SPHINGOSINE-1-PHOSPHATE PHOSPHATASE 2; SGPP2

Alternative titles; symbols

• SPHINGOSINE-1-PHOSPHATE PHOSPHOHYDROLASE 2; SPP2

HGNC Approved Gene Symbol: SGPP2

Cytogenetic location: 2q36.1 Genomic coordinates (GRCh38): 2:222,423,987-222,562,620 (from NCBI)

▼ Description
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SGPP2 catalyzes the degradation of S1P (Ogawa et al., 2003).

▼ Cloning and Expression
By EST database analysis using SGPP1 (612826) as query, Ogawa et al. (2003) identified SGPP2. The deduced 399-amino acid protein has a calculated molecular mass of 44.7 kD and shares 39.3% amino acid identity with SGPP1. SGPP2 has an N-terminal hydrophobic region, 3 conserved phosphatase-family motifs, and is predicted to be an integral membrane protein with as many as 9 membrane-spanning segments. Immunofluorescence microscopy showed a reticular staining pattern in the perinuclear and cytosolic regions of HEK293 cells, and SGPP2 colocalized with an endoplasmic reticulum antibody. Northern blot analysis of human tissues detected a 5.1-kb transcript with high expression in kidney and heart, followed by brain, colon, lung, and small intestine. A 1.7-kb transcript showed a similar but weaker expression pattern.

▼ Gene Function
Ogawa et al. (2003) demonstrated that SGPP2 exhibited high phosphohydrolase activity against S1P and dihydro-S1P in HEK293 cells.

Mechtcheriakova et al. (2007) demonstrated that SGPP2 is upregulated by inflammatory stimuli, such as TNFA (191160) and lipopolysaccharide in neutrophils, endothelial cells, and other cell types. Electrophoretic mobility shift assay showed that NF-kappa-B (164011) regulated SGPP2 transcription. RNAi reduction of SGPP2 expression in endothelial cells led to decreased TNFA-induced interleukin 1-beta (IL1B; 147720) mRNA and protein, and partial reduction of induced interleukin-8 (IL8; 146930). Mechtcheriakova et al. (2007) detected increased SGPP2 mRNA expression in the skin lesions of patients with psoriasis (see PSORS1; 177900) and suggested that SGPP2 may play a role in proinflammatory signaling.