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INPPL1 (inositol polyphosphate phosphatase-like 1)

Written2009-06Nagendra K Prasad
Purdue Cancer Center, Purdue Oncological Sciences Center, Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)EC 3.1.3.n1
HGNC Alias symbSHIP2
HGNC Alias name51C protein
 SH2 domain-containing inositol 5'-phosphatase 2
 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
LocusID (NCBI) 3636
Atlas_Id 40984
Location 11q13.4  [Link to chromosome band 11q13]
Location_base_pair Starts at 72224767 and ends at 72239144 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping INPPL1.png]
Local_order 71578250 FOLR1-FOLR2-INPPL1-PHOX2A 71669874 (Entrez data).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
INPPL1 (11q13.4)::CD2BP2 (16p11.2)INPPL1 (11q13.4)::COIL (17q22)INPPL1 (11q13.4)::INPPL1 (11q13.4)
INPPL1 (11q13.4)::NPM1 (5q35.1)


Description The cDNA sequence for human SHIP2 is 3777 nucleotide long (full processed mRNA is 4733 ntd long) (Hejna et al., 1995; Pesesse et al., 1997). The coding region comprises 28 exons. There is evidence for the existence of a shorter transcript (372 ntd long of unknown significance coding for 123 amino acids. The C-terminus 74 codons (including the SAM-domain) are common for both the transcripts.
Transcription SHIP2 promoter is regulated by Sp1 transcription factors (Ishida et al., 2005). Mechanisms of transcriptional regulations are unknown and perhaps not present. SHIP2 mRNA is expressed ubiquitously at high levels (Pesesse et al., 1997; Habib et al., 1998) and the protein levels are regulated post-transcriptionally by microRNA-205 (inhibitory) or microRNA-184 (which is a suppressor of mir-205) (Yu et al., 2008).


  Structural features of SHIP2 protein: The positions of the SHIP2 catalytic domain and the protein interaction motifs are shown. Currently known SHIP2-interacting proteins are listed under the respective interaction domain/motifs. SH2 (src homology-2 domain), IPPc (inositol polyphosphate phosphatase catalytic domain), Pro-rich (proline rich region), SAM (sterile alpha-motif).
Description SHIP2 protein (1258 amino acids long) contains an inositol polyphosphate phosphatase domain (IPPc; aa 422-735). In addition, SHIP2 has an amino-terminal SH2-domain (aa 21-117) and a carboxyl-terminal proline-rich region (Pro-rich; aa 935-1105). Also, SHIP2 contains a NPXY motif (aa 983-986) and a SAM (sterile alpha-motif) domain (aa 1201-1258). These structural elements provide sites for protein-protein interactions which seem to play a major role in SHIP2 function. Several cellular proteins associate with SHIP2 via phosphotyrosine-dependent (SH2 or NPXY mediated) or proline-rich region (SH3 mediated) interactions (for a comprehensive list of interacting proteins and citations please see Prasad, 2009a).
Expression Ubiquitously expressed with higher levels of mRNA in skeletal muscle, liver, adipose tissue, placenta and brain (Pesesse et al., 1997; Habib et al., 1998; Muraille et al., 2001). Also expressed in B-cells, T-cells, platelets, mast cells and macrophages (Muraille et al., 1999; Dyson et al., 2003; Giuriato et al., 2003; Ai et al., 2006; Leung and Bolland, 2007). Protein levels are very low in normal tissues and cells. Higher levels of protein expression is noted in many types of cancer cells (Wisniewski et al., 1999; Prasad et al., 2001; Prasad and Decker 2005) and in human breast cancer tissues (Prasad et al., 2008). SHIP2 protein levels in skeletal muscle and fat are higher in obese db/db mice as compared to normal heterozygous (db/+) mice and SHIP2 protein levels are moderately increased in response to a high-fat diet in normal mice (Hori et al., 2002). SHIP2 genetic sequence in diabetic rats and humans contain mutations that may lead to increased levels of SHIP2 (Marion et al., 2002).
Localisation SHIP2 is diffusely cytoplasmic but membrane enrichment of SHIP2 occurs during cell attachment (Prasad et al., 2001), membrane ruffling (Dyson et al., 2001) or in response to m-CSF in macrophages (Wang et al., 2004). Mutation in the SH2-domain (R47G) causes punctate distribution pattern in the cytoplasm of HeLa cells (Prasad et al., 2001). SHIP2 has also been reported to localize to the nuclear speckles in vascular smooth muscle cells (Deleris et al., 2003).
Function Overview. Phosphoinositide (PI) lipids are important second messengers in the intracellular signaling pathways. PI lipids interact with the pleckstrin homology domain (PH-domain) containing cellular enzymes causing their membrane recruitment and/or allosteric activation. Phosphoinositide 3-kinase (PI3-kinase) is central to the signal-induced generation of new phosphoinositides and its activation is a key intermediate step in the signaling initiated by various external signals including many hormones (insulin and leptin), growth factors (EGF, IGF-1 and PDGF) as well as integrin ligation. SHIP2 dephosphorylates the 5-position of phosphatidylinositol-3,4,5-trisphosphate (PIP3) generated by the PI3-kinase, producing a new second messenger PI-3,4-bisphosphate (PI-3,4-P2). As PI3-kinase pathway aberrations play a major role in the development of cancer, diabetes and inflammation, SHIP2 function is expected to be critically important for the molecular pathogenesis of these diseases. SHIP2 also dephosphorylates PI-3,4-bisphosphate (Taylor et al., 2000). In vitro, a soluble inositol molecule, inositol-1,3,4,5-tetrakisphosphate (IP4) also serves as a high affinity substrate for SHIP2 (Pesesse et al., 1998; Chi et al., 2004; Batty et al., 2007).

Negative Regulator of insulin signaling. In cell culture overexpression studies, SHIP2 acts a mild suppressor of insulin signaling (Sasaoka et al., 2001; Wada et al., 2001). RNA interference studies, however, contradict these observations (Zhou et al., 2004; Huard et al., 2007). SHIP2 null-mice are viable but resistant to high-fat-diet-induced obesity (Sleeman et al., 2005). Insulin signaling was enhanced only modestly in these mice. However, liver-specific suppression of SHIP2 function in mice improves insulin function (Fukui et al., 2005; Grempler et al., 2007). Mechanisms by which SHIP2 achieves the energy homeostasis therefore remain unclear at present.

Negative Regulator of IGF-1 signaling. Exogenous SHIP2 in C2C12 skeletal muscle cells is shown to suppress IGF-1 signaling and to interfere with IGF-1-induced muscle hypertrophy (Rommel et al., 2001). Similarly SHIP2 blocks compensatory hypertrophy upon its exogenous expression in rat skeletal muscle myocytes (Bodine et al., 2001).

Positive Regulator of cytoskeleton remodeling, cell adhesion, lamellipodia formation/cell spreading. Transient exogenous expression of the wild type-SHIP2 increases cellular adhesion in SH2-domain dependent manner in HeLa cells (Prasad et al., 2001). Furthermore, catalytic activity of SHIP2 is important for efficient lamellipodia formation and cell spreading (Prasad et al., 2001). Interaction with c-Met is important for this function of SHIP2 in MDCK cells (Koch et al., 2005). Also, C-terminus proline-rich region of SHIP2 is shown to be important for membrane ruffling process through its interaction with Filamin (Dyson et al., 2003). Src kinase-induced tyrosine phosphorylation of SHIP2 and consequent SHIP2-Shc association are important for HeLa cell spreading on type I collagen (Prasad et al., 2002). In MDA-231 breast cancer cells, SHIP2 promotes cell migration and this effect is associated to sustained EGFR-Akt signaling and increased expression of chemokine receptor CXCR4 (Prasad, 2009b).

Negative Regulator of endocytosis (EGFR, Transferrin receptor, EphA2). Suppression of endogenous SHIP2 in cancer cells (HeLa cervical cancer cells and MDA-231 breast cancer cells) decreases ligand-induced endocytosis of the EGFR and EphA2 (Prasad and Decker, 2005; Zhuang et al., 2007). SHIP2 function in the endocytosis of EGFR is characterized by a direct and constitutive association between SHIP2 and c-Cbl ubiquitin ligase and changes in EGFR-Cbl association. Whereas SHIP2 directly interacts with EphA2 via SAM-domain and this interaction may be important for EphA2 endocytosis (Zhuang et al., 2007). SHIP2 associates with intersectin 1, a major regulator of EGFR endocytosis, and recruits it to the plasma membrane in response to EGF treatment (Xie et al., 2008).

Regulator of Cell Cycle progression and apoptosis. Early studies indicated a positive association between SHIP2 expression and cell proliferation where EGF increases the SHIP2 mRNA expression in thyrocytes (Pesesse et al., 1997). In addition, SHIP2 protein expression correlates with the EGFR expression in proliferating neurospheres (Muraille et al., 2001). Exogenous overexpression (using adenovirus vectors) of wild-type SHIP2 inhibits cell cycle progression in U87-MG glioblastoma cells (Taylor et al., 2000) and K562 leukemia cells (Giuriato et al., 2002) and of a dominant-negative SHIP2 (phosphatase-defective) increases proliferation of pancreatic beta-cells (Grempler et al., 2007). Whereas retroviral-mediated expression of SHIP2 does not inhibit cell cycle progression of Myeloma cells (Choi et al., 2002). Furthermore, RNAi-mediated suppression of endogenous SHIP2 in MDA-231 cells inhibits cell proliferation with G1 accumulation and decreased S-phase and delays in vivo tumorigenesis (Prasad et al., 2008). Retroviral-mediated expression of a catalytically inactive SHIP2 inhibits PDGF-induced proliferation of 3T3-L1 preadipocytes (Artemenko et al., 2009). Thus, this aspect of SHIP2 function appears to be influenced greatly by the experimental approach and/or the cell types employed.

Negative regulator of immune cell function. SHIP2 inhibits Fcgamma Receptor IIa signaling including Akt activation and NF-kb-dependent gene trasncription (Pengal et al., 2003), downregulates Fcgamma Receptor-mediated phagocytosis (Ai et al., 2006) and decreases mast cell degranulation (Leung and Bolland, 2007; Saini et al., 2009).

Homology SHIP2 is structurally related to SHIP1, another phosphoinositol 5-phosphatase expressed exclusively in hematopoietic tissues. SHIP1 is an important negative regulator of immune receptor and cytokine signaling. SHIP1 and SHIP2 show 64% identity in their inositol phosphatase domains and 54% identity in their SH2-domains. The C-terminus proline-rich region carries the least similarity (also the SAM-domain is present only in SHIP2 and not in SHIP1) and appears to be the key for functional divergence between these two enzymes. In addition to the human gene, SHIP2 gene has been cloned from mouse, rat, cattle, dog, monkey, chimpanzee and zebra fish genomes.


Germinal There is R1142C mutation within the Proline-rich region of SHIP2 in Goto-Kakizaki (GK rats; a model for type 2 diabetes) and spontaneously hypertensive (SH-) rats. This mutation slightly impairs insulin signaling in cell culture (Marion et al., 2002).
Somatic In humans, a deletion in the SHIP2 3' untranslated region (UTR) has been identified in type 2 diabetic patients. In cell culture, this deletion enhances SHIP2 promoter activity in reporter assays and SHIP2 over-expression. This deletion is reported to be significantly associated with the presence of type 2 diabetes (Marion et al., 2002).

Implicated in

Entity Chronic myelogenous leukemia (CML)
Note SHIP2 is expressed at high levels in Bcr-Abl transformed K562 CML cells where it is highly tyrosine phosphorylated and constitutively associated with the adapter protein Shc in K562 leukemia cells (Wisniewski et al., 1999). Adenoviral-mediated exogenous overexpression of SHIP2 in K562 cells inhibits cell cycle progression (see 'Function - Cell cycle regulation' above).
Entity Breast cancer
Note SHIP2 is overexpressed in many breast cancer cells when compared to non-transformed mammary epithelial cells (Prasad et al., 2008). Stable SHIP2 RNA interference in MDA-231 and MDA-468 breast cancer cells decreases cell proliferation (Prasad et al., 2008; Prasad, 2009b). SHIP2 suppression also causes delayed tumorigenesis in nude mouse mammary fatpad xenograft studies (Prasad et al., 2008). SHIP2 overexpression is reported in clinical specimens of human breast cancers [n=65 (Prasad et al., 2008); and n=285 (Prasad et al., 2008)]. In invasive breast cancers (n=145), SHIP2 expression is positively correlated with reduced disease-free survival and estrogen receptor-negative (ER-) and EGF receptor-positive (EGFR+) status (Prasad et al., 2008).
Entity Hepatocellular carcinoma
Note SHIP2 expression in the cancer cells is decreased as compared to the adjacent normal cells of the same cancer specimens (n = 20) (Sumie et al., 2007). Any possible association between the SHIP2 levels and glucose intolerance or the aggressiveness of the disease remains to be examined.
Entity Type 2 diabetes
Note Single nucleotide polymorphisms (SNPs) in the SHIP2 gene promoter and the 5' untranlated region correlates with the impaired fasting glycemia in Japanese population (Ishida et al., 2006). The haplotypes found more frequently in glucose intolerant people increase transcription from SHIP2 promoter in reporter gene assays.
Evidence from transgenic animal studies in mouse showed that SHIP2 function in liver is important for insulin-dependent glucose homeostasis (Fukui et al., 2005; Buettner et al., 2007; Grempler et al., 2007; Kagawa et al., 2008).
Metabolic syndrome. Single nucleotide polymorphisms (SNPs) and haplotypes of SHIP2 are significantly correlated with symptoms of the metabolic syndrome including hypertension in British and French people from type 2 Diabetes families (Kaisaki et al., 2004). This association was not found with essential hypertension (not linked to metabolic syndrome) (Marcano et al., 2007).
Obesity. Evidence from gene knockout studies in mouse showed that SHIP2 deletion caused resistance to high-fat diet induced obesity (Sleeman et al., 2005) although insulin signaling was only mildly enhanced. These studies raised the possibility that global inhibition of SHIP2 will be tolerated (not lethal) without significant side-effects.


The inositol phosphatase SHIP-2 down-regulates FcgammaR-mediated phagocytosis in murine macrophages independently of SHIP-1.
Ai J, Maturu A, Johnson W, Wang Y, Marsh CB, Tridandapani S.
Blood. 2006 Jan 15;107(2):813-20. Epub 2005 Sep 22.
PMID 16179375
Catalytically inactive SHIP2 inhibits proliferation by attenuating PDGF signaling in 3T3-L1 preadipocytes.
Artemenko Y, Gagnon A, Sorisky A.
J Cell Physiol. 2009 Jan;218(1):228-36.
PMID 18814181
The inositol polyphosphate 5-phosphatases: traffic controllers, waistline watchers and tumour suppressors?
Astle MV, Horan KA, Ooms LM, Mitchell CA.
Biochem Soc Symp. 2007;(74):161-81. (REVIEW)
PMID 17233589
The control of phosphatidylinositol 3,4-bisphosphate concentrations by activation of the Src homology 2 domain containing inositol polyphosphate 5-phosphatase 2, SHIP2.
Batty IH, van der Kaay J, Gray A, Telfer JF, Dixon MJ, Downes CP.
Biochem J. 2007 Oct 15;407(2):255-66.
PMID 17672824
SHIP2: an emerging target for the treatment of type 2 diabetes mellitus.
Baumgartener JW.
Curr Drug Targets Immune Endocr Metabol Disord. 2003 Dec;3(4):291-8. (REVIEW)
PMID 14683460
Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.
Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD.
Nat Cell Biol. 2001 Nov;3(11):1014-9.
PMID 11715023
Antisense oligonucleotides against the lipid phosphatase SHIP2 improve muscle insulin sensitivity in a dietary rat model of the metabolic syndrome.
Buettner R, Ottinger I, Gerhardt-Salbert C, Wrede CE, Scholmerich J, Bollheimer LC.
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1871-8. Epub 2007 Feb 27.
PMID 17327370
Comparative mechanistic and substrate specificity study of inositol polyphosphate 5-phosphatase Schizosaccharomyces pombe Synaptojanin and SHIP2.
Chi Y, Zhou B, Wang WQ, Chung SK, Kwon YU, Ahn YH, Chang YT, Tsujishita Y, Hurley JH, Zhang ZY.
J Biol Chem. 2004 Oct 22;279(43):44987-95. Epub 2004 Aug 16.
PMID 15316017
PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells.
Choi Y, Zhang J, Murga C, Yu H, Koller E, Monia BP, Gutkind JS, Li W.
Oncogene. 2002 Aug 8;21(34):5289-300.
PMID 12149650
SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles.
Deleris P, Bacqueville D, Gayral S, Carrez L, Salles JP, Perret B, Breton-Douillon M.
J Biol Chem. 2003 Oct 3;278(40):38884-91. Epub 2003 Jul 7.
PMID 12847108
Metabolic switching of PI3K-dependent lipid signals.
Downes CP, Leslie NR, Batty IH, van der Kaay J.
Biochem Soc Trans. 2007 Apr;35(Pt 2):188-92.
PMID 17371235
The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
Dyson JM, Kong AM, Wiradjaja F, Astle MV, Gurung R, Mitchell CA.
Int J Biochem Cell Biol. 2005 Nov;37(11):2260-5. (REVIEW)
PMID 15964236
SHIP-2 forms a tetrameric complex with filamin, actin, and GPIb-IX-V: localization of SHIP-2 to the activated platelet actin cytoskeleton.
Dyson JM, Munday AD, Kong AM, Huysmans RD, Matzaris M, Layton MJ, Nandurkar HH, Berndt MC, Mitchell CA.
Blood. 2003 Aug 1;102(3):940-8. Epub 2003 Apr 3.
PMID 12676785
The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin.
Dyson JM, O'Malley CJ, Becanovic J, Munday AD, Berndt MC, Coghill ID, Nandurkar HH, Ooms LM, Mitchell CA.
J Cell Biol. 2001 Dec 10;155(6):1065-79. Epub 2001 Dec 10.
PMID 11739414
Impact of the liver-specific expression of SHIP2 (SH2-containing inositol 5'-phosphatase 2) on insulin signaling and glucose metabolism in mice.
Fukui K, Wada T, Kagawa S, Nagira K, Ikubo M, Ishihara H, Kobayashi M, Sasaoka T.
Diabetes. 2005 Jul;54(7):1958-67.
PMID 15983195
SH2-containing inositol 5-phosphatases 1 and 2 in blood platelets: their interactions and roles in the control of phosphatidylinositol 3,4,5-trisphosphate levels.
Giuriato S, Pesesse X, Bodin S, Sasaki T, Viala C, Marion E, Penninger J, Schurmans S, Erneux C, Payrastre B.
Biochem J. 2003 Nov 15;376(Pt 1):199-207.
PMID 12885297
Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
Grempler R, Zibrova D, Schoelch C, van Marle A, Rippmann JF, Redemann N.
Diabetes. 2007 Sep;56(9):2235-41. Epub 2007 Jun 27.
PMID 17596404
Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2 protein.
Habib T, Hejna JA, Moses RE, Decker SJ.
J Biol Chem. 1998 Jul 17;273(29):18605-9.
PMID 9660833
Cloning and characterization of a human cDNA (INPPL1) sharing homology with inositol polyphosphate phosphatases.
Hejna JA, Saito H, Merkens LS, Tittle TV, Jakobs PM, Whitney MA, Grompe M, Friedberg AS, Moses RE.
Genomics. 1995 Sep 1;29(1):285-7.
PMID 8530088
Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice.
Hori H, Sasaoka T, Ishihara H, Wada T, Murakami S, Ishiki M, Kobayashi M.
Diabetes. 2002 Aug;51(8):2387-94.
PMID 12145149
Transcriptional profiling of C2C12 myotubes in response to SHIP2 depletion and insulin stimulation.
Huard C, Martinez RV, Ross C, Johnson JW, Zhong W, Hill AA, Kim R, Paulsen JE, Shih HH.
Genomics. 2007 Feb;89(2):270-9. Epub 2006 Nov 21.
PMID 17123777
Association of SH-2 containing inositol 5'-phosphatase 2 gene polymorphisms and hyperglycemia.
Ishida S, Funakoshi A, Miyasaka K, Shimokata H, Ando F, Takiguchi S.
Pancreas. 2006 Jul;33(1):63-7.
PMID 16804414
Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice.
Kagawa S, Soeda Y, Ishihara H, Oya T, Sasahara M, Yaguchi S, Oshita R, Wada T, Tsuneki H, Sasaoka T.
Endocrinology. 2008 Feb;149(2):642-50. Epub 2007 Nov 26.
PMID 18039790
Polymorphisms in type II SH2 domain-containing inositol 5-phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic syndrome.
Kaisaki PJ, Delepine M, Woon PY, Sebag-Montefiore L, Wilder SP, Menzel S, Vionnet N, Marion E, Riveline JP, Charpentier G, Schurmans S, Levy JC, Lathrop M, Farrall M, Gauguier D.
Diabetes. 2004 Jul;53(7):1900-4.
PMID 15220217
The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading.
Koch A, Mancini A, El Bounkari O, Tamura T.
Oncogene. 2005 May 12;24(21):3436-47.
PMID 15735664
SHIPs ahoy.
Krystal G, Damen JE, Helgason CD, Huber M, Hughes MR, Kalesnikoff J, Lam V, Rosten P, Ware MD, Yew S, Humphries RK.
Int J Biochem Cell Biol. 1999 Oct;31(10):1007-10. (REVIEW)
PMID 10582334
Lipid phosphatases as drug discovery targets for type 2 diabetes.
Lazar DF, Saltiel AR.
Nat Rev Drug Discov. 2006 Apr;5(4):333-42. (REVIEW)
PMID 16582877
The inositol 5'-phosphatase SHIP-2 negatively regulates IgE-induced mast cell degranulation and cytokine production.
Leung WH, Bolland S.
J Immunol. 2007 Jul 1;179(1):95-102.
PMID 17579026
Genetic association analysis of inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) variants with essential hypertension.
Marcano AC, Burke B, Gungadoo J, Wallace C, Kaisaki PJ, Woon PY, Farrall M, Clayton D, Brown M, Dominiczak A, Connell JM, Webster J, Lathrop M, Caulfield M, Samani N, Gauguier D, Munroe PB.
J Med Genet. 2007 Sep;44(9):603-5. Epub 2007 Jun 8.
PMID 17557929
The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man.
Marion E, Kaisaki PJ, Pouillon V, Gueydan C, Levy JC, Bodson A, Krzentowski G, Daubresse JC, Mockel J, Behrends J, Servais G, Szpirer C, Kruys V, Gauguier D, Schurmans S.
Diabetes. 2002 Jul;51(7):2012-7.
PMID 12086927
The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice.
Muraille E, Dassesse D, Vanderwinden JM, Cremer H, Rogister B, Erneux C, Schiffmann SN.
Neuroscience. 2001;105(4):1019-30.
PMID 11530239
SHIP-2 inositol phosphatase is inducibly expressed in human monocytes and serves to regulate Fcgamma receptor-mediated signaling.
Pengal RA, Ganesan LP, Fang H, Marsh CB, Anderson CL, Tridandapani S.
J Biol Chem. 2003 Jun 20;278(25):22657-63. Epub 2003 Apr 10.
PMID 12690104
Identification of a second SH2-domain-containing protein closely related to the phosphatidylinositol polyphosphate 5-phosphatase SHIP.
Pesesse X, Deleu S, De Smedt F, Drayer L, Erneux C.
Biochem Biophys Res Commun. 1997 Oct 29;239(3):697-700.
PMID 9367831
The SH2 domain containing inositol 5-phosphatase SHIP2 displays phosphatidylinositol 3,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate 5-phosphatase activity.
Pesesse X, Moreau C, Drayer AL, Woscholski R, Parker P, Erneux C.
FEBS Lett. 1998 Oct 23;437(3):301-3.
PMID 9824312
Src family tyrosine kinases regulate adhesion-dependent tyrosine phosphorylation of 5'-inositol phosphatase SHIP2 during cell attachment and spreading on collagen I.
Prasad N, Topping RS, Decker SJ.
J Cell Sci. 2002 Oct 1;115(Pt 19):3807-15.
PMID 12235291
SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
Prasad NK, Decker SJ.
J Biol Chem. 2005 Apr 1;280(13):13129-36. Epub 2005 Jan 24.
PMID 15668240
High expression of obesity-linked phosphatase SHIP2 in invasive breast cancer correlates with reduced disease-free survival.
Prasad NK, Tandon M, Handa A, Moore GE, Babbs CF, Snyder PW, Bose S.
Tumour Biol. 2008;29(5):330-41. Epub 2008 Nov 15
PMID 19065064
SHIP2 phosphoinositol phosphatase positively regulates EGFR-Akt pathway, CXCR4 expression, and cell migration in MDA-MB-231 breast cancer cells.
Prasad NK.
Int J Oncol. 2009b Jan;34(1):97-105.
PMID 19082482
Structure, function, and biology of SHIP proteins.
Rohrschneider LR, Fuller JF, Wolf I, Liu Y, Lucas DM.
Genes Dev. 2000 Mar 1;14(5):505-20. (REVIEW)
PMID 10716940
Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways.
Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ.
Nat Cell Biol. 2001 Nov;3(11):1009-13.
PMID 11715022
Cultured peripheral blood mast cells from chronic idiopathic urticaria patients spontaneously degranulate upon IgE sensitization: Relationship to expression of Syk and SHIP-2.
Saini SS, Paterniti M, Vasagar K, Gibbons SP Jr, Sterba PM, Vonakis BM.
Clin Immunol. 2009 May 26. [Epub ahead of print]
PMID 19477690
SH2-containing inositol phosphatase 2 negatively regulates insulin-induced glycogen synthesis in L6 myotubes.
Sasaoka T, Hori H, Wada T, Ishiki M, Haruta T, Ishihara H, Kobayashi M.
Diabetologia. 2001 Oct;44(10):1258-67.
PMID 11692174
Lipid phosphatases as a possible therapeutic target in cases of type 2 diabetes and obesity.
Sasaoka T, Wada T, Tsuneki H.
Pharmacol Ther. 2006 Dec;112(3):799-809. Epub 2006 Jul 13. (REVIEW)
PMID 16842857
Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity.
Sleeman MW, Wortley KE, Lai KM, Gowen LC, Kintner J, Kline WO, Garcia K, Stitt TN, Yancopoulos GD, Wiegand SJ, Glass DJ.
Nat Med. 2005 Feb;11(2):199-205. Epub 2005 Jan 16.
PMID 15654325
Significance of glucose intolerance and SHIP2 expression in hepatocellular carcinoma patients with HCV infection.
Sumie S, Kawaguchi T, Komuta M, Kuromatsu R, Itano S, Okuda K, Taniguchi E, Ando E, Takata A, Fukushima N, Koga H, Torimura T, Kojiro M, Sata M.
Oncol Rep. 2007 Sep;18(3):545-52.
PMID 17671700
5' phospholipid phosphatase SHIP-2 causes protein kinase B inactivation and cell cycle arrest in glioblastoma cells.
Taylor V, Wong M, Brandts C, Reilly L, Dean NM, Cowsert LM, Moodie S, Stokoe D.
Mol Cell Biol. 2000 Sep;20(18):6860-71.
PMID 10958682
Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity.
Wada T, Sasaoka T, Funaki M, Hori H, Murakami S, Ishiki M, Haruta T, Asano T, Ogawa W, Ishihara H, Kobayashi M.
Mol Cell Biol. 2001 Mar;21(5):1633-46.
PMID 11238900
SHIP2 is recruited to the cell membrane upon macrophage colony-stimulating factor (M-CSF) stimulation and regulates M-CSF-induced signaling.
Wang Y, Keogh RJ, Hunter MG, Mitchell CA, Frey RS, Javaid K, Malik AB, Schurmans S, Tridandapani S, Marsh CB.
J Immunol. 2004 Dec 1;173(11):6820-30.
PMID 15557176
A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells.
Wisniewski D, Strife A, Swendeman S, Erdjument-Bromage H, Geromanos S, Kavanaugh WM, Tempst P, Clarkson B.
Blood. 1999 Apr 15;93(8):2707-20.
PMID 10194451
SHIP2 associates with intersectin and recruits it to the plasma membrane in response to EGF.
Xie J, Vandenbroere I, Pirson I.
FEBS Lett. 2008 Sep 3;582(20):3011-7. Epub 2008 Aug 8.
PMID 18692052
MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia.
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PMID 19033458
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PMID 15494023
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PMID 17135240


This paper should be referenced as such :
Prasad, NK
INPPL1 (inositol polyphosphate phosphatase-like 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(5):454-459.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)INPPL1   6080
Atlas Explorer : (Salamanque)INPPL1
Entrez_Gene (NCBI)INPPL1    inositol polyphosphate phosphatase like 1
GeneCards (Weizmann)INPPL1
Ensembl hg19 (Hinxton)ENSG00000165458 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000165458 [Gene_View]  ENSG00000165458 [Sequence]  chr11:72224767-72239144 [Contig_View]  INPPL1 [Vega]
ICGC DataPortalENSG00000165458
Genatlas (Paris)INPPL1
SOURCE (Princeton)INPPL1
Genetics Home Reference (NIH)INPPL1
Genomic and cartography
GoldenPath hg38 (UCSC)INPPL1  -     chr11:72224767-72239144 +  11q13.4   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)INPPL1  -     11q13.4   [Description]    (hg19-Feb_2009)
GoldenPathINPPL1 - 11q13.4 [CytoView hg19]  INPPL1 - 11q13.4 [CytoView hg38]
Genome Data Viewer NCBIINPPL1 [Mapview hg19]  
OMIM258480   600829   
Gene and transcription
Genbank (Entrez)BC140853 BG236320 L24444 L36818 Y14385
RefSeq transcript (Entrez)NM_001567
Consensus coding sequences : CCDS (NCBI)INPPL1
Gene ExpressionINPPL1 [ NCBI-GEO ]   INPPL1 [ EBI - ARRAY_EXPRESS ]   INPPL1 [ SEEK ]   INPPL1 [ MEM ]
Gene Expression Viewer (FireBrowse)INPPL1 [ Firebrowse - Broad ]
GenevisibleExpression of INPPL1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3636
GTEX Portal (Tissue expression)INPPL1
Human Protein AtlasENSG00000165458-INPPL1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15357   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO15357  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO15357
Domaine pattern : Prosite (Expaxy)SAM_DOMAIN (PS50105)    SH2 (PS50001)   
Domains : Interpro (EBI)Endo/exonu/phosph_ase_sf    Endo/exonuclease/phosphatase    IPPc    SAM    SAM/pointed_sf    SH2    SH2_dom_sf   
Domain families : Pfam (Sanger)Exo_endo_phos (PF03372)    SAM_1 (PF00536)    SH2 (PF00017)   
Domain families : Pfam (NCBI)pfam03372    pfam00536    pfam00017   
Domain families : Smart (EMBL)IPPc (SM00128)  SAM (SM00454)  SH2 (SM00252)  
Conserved Domain (NCBI)INPPL1
PDB (RSDB)2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
PDB Europe2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
PDB (PDBSum)2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
PDB (IMB)2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
Structural Biology KnowledgeBase2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
SCOP (Structural Classification of Proteins)2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
CATH (Classification of proteins structures)2K4P    2KSO    2MK2    3NR8    4A9C    5OKM    5OKN    5OKO    5OKP   
AlphaFold pdb e-kbO15357   
Human Protein Atlas [tissue]ENSG00000165458-INPPL1 [tissue]
Protein Interaction databases
IntAct (EBI)O15357
Ontologies - Pathways
Ontology : AmiGOendochondral ossification  immune system process  actin binding  protein binding  nucleus  Golgi apparatus  cytosol  cytosol  cytoskeleton  plasma membrane  glucose metabolic process  phosphatidylinositol biosynthetic process  endocytosis  actin filament organization  cell adhesion  negative regulation of cell population proliferation  post-embryonic development  negative regulation of gene expression  nuclear speck  SH3 domain binding  lamellipodium  filopodium  response to insulin  phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity  SH2 domain binding  phosphatidylinositol dephosphorylation  ruffle assembly  
Ontology : EGO-EBIendochondral ossification  immune system process  actin binding  protein binding  nucleus  Golgi apparatus  cytosol  cytosol  cytoskeleton  plasma membrane  glucose metabolic process  phosphatidylinositol biosynthetic process  endocytosis  actin filament organization  cell adhesion  negative regulation of cell population proliferation  post-embryonic development  negative regulation of gene expression  nuclear speck  SH3 domain binding  lamellipodium  filopodium  response to insulin  phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity  SH2 domain binding  phosphatidylinositol dephosphorylation  ruffle assembly  
REACTOMEO15357 [protein]
REACTOME PathwaysR-HSA-912526 [pathway]   
NDEx NetworkINPPL1
Atlas of Cancer Signalling NetworkINPPL1
Wikipedia pathwaysINPPL1
Orthology - Evolution
GeneTree (enSembl)ENSG00000165458
Phylogenetic Trees/Animal Genes : TreeFamINPPL1
Homologs : HomoloGeneINPPL1
Homology/Alignments : Family Browser (UCSC)INPPL1
Gene fusions - Rearrangements
Fusion : FusionGDB3.1.3.86   
Fusion : FusionHubCTTN--INPPL1    FN1--INPPL1    INPPL1--CD2BP2    INPPL1--COIL    INPPL1--GAB2    INPPL1--INPPL1    INPPL1--NPM1    INPPL1--TNNT3    INPPL1--UBA1    NDUFS5--INPPL1   
Fusion : QuiverINPPL1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerINPPL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)INPPL1
Exome Variant ServerINPPL1
GNOMAD BrowserENSG00000165458
Varsome BrowserINPPL1
ACMGINPPL1 variants
Genomic Variants (DGV)INPPL1 [DGVbeta]
DECIPHERINPPL1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisINPPL1 
ICGC Data PortalINPPL1 
TCGA Data PortalINPPL1 
Broad Tumor PortalINPPL1
OASIS PortalINPPL1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICINPPL1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DINPPL1
Mutations and Diseases : HGMDINPPL1
intOGen PortalINPPL1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)INPPL1
DoCM (Curated mutations)INPPL1
CIViC (Clinical Interpretations of Variants in Cancer)INPPL1
NCG (London)INPPL1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM258480    600829   
Orphanet553    2813   
Genetic Testing Registry INPPL1
NextProtO15357 [Medical]
Target ValidationINPPL1
Huge Navigator INPPL1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDINPPL1
Pharm GKB GenePA29888
Clinical trialINPPL1
DataMed IndexINPPL1
Other database
PubMed144 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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