Gene/Proteome Database (LMPD)

LMPD ID
LMP001940
Gene ID
3636
Species
Homo sapiens (Human)
Gene Name
inositol polyphosphate phosphatase-like 1
Gene Symbol
INPPL1
Synonyms
OPSMD; SHIP2
Alternate Names
phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; SHIP-2; INPPL-1; 51C protein; protein 51C', "SH2 domain-containing inositol 5'-phosphatase 2", "SH2 domain-containing inositol-5'-phosphatase 2;,phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2
Chromosome
11
Map Location
11q13
EC Number
3.1.3.86
Summary
The protein encoded by this gene is an SH2-containing 5'-inositol phosphatase that is involved in the regulation of insulin function. The encoded protein also plays a role in the regulation of epidermal growth factor receptor turnover and actin remodelling. Additionally, this gene supports metastatic growth in breast cancer and is a valuable biomarker for breast cancer. [provided by RefSeq, Jan 2009]
Orthologs
View orthologs and multiple alignments for INPPL1

Proteins

phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Refseq ID NP_001558
Protein GI 222136583
UniProt ID O15357
mRNA ID NM_001567
Length 1258
RefSeq Status REVIEWED
MASACGAPGPGGALGSQAPSWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDGEDEKPPLPPRSGSTSISAPTGPSSPLPAPETPTAPAAESAPNGLSTVSHDYLKGSYGLDLEAVRGGASHLPHLTRTLATSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQNLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPQPSTRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNKHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKTLDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTARRNQNYLDILRLLSLGDRQLNAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRKEFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDEAGAKSKAPSVSRGSQEPRSGSRKPAFTEASCPLSRLFEEPEKPPPTGRPPAPPRAAPREEPLTPRLKPEGAPEPEGVAAPPPKNSFNNPAYYVLEGVPHQLLPPEPPSPARAPVPSATKNKVAITVPAPQLGHHRHPRVGEGSSSDEESGGTLPPPDFPPPPLPDSAIFLPPSLDPLPGPVVRGRGGAEARGPPPPKAHPRPPLPPGPSPASTFLGEVASGDDRSCSVLQMAKTLSEVDYAPAGPARSALLPGPLELQPPRGLPSDYGRPLSFPPPRIRESIQEDLAEEAPCLQGGRASGLGEAGMSAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK

Gene Information

Entrez Gene ID
3636
Gene Name
inositol polyphosphate phosphatase-like 1
Gene Symbol
INPPL1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005794 IDA:HPA C Golgi apparatus
GO:0042995 IEA:UniProtKB-KW C cell projection
GO:0005737 IDA:HPA C cytoplasm
GO:0005856 IEA:UniProtKB-KW C cytoskeleton
GO:0005829 TAS:Reactome C cytosol
GO:0005886 IEA:Ensembl C plasma membrane
GO:0042169 IPI:UniProtKB F SH2 domain binding
GO:0016787 IEA:UniProtKB-KW F hydrolase activity
GO:0007015 IMP:UniProtKB P actin filament organization
GO:0007155 TAS:UniProtKB P cell adhesion
GO:0001958 IMP:UniProtKB P endochondral ossification
GO:0006897 IMP:UniProtKB P endocytosis
GO:0006006 IEA:Ensembl P glucose metabolic process
GO:0002376 IEA:UniProtKB-KW P immune system process
GO:0043647 TAS:Reactome P inositol phosphate metabolic process
GO:0008285 IEA:Ensembl P negative regulation of cell proliferation
GO:0010629 IEA:Ensembl P negative regulation of gene expression
GO:0006661 TAS:Reactome P phosphatidylinositol biosynthetic process
GO:0046856 IEA:InterPro P phosphatidylinositol dephosphorylation
GO:0006644 TAS:Reactome P phospholipid metabolic process
GO:0009791 IEA:Ensembl P post-embryonic development
GO:0032868 IEA:Ensembl P response to insulin
GO:0097178 IEA:Ensembl P ruffle assembly
GO:0044281 TAS:Reactome P small molecule metabolic process

KEGG Pathway Links

KEGG Pathway ID Description
hsa04666 Fc gamma R-mediated phagocytosis
hsa04910 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_HUMAN
UniProt ID
O15357
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O15357-1; Sequence=Displayed; Name=2; IsoId=O15357-2; Sequence=VSP_027985;
Catalytic Activity 1-phosphatidyl-1D-myo-inositol 3,4,5- triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4- diphosphate + phosphate. {ECO
Disease Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM
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
Disease Opsismodysplasia (OPSMD) [MIM
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.
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.
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. {ECO
Induction By bacterial lipopolysaccharides (LPS).
Interaction P10275:AR; NbExp=3; IntAct=EBI-1384248, EBI-608057; P56945:BCAR1; NbExp=2; IntAct=EBI-1384248, EBI-702093; Q13480:GAB1; NbExp=2; IntAct=EBI-1384248, EBI-517684; Q8IV36:HID1; NbExp=2; IntAct=EBI-1384248, EBI-743438; Q15811-2:ITSN1; NbExp=9; IntAct=EBI-1384248, EBI-8052395; P08581:MET; NbExp=2; IntAct=EBI-1384248, EBI-1039152; Q9BX66:SORBS1; NbExp=5; IntAct=EBI-1384248, EBI-433642; O60504-1:SORBS3; NbExp=2; IntAct=EBI-1384248, EBI-1222953;
Miscellaneous Its ability to confer resistance to dietary obesity suggests that it may serve as a possible therapeutic target in cases of type 2 diabetes and obesity.
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
Sequence Caution Sequence=AAA50503.1; Type=Frameshift; Positions=1153; Evidence= ; Sequence=AAA96658.1; Type=Frameshift; Positions=Several; Evidence= ;
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
Subcellular Location Cytoplasm, cytosol. Cytoplasm, cytoskeleton. 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. {ECO
Tissue Specificity Widely expressed, most prominently in skeletal muscle, heart and brain. Present in platelets. Expressed in transformed myeloid cells and in primary macrophages, but not in peripheral blood monocytes. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/INPPL1ID40984ch11q13.html";

Identical and Related Proteins

Unique RefSeq proteins for LMP001940 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
222136583 RefSeq NP_001558 1258 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2

Identical Sequences to LMP001940 proteins

Reference Database Accession Length Protein Name
GI:222136583 GenBank EAW74855.1 1258 inositol polyphosphate phosphatase-like 1, isoform CRA_b [Homo sapiens]
GI:222136583 GenBank AAI40854.1 1258 Inositol polyphosphate phosphatase-like 1 [Homo sapiens]
GI:222136583 RefSeq XP_006718597.1 1258 PREDICTED: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X3 [Homo sapiens]
GI:222136583 SwissProt O15357.2 1258 RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; AltName: Full=Inositol polyphosphate phosphatase-like protein 1; Short=INPPL-1; AltName: Full=Protein 51C; AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2; Short=SH2 domain-containing inositol phosphatase 2; Short=SHIP-2 [Homo sapiens]

Related Sequences to LMP001940 proteins

Reference Database Accession Length Protein Name
GI:222136583 EMBL CAA74743.1 1258 inositol polyphosphate 5-phosphatase [Homo sapiens]
GI:222136583 GenBank AAT18821.1 1258 Sequence 1 from patent US 6703215
GI:222136583 GenBank ABA36712.1 1258 Sequence 1 from patent US 6936452
GI:222136583 GenBank ABJ28701.1 1258 Sequence 1 from patent US 7094546
GI:222136583 GenBank ACM82279.1 1254 Sequence 7777 from patent US 6812339
GI:222136583 GenBank JAA10604.1 1258 inositol polyphosphate phosphatase-like 1 [Pan troglodytes]