Inppl1 inositol polyphosphate phosphatase-like 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Inppl1provided by MGI
Official Full Name: inositol polyphosphate phosphatase-like 1provided by MGI
Primary source: MGI:MGI:1333787
See related: Ensembl:ENSMUSG00000032737 AllianceGenome:MGI:1333787
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: 51C; SHIP2
Summary: Predicted to enable SH2 domain binding activity; inositol-polyphosphate 5-phosphatase activity; and phosphatidylinositol-3,4,5-trisphosphate binding activity. Acts upstream of or within several processes, including intracellular signaling cassette; response to insulin; and ruffle assembly. Located in cytoplasm and plasma membrane. Is expressed in several structures, including alimentary system; brain; ear; respiratory system; and testis. Human ortholog(s) of this gene implicated in hypertension; obesity; and type 2 diabetes mellitus. Orthologous to human INPPL1 (inositol polyphosphate phosphatase like 1). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in ovary adult (RPKM 43.9), heart adult (RPKM 33.8) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7 E2; 7 54.67 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (101471839..101487419, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (101822632..101838226, complement)

Chromosome 7 - NC_000073.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The 5-Phosphatase SHIP2 Promotes Neutrophil Chemotaxis and Recruitment.
Title: The 5-Phosphatase SHIP2 Promotes Neutrophil Chemotaxis and Recruitment.
Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia.
Title: Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia.
The data suggest that inhibition of the catalytic activity of SHIP2 is beneficial in reducing oxidative stress, but leads to deleterious increase in apoptosis in podocytes with reduced expression of CD2AP.
Title: Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis.
Here, the authors systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern.
Title: Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions.
Inactivation of SHIP2 leads to increased microvilli formation and solute reabsorption by the renal proximal tubule and was associated with hyperactivated ezrin/radixin/moesin proteins and increased Rho-GTP.
Title: The lipid 5-phoshatase SHIP2 controls renal brush border ultrastructure and function by regulating the activation of ERM proteins.
data suggest that endothelial SHIP2 is required to maintain normal systemic glucose homeostasis and prevent oxidative stress-induced endothelial dysfunction.
Title: Endothelial SHIP2 Suppresses Nox2 NADPH Oxidase-Dependent Vascular Oxidative Stress, Endothelial Dysfunction, and Systemic Insulin Resistance.
The authors concluded that the FcgammaRIIb-SHIP2 axis links Abeta neurotoxicity to tau pathology by dysregulating phosphoinositide metabolism, providing insight into therapeutic potential against Alzheimer's disease.
Title: FcγRIIb-SHIP2 axis links Aβ to tau pathology by disrupting phosphoinositide metabolism in Alzheimer's disease model.
These findings suggest that palmitate contributes to SHIP2 overexpression in skeletal muscle via the mechanisms involving the activation of ceramide-JNK and NF-kappaB pathways.
Title: Palmitate induces SHIP2 expression via the ceramide-mediated activation of NF-κB, and JNK in skeletal muscle cells.
results suggest that SHIP2 contributes to the regulation of food intake mainly via the attenuation of insulin signalling in the hypothalamus of mice
Title: SH2-containing inositol 5'-phosphatase 2 selectively impairs hypothalamic insulin signalling and regulation of food intake in mice.
The catalytically-inactive Ship2 mutant protein in a context of reduced PtdIns(4,5)P2 3-kinase activity.
Title: Developmental defects and rescue from glucose intolerance of a catalytically-inactive novel Ship2 mutant mouse.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Inppl1 (e-PCR), detects polymorphism
- UniSTS:526217

Inppl1 (e-PCR), detects polymorphism
- UniSTS:526218

X75014 (e-PCR)
- UniSTS:125839

NoName (e-PCR)
- UniSTS:235730

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables SH2 domain binding	IEA Inferred from Electronic Annotation more info
enables SH2 domain binding	ISO Inferred from Sequence Orthology more info
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables actin binding	IEA Inferred from Electronic Annotation more info
enables inositol-polyphosphate 5-phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables inositol-polyphosphate 5-phosphatase activity	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3,4,5-trisphosphate binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within ERK1 and ERK2 cascade	IGI Inferred from Genetic Interaction more info	PubMed
involved_in actin filament organization	IEA Inferred from Electronic Annotation more info
involved_in actin filament organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within apoptotic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in endochondral ossification	ISO Inferred from Sequence Orthology more info
involved_in endochondral ossification	ISS Inferred from Sequence or Structural Similarity more info
involved_in endocytosis	IEA Inferred from Electronic Annotation more info
involved_in endocytosis	ISO Inferred from Sequence Orthology more info
involved_in establishment of mitotic spindle orientation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within gene expression	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within glucose metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune system process	IEA Inferred from Electronic Annotation more info
involved_in inositol trisphosphate metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA replication	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of insulin-like growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of insulin-like growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron projection development	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of platelet-derived growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within phosphatidylinositol biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphatidylinositol dephosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within post-embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of actin filament organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of protein localization	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within response to insulin	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ruffle assembly	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in basal plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in filopodium	IEA Inferred from Electronic Annotation more info
located_in lamellipodium	IEA Inferred from Electronic Annotation more info
located_in lamellipodium	ISO Inferred from Sequence Orthology more info
located_in nuclear speck	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in spindle pole	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2

Names: INPPL-1; SH2 domain-containing inositol 5'-phosphatase 2; SH2 domain-containing inositol phosphatase 2; SHIP-2; ablSH3-binding protein; inositol polyphosphate phosphatase-like protein 1; protein 51C

NP_001116211.1

EC 3.1.3.86

NP_001399517.1

EC 3.1.3.86

NP_001399518.1

EC 3.1.3.86

NP_001399519.1

EC 3.1.3.86

NP_001399520.1

EC 3.1.3.86

NP_034697.2

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.

mRNA and Protein(s)

NM_001122739.2 → NP_001116211.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform a

See identical proteins and their annotated locations for NP_001116211.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1-5 all encode the same isoform (a).

Source sequence(s)

AC159005

Consensus CDS

CCDS21515.1

UniProtKB/Swiss-Prot

O08611, Q0VDX5, Q6P549, Q80YB9, Q9JLL7

UniProtKB/TrEMBL

A0A087WPT7

Related

ENSMUSP00000132883.2, ENSMUST00000165052.8

Conserved Domains (3) summary

cd09491
Location:1193 → 1255

SAM_Ship2; SAM domain of Ship2 lipid phosphatase proteins

cd09101
Location:425 → 728

INPP5c_SHIP2-INPPL1; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol 5-phosphatase-2 and related proteins

cd10343
Location:17 → 119

SH2_SHIP; Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP)
NM_001412588.1 → NP_001399517.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform a

Status: VALIDATED

Source sequence(s)

AC159005

UniProtKB/Swiss-Prot

O08611, Q0VDX5, Q6P549, Q80YB9, Q9JLL7

UniProtKB/TrEMBL

A0A087WPT7
NM_001412589.1 → NP_001399518.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform a

Status: VALIDATED

Source sequence(s)

AC159005

UniProtKB/Swiss-Prot

O08611, Q0VDX5, Q6P549, Q80YB9, Q9JLL7

UniProtKB/TrEMBL

A0A087WPT7
NM_001412590.1 → NP_001399519.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform a

Status: VALIDATED

Source sequence(s)

AC159005

UniProtKB/Swiss-Prot

O08611, Q0VDX5, Q6P549, Q80YB9, Q9JLL7

UniProtKB/TrEMBL

A0A087WPT7
NM_001412591.1 → NP_001399520.1 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform b

Status: VALIDATED

Source sequence(s)

AC159005

UniProtKB/TrEMBL

A0A087WPT7

Related

ENSMUSP00000139910.2, ENSMUST00000185929.2
NM_010567.3 → NP_034697.2 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform a

See identical proteins and their annotated locations for NP_034697.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (a). Variants 1-5 all encode the same isoform (a).

Source sequence(s)

AC159005

Consensus CDS

CCDS21515.1

UniProtKB/Swiss-Prot

O08611, Q0VDX5, Q6P549, Q80YB9, Q9JLL7

UniProtKB/TrEMBL

A0A087WPT7

Related

ENSMUSP00000048057.7, ENSMUST00000035836.14

Conserved Domains (3) summary

cd09491
Location:1193 → 1255

SAM_Ship2; SAM domain of Ship2 lipid phosphatase proteins

cd09101
Location:425 → 728

INPP5c_SHIP2-INPPL1; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol 5-phosphatase-2 and related proteins

cd10343
Location:17 → 119

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