Disease relevance of SACM1L

• Cord blood B lymphocytes present in isolated cord blood mononuclear cell (MNC) preparations are normally unable to differentiate into immunoglobulin secreting plaque forming cells (PFC) when cultured in the presence of pokeweed mitogen (PWM) alone or killed Staphylococcus aureus Cowan 1 (SAC1) alone [1].

High impact information on SACM1L

• Therefore, we have cloned human SAC1 (hSAC1), show that it behaves similar to ySac1p in terms of substrate specificity, demonstrate that the endogenous protein localizes to the ER and Golgi, and identify for the first time members of the coatomer I (COPI) complex as interaction partners of hSAC1 [2].
• Site-directed mutagenesis further illustrated its functional similarity to the catalytic domain of Sac1 proteins [3].
• Sac1p shares primary sequence homology with a subfamily of cytosolic/peripheral membrane phosphoinositide phosphatases, the synaptojanins, and these Sac1 domains define novel phosphoinositide phosphatase modules [4].
• Biochemical and in vivo data indicate that rat Sac1 phosphatidylinositol-4-phosphate phosphatase activity, but not its phosphatidylinositol-3-phosphate or phosphatidylinositol-3, 5-bisphosphate phosphatase activities, is essential for the heterologous complementation of Sac1p defects in vivo [4].
• Like Sac1p, rat Sac1 exhibits intrinsic phosphoinositide phosphatase activity directed toward phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol 3,5-bisphosphate substrates, and we identify mutant rat sac1 alleles that evoke substrate-specific defects in this enzymatic activity [4].

Biological context of SACM1L

• Finally, rat Sac1 expression in Deltasac1 yeast strains complements a wide phenotypes associated with Sac1p insufficiency [4].

Anatomical context of SACM1L

• Thus, yeast Sac1p and rat Sac1 are integral membrane lipid phosphatases that play evolutionary conserved roles in eukaryotic cell physiology [4].
• Rat Sac1 is a ubiquitously expressed 65-kDa integral membrane protein of the endoplasmic reticulum that is found at particularly high levels in cerebellar Purkinje cells [4].
• To examine these control mechanisms, the B cell responses to 4 mitogens (pokeweed, wheat germ agglutinin, lipopolysaccharide, and SAC-1), which are known to stimulate B cells by different mechanisms, were measured in two groups of stable long-term (greater than 1 year post-transplant) renal transplant recipients [5].
• The action of PWM and SAC1 on cord blood MNC can each be replaced by conditioned media [1].

Associations of SACM1L with chemical compounds

• Functional characterization of a mammalian Sac1 and mutants exhibiting substrate-specific defects in phosphoinositide phosphatase activity [4].
• The influence of amino acids and their derivatives on the formation of SAC14 from SAC1 and C4 were investigated [6].

Analytical, diagnostic and therapeutic context of SACM1L

• DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu [7].
• The bZP2 cDNA (115-1914 nt, 1.8 kb), excluding sequences coding for N-terminal signal sequence and C-terminal transmembranelike domain, was PCR amplified and Sac1-Sal1 restricted fragment cloned in frame downstream of the T5 promoter under the lac operator control in a pQE-30 vector [8].

References