INPP5D inositol polyphosphate-5-phosphatase D [Homo sapiens (human)] - Gene

Summary

Official Symbol: INPP5Dprovided by HGNC
Official Full Name: inositol polyphosphate-5-phosphatase Dprovided by HGNC
Primary source: HGNC:HGNC:6079
See related: Ensembl:ENSG00000168918 MIM:601582; AllianceGenome:HGNC:6079
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SHIP; SHIP1; SHIP-1; hp51CN; SIP-145; p150Ship
Summary: This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Deficiencies in the encoded protein, SHIP1, have been associated with Inflammatory Bowel Disease types such as Crohn's Disease and Ulcerative Colitis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2020]
Expression: Broad expression in lymph node (RPKM 33.2), spleen (RPKM 31.1) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q37.1

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (233060342..233207903)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (233547692..233695995)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (233925052..234116549)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Potentially functional variants of INPP5D and EXOSC3 in immunity B cell-related genes are associated with non-small cell lung cancer survival.
Title: Potentially functional variants of INPP5D and EXOSC3 in immunity B cell-related genes are associated with non-small cell lung cancer survival.
SHIP inhibition mediates select TREM2-induced microglial functions.
Title: SHIP inhibition mediates select TREM2-induced microglial functions.
Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2.
Title: Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2.
INPP5D regulates inflammasome activation in human microglia.
Title: INPP5D regulates inflammasome activation in human microglia.
INPP5D/SHIP1: Expression, Regulation and Roles in Alzheimer's Disease Pathophysiology.
Title: INPP5D/SHIP1: Expression, Regulation and Roles in Alzheimer's Disease Pathophysiology.
Expression of INPP5D Isoforms in Human Brain: Impact of Alzheimer's Disease Neuropathology and Genetics.
Title: Expression of INPP5D Isoforms in Human Brain: Impact of Alzheimer's Disease Neuropathology and Genetics.
Targeted hyperactivation of AKT through inhibition of ectopic expressed SHIP1 induces cell death in colon carcinoma cells and derived metastases.
Title: Targeted hyperactivation of AKT through inhibition of ectopic expressed SHIP1 induces cell death in colon carcinoma cells and derived metastases.
Activated Src kinases downstream of BCR-ABL and Flt3 induces proteasomal degradation of SHIP1 by phosphorylation of tyrosine 1021.
Title: Activated Src kinases downstream of BCR-ABL and Flt3 induces proteasomal degradation of SHIP1 by phosphorylation of tyrosine 1021.
Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.
Title: Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.
CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression.
Title: CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression.

Submit: New GeneRIF Correction See all GeneRIFs (79)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of inositol polyphosphate-5-phosphatase, 145kDa (INPP5D) in human B cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G29434 (e-PCR)
- UniSTS:10754

SHGC-148855 (e-PCR)
- UniSTS:176648

SHGC-148856 (e-PCR)
- UniSTS:176649

D11S2921 (e-PCR)
- UniSTS:152074

SHGC-142327 (e-PCR)
- UniSTS:171392

INPP5D_160 (e-PCR)
- UniSTS:277386

D2S1279 (e-PCR), detects polymorphism
- UniSTS:149411

RH68049 (e-PCR)
- UniSTS:63658

GDB:335751 (e-PCR)
- UniSTS:156601

SHGC-61987 (e-PCR)
- UniSTS:39880

RH68337 (e-PCR)
- UniSTS:6352

AFMa053wc5 (e-PCR)
- UniSTS:35804

RH70363 (e-PCR)
- UniSTS:47598

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables inositol-polyphosphate 5-phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity	TAS Traceable Author Statement more info
enables phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity	TAS Traceable Author Statement more info
enables phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in determination of adult lifespan	IEA Inferred from Electronic Annotation more info
involved_in immunoglobulin mediated immune response	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of bone resorption	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of monocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neutrophil differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphate-containing compound metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in phosphatidylinositol biosynthetic process	TAS Traceable Author Statement more info
involved_in phosphatidylinositol dephosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of B cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane raft	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1

Names: SH2 domain-containing inositol 5'-phosphatase 1; inositol polyphosphate-5-phosphatase, 145kD; inositol polyphosphate-5-phosphatase, 145kDa; phosphatidylinositol 4,5-bisphosphate 5-phosphatase; signaling inositol polyphosphate 5 phosphatase SIP-145; signaling inositol polyphosphate phosphatase SHIP II

NP_001017915.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

NP_005532.2

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

XP_047300175.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

XP_047300176.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

XP_054187655.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

XP_054187656.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

XP_054197847.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

XP_054197848.1

EC 3.1.3.36

EC 3.1.3.56

EC 3.1.3.86

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033988.1 RefSeqGene

Range

5376..152937

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001017915.3 → NP_001017915.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform a

See identical proteins and their annotated locations for NP_001017915.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AW503130, BC099920, U53470

Consensus CDS

CCDS74672.1

UniProtKB/Swiss-Prot

O00145, Q13544, Q13545, Q6P5A4, Q92656, Q92835, Q9UE80

Related

ENSP00000405338.2, ENST00000445964.6

Conserved Domains (3) summary

cd09100
Location:404 → 710

INPP5c_SHIP1-INPP5D; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and related proteins

cd10343
Location:1 → 102

SH2_SHIP; Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP)

PHA03307
Location:899 → 1127

PHA03307; transcriptional regulator ICP4; Provisional
NM_005541.5 → NP_005532.2 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform b

See identical proteins and their annotated locations for NP_005532.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in an isoform (b) that is 1 aa shorter than isoform a.

Source sequence(s)

AW503130, BC099920, X98429

Consensus CDS

CCDS77543.1

UniProtKB/Swiss-Prot

Q92835

Related

ENSP00000352575.7, ENST00000359570.9

Conserved Domains (2) summary

cd09100
Location:403 → 709

INPP5c_SHIP1-INPP5D; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and related proteins

cd10343
Location:1 → 102

SH2_SHIP; Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

233060342..233207903

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047444219.1 → XP_047300175.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform X1
XM_047444220.1 → XP_047300176.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform X2

Reference GRCh38.p14 PATCHES

Genomic

NW_011332690.1 Reference GRCh38.p14 PATCHES

Range

5680..153241

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054331680.1 → XP_054187655.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform X1
XM_054331681.1 → XP_054187656.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

233547692..233695995

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054341872.1 → XP_054197847.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform X1
XM_054341873.1 → XP_054197848.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform X2