Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001437
UniProt IDQ92835
Primary gene name(s)INPP5D
Synonym gene name(s)SHIP, SHIP1
Protein namePhosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
Protein functionPhosphatidylinositol, PtdIns phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate, PtdIns(3,4,5P3 to produce PtdIns(3,4P2, thereby negatively regulating the PI3K, phosphoinositide 3-kinase pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor, FCGR2B, playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. {ECO:0000269|PubMed:12421919, ECO:0000269|PubMed:16682172}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:10822173}. Cell membrane {ECO:0000250|UniProtKB:Q9ES52};
Peripheral membrane protein {ECO:0000250|UniProtKB:Q9ES52}. Membrane raft {ECO:0000250|UniProtKB:Q9ES52}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9ES52}. Membrane {ECO:0000269|PubMed:10822173};
Peripheral membrane protein {ECO:0000269|PubMed:10822173}. Note=Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Translocates from the cytoplasm to membrane ruffles in a FCGR3/CD16-dependent manner. Colocalizes with FC-gamma-RIIB receptor, FCGR2B or FCGR3/CD16 at membrane ruffles. Tyrosine phosphorylation may also participate in membrane localization. {ECO:0000250|UniProtKB:Q9ES52}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q92835
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
determination of adult lifespan [GO:0008340];
immunoglobulin mediated immune response [GO:0016064];
inositol phosphate metabolic process [GO:0043647];
intracellular signal transduction [GO:0035556];
leukocyte migration [GO:0050900];
negative regulation of B cell proliferation [GO:0030889];
negative regulation of bone resorption [GO:0045779];
negative regulation of immune response [GO:0050777];
negative regulation of interleukin-6 biosynthetic process [GO:0045409];
negative regulation of monocyte differentiation [GO:0045656];
negative regulation of neutrophil differentiation [GO:0045659];
negative regulation of osteoclast differentiation [GO:0045671];
negative regulation of signal transduction [GO:0009968];
phosphate-containing compound metabolic process [GO:0006796];
phosphatidylinositol biosynthetic process [GO:0006661];
phosphatidylinositol dephosphorylation [GO:0046856];
positive regulation of apoptotic process [GO:0043065];
positive regulation of B cell differentiation [GO:0045579];
positive regulation of erythrocyte differentiation [GO:0045648];
signal transduction [GO:0007165];
T cell receptor signaling pathway [GO:0050852]
Gene Ontology
(Molecular Function)
Complete annatation
inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity [GO:0052659];
inositol-polyphosphate 5-phosphatase activity [GO:0004445];
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity [GO:0016314];
phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity [GO:0034485]
Gene Ontology
(Cellular Component)
Complete annatation
cytoskeleton [GO:0005856];
cytosol [GO:0005829];
membrane raft [GO:0045121];
plasma membrane [GO:0005886]
Protein-protein interaction109847
Phylogenetic treeQ92835
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-1.918243083752630.0003543616547321270.00146729089563808
AZA vs. DISU-0.06048906062817640.811409962974220.983626273983733
AZA vs. IL7-0.09413675193329310.6243771029759660.999311006273513
AZA vs. SAHA-0.2768186580220740.2570008575350610.629514287696378
DISU vs. CD31.846083105796840.0006497225901527240.00284872551598667
DISU vs. IL7-0.04328966656940030.8634361949700860.974062989549638
DISU vs. SAHA-0.214263680596450.4618995496517760.800119649301005
DMSO vs. AZA0.02925858974103350.8611552460652481
DMSO vs. CD31.936162567421370.0002663262435976810.00107163591340787
DMSO vs. DISU0.08793019358341960.7186517212743820.963064442066846
DMSO vs. IL7-0.1160776160394080.518110404777270.889301967358611
DMSO vs. SAHA-0.311697344271230.1861481751242960.521105719310616
HIV vs. Mock in Activation0.4594899863815710.6775382496538030.999983755607037
HIV vs. Mock in Latency0.08421766395670630.6090235026273070.999834320637052
IL7 vs. CD31.829896429335290.0005181511301486360.00241574141191785
SAHA vs. CD31.617859582119940.002273832139135790.00723230273042979
SAHA vs. IL7-0.1851556732147010.4466282116846980.685464259131425
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.0573689 0.743479
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.02 1.041 1.031 1.169 1.126
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2YSX NMR - A=1-112.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 upregulates 24162774

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00562 Inositol phosphate metabolism - Homo sapiens (human)
hsa04070 Phosphatidylinositol signaling system - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)