TISIDB

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
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.
Domain	PF03372 Endonuclease/Exonuclease/phosphatase family PF00536 SAM domain (Sterile alpha motif) PF00017 SH2 domain
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 (PubMed:21624956). 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.

> Gene Ontology [ TOP ]
Biological Process	GO:0001501 skeletal system development GO:0001503 ossification GO:0001958 endochondral ossification GO:0005996 monosaccharide metabolic process GO:0006006 glucose metabolic process GO:0006066 alcohol metabolic process GO:0006644 phospholipid metabolic process GO:0006650 glycerophospholipid metabolic process GO:0006661 phosphatidylinositol biosynthetic process GO:0007015 actin filament organization GO:0008654 phospholipid biosynthetic process GO:0009791 post-embryonic development GO:0016311 dephosphorylation GO:0019318 hexose metabolic process GO:0019751 polyol metabolic process GO:0030031 cell projection assembly GO:0030258 lipid modification GO:0031529 ruffle organization GO:0032868 response to insulin GO:0036075 replacement ossification GO:0043434 response to peptide hormone GO:0043647 inositol phosphate metabolic process GO:0044723 single-organism carbohydrate metabolic process GO:0045017 glycerolipid biosynthetic process GO:0046474 glycerophospholipid biosynthetic process GO:0046486 glycerolipid metabolic process GO:0046488 phosphatidylinositol metabolic process GO:0046839 phospholipid dephosphorylation GO:0046856 phosphatidylinositol dephosphorylation GO:0048705 skeletal system morphogenesis GO:0060348 bone development GO:0060349 bone morphogenesis GO:0060350 endochondral bone morphogenesis GO:0097178 ruffle assembly GO:1901615 organic hydroxy compound metabolic process GO:1901652 response to peptide
Molecular Function	GO:0003779 actin binding GO:0016791 phosphatase activity GO:0017124 SH3 domain binding GO:0034485 phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity GO:0034594 phosphatidylinositol trisphosphate phosphatase activity GO:0034595 phosphatidylinositol phosphate 5-phosphatase activity GO:0042169 SH2 domain binding GO:0042578 phosphoric ester hydrolase activity GO:0052659 inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity GO:0052743 inositol tetrakisphosphate phosphatase activity GO:0052745 inositol phosphate phosphatase activity GO:0052866 phosphatidylinositol phosphate phosphatase activity
Cellular Component	GO:0030027 lamellipodium GO:0030175 filopodium GO:0031252 cell leading edge GO:0098858 actin-based cell projection

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04070 Phosphatidylinositol signaling system hsa04662 B cell receptor signaling pathway hsa04666 Fc gamma R-mediated phagocytosis hsa04910 Insulin signaling pathway hsa00562 Inositol phosphate metabolism
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-1483249: Inositol phosphate metabolism R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-1483255: PI Metabolism R-HSA-1483257: Phospholipid metabolism R-HSA-449147: Signaling by Interleukins R-HSA-1855204: Synthesis of IP3 and IP4 in the cytosol R-HSA-1660499: Synthesis of PIPs at the plasma membrane

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04070 Phosphatidylinositol signaling system
hsa04662 B cell receptor signaling pathway
hsa04666 Fc gamma R-mediated phagocytosis
hsa04910 Insulin signaling pathway
hsa00562 Inositol phosphate metabolism

Reactome

R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-1483249: Inositol phosphate metabolism
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1483255: PI Metabolism
R-HSA-1483257: Phospholipid metabolism
R-HSA-449147: Signaling by Interleukins
R-HSA-1855204: Synthesis of IP3 and IP4 in the cytosol
R-HSA-1660499: Synthesis of PIPs at the plasma membrane

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between INPPL1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of INPPL1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of INPPL1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.11	0.588
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.111	0.958
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.115	0.944
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.209	0.487
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.296	0.912
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.105	0.976
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.078	0.847
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.082	0.965
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.114	0.955
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.892	0.636
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.353	0.621
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.065	0.287

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of INPPL1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	0	11.1	0.0181
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	0	11.1	0.0286
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	10.5	0	10.5	0.135
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of INPPL1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of INPPL1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by INPPL1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of INPPL1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of INPPL1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between INPPL1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	INPPL1
Name	inositol polyphosphate phosphatase-like 1
Aliases	SHIP2; 51C protein; SH2 domain-containing inositol 5'-phosphatase 2; OPSMD; INPPL-1; SH2 domain-containing i ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting INPPL1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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