SHIP2 Antibody [D4N9] | Primary Antibodies

Application: Reactivity: Human, Mouse, Rat

Usage Information

Dilution
WB1:1000 - 1:10000 IHC1:100 - 1:250 IF1:100 - 1:250

Application
WB, IHC, IF

Reactivity
Human, Mouse, Rat

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW Observed MW
139 kDa 120-150 kDa
^*Why do the predicted and actual molecular weights differ? The following reasons may explain differences between the predicted and actual protein molecular weight. Post-translational modifications(e.g., phosphorylation, glycosylation); Splice variants and isoforms; Relative charge; Multimerization.

Datasheet & SDS

Biological Description

Specificity
SHIP2 Antibody [D4N9] detects endogenous levels of total SHIP2 protein.

Clone
D4N9

Synonym(s)
SHIP2, INPPL1, Inositol polyphosphate phosphatase-like protein 1, Protein 51C, SH2 domain-containing inositol 5'-phosphatase 2, INPPL-1, SH2 domain-containing inositol phosphatase 2, SHIP-2

Background
SHIP2 (INPPL1) is an SH2-domain–containing inositol 5‑phosphatase that hydrolyzes the 5‑phosphate of phosphatidylinositol‑3,4,5‑trisphosphate to generate phosphatidylinositol‑3,4‑bisphosphate, positioning it as a lipid phosphatase that dampens PI3K‑dependent signaling downstream of receptor tyrosine kinases and insulin receptors in metabolically active tissues. The protein contains an N‑terminal SH2 domain that targets SHIP2 to phosphotyrosine‑containing motifs on activated receptors and adaptors, a central catalytic 5‑phosphatase domain responsible for PIP3 dephosphorylation, and C‑terminal proline‑rich regions that mediate interactions with scaffolds and components of endocytic machinery, which allows SHIP2 to integrate both signaling and trafficking functions at the plasma membrane. Genetic disruption in mice shows that loss of SHIP2 increases insulin sensitivity and glucose uptake: SHIP2‑null neonates display severe hypoglycemia and deregulated expression of gluconeogenic genes, and adult heterozygotes exhibit enhanced recruitment of GLUT4 and increased glycogen synthesis in skeletal muscle, consistent with sustained PIP3 levels, augmented Akt phosphorylation, and amplified insulin signal transduction. Liver‑specific inhibition of SHIP2 in hyperglycemic, hyperinsulinemic KKAy mice elevates basal and insulin‑stimulated Akt phosphorylation, reduces expression of glucose‑6‑phosphatase and phosphoenolpyruvate carboxykinase, decreases hepatic gluconeogenesis, and shifts glycogen phosphorylase and glycogen synthase phosphorylation states to favor glycogen accumulation; these changes are accompanied by improved glycolysis, higher hepatic glycogen content, and marked reductions in prandial blood glucose, demonstrating that SHIP2 restrains insulin’s metabolic actions at the level of hepatocyte PIP3 turnover. Across models of diet‑induced obesity and insulin resistance, SHIP2 expression and activity are elevated, and correlate with impaired PI3K–Akt signaling, and pharmacologic SHIP2 inhibition or genetic knockdown exerts insulin‑mimetic effects on glucose metabolism and GLUT1/GLUT4 expression, placing this phosphatase as a central negative regulator of insulin pathway amplitude and a candidate therapeutic target in type 2 diabetes and related metabolic disorders. SHIP2 also modulates FGF‑driven MAPK outputs and receptor tyrosine kinase pathways in vivo, with zebrafish and mammalian data showing that Ship2 attenuates FGF‑dependent gene expression and ERK activation during embryonic patterning, indicating broader roles in RTK signaling beyond metabolic control. Endothelial‑specific manipulation of SHIP2 reveals additional vascular functions: reduced endothelial SHIP2 alters insulin‑stimulated glucose uptake in peripheral tissues and impacts Nox2‑dependent oxidative stress and endothelial dysfunction, linking PI3K lipid phosphatase activity in the endothelium to systemic glucose homeostasis and vascular health.

Background

SHIP2 (INPPL1) is an SH2-domain–containing inositol 5‑phosphatase that hydrolyzes the 5‑phosphate of phosphatidylinositol‑3,4,5‑trisphosphate to generate phosphatidylinositol‑3,4‑bisphosphate, positioning it as a lipid phosphatase that dampens PI3K‑dependent signaling downstream of receptor tyrosine kinases and insulin receptors in metabolically active tissues. The protein contains an N‑terminal SH2 domain that targets SHIP2 to phosphotyrosine‑containing motifs on activated receptors and adaptors, a central catalytic 5‑phosphatase domain responsible for PIP3 dephosphorylation, and C‑terminal proline‑rich regions that mediate interactions with scaffolds and components of endocytic machinery, which allows SHIP2 to integrate both signaling and trafficking functions at the plasma membrane. Genetic disruption in mice shows that loss of SHIP2 increases insulin sensitivity and glucose uptake: SHIP2‑null neonates display severe hypoglycemia and deregulated expression of gluconeogenic genes, and adult heterozygotes exhibit enhanced recruitment of GLUT4 and increased glycogen synthesis in skeletal muscle, consistent with sustained PIP3 levels, augmented Akt phosphorylation, and amplified insulin signal transduction. Liver‑specific inhibition of SHIP2 in hyperglycemic, hyperinsulinemic KKAy mice elevates basal and insulin‑stimulated Akt phosphorylation, reduces expression of glucose‑6‑phosphatase and phosphoenolpyruvate carboxykinase, decreases hepatic gluconeogenesis, and shifts glycogen phosphorylase and glycogen synthase phosphorylation states to favor glycogen accumulation; these changes are accompanied by improved glycolysis, higher hepatic glycogen content, and marked reductions in prandial blood glucose, demonstrating that SHIP2 restrains insulin’s metabolic actions at the level of hepatocyte PIP3 turnover. Across models of diet‑induced obesity and insulin resistance, SHIP2 expression and activity are elevated, and correlate with impaired PI3K–Akt signaling, and pharmacologic SHIP2 inhibition or genetic knockdown exerts insulin‑mimetic effects on glucose metabolism and GLUT1/GLUT4 expression, placing this phosphatase as a central negative regulator of insulin pathway amplitude and a candidate therapeutic target in type 2 diabetes and related metabolic disorders. SHIP2 also modulates FGF‑driven MAPK outputs and receptor tyrosine kinase pathways in vivo, with zebrafish and mammalian data showing that Ship2 attenuates FGF‑dependent gene expression and ERK activation during embryonic patterning, indicating broader roles in RTK signaling beyond metabolic control. Endothelial‑specific manipulation of SHIP2 reveals additional vascular functions: reduced endothelial SHIP2 alters insulin‑stimulated glucose uptake in peripheral tissues and impacts Nox2‑dependent oxidative stress and endothelial dysfunction, linking PI3K lipid phosphatase activity in the endothelium to systemic glucose homeostasis and vascular health.

References
https://pubmed.ncbi.nlm.nih.gov/11343120/ https://pubmed.ncbi.nlm.nih.gov/17596404/

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%