
| GI:399220355 | DBBJ | BAA82308.1 | 1257 | SH2-containing inositol phosphatase 2 (SHIP2) [Rattus norvegicus] |
| GI:399220355 | RefSeq | NP_075233.1 | 1257 | phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 1 [Rattus norvegicus] |
| GI:12621112 | RefSeq | XP_006507454.1 | 1257 | PREDICTED: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [Mus musculus] |
| GI:399220355 | 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] |
| GI:12621112 | 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] |