Disease relevance of LRRCC1

• In contrast, in a mouse model of oesophageal candidiasis in which dissemination into internal organs did not occur, no SAP2 expression was detected at any time [1].
• Reverse transcription - 3' rapid amplification of cDNA ends-nested PCR of ACT1 and SAP2 mRNA as a means of detecting viable Candida albicans in an in vitro cutaneous candidiasis model [2].
• Mutational analysis in a patient with a variant form of Gaucher disease caused by SAP-2 deficiency [3].

High impact information on LRRCC1

• When human skin fibroblast extracts were subjected to sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by electroblotting and immunochemical staining using monospecific antibodies against SAP-2, two or three major bands with estimated mol. wts. of 9,000-10,000 were found [4].
• Assignment of the gene for human sphingolipid activator protein-2 (SAP-2) to chromosome 10 [4].
• Sphingolipid activator protein-2 (SAP-2) has been found to stimulate the enzymatic hydrolysis of glucosylceramide, galactosylceramide, and sphingomyelin [4].
• Therefore, the signals and signal transduction pathways that mediate SAP2 expression within certain host niches may differ from those that activate the gene in vitro [5].
• A cassette was constructed that, in addition to the URA3 selection marker, contained an inducible SAP2P-FLP fusion and was flanked by direct repeats of the minimal FLP recognition site (FRT) [6].

Biological context of LRRCC1

• The FLP gene, encoding the site-specific recombinase FLP, was genetically modified for expression in C. albicans and fused to the promoter of the SAP2 gene that codes for one of the secreted aspartic proteinases, which are putative virulence factors of C. albicans [1].
• CPxxCxCxxxxVxCxxxxLxxxPxxxPx(10~58) Nx(19,20)LxxNx(9)Fx(8)LxLxxNxxxCxxxxxFxxLxxx xxLxLxxNx(9)Fx(13)NxxxCxCxxxWLx(15)CxxPx(17)C was the consensus sequence of LRRCC domain [7].

Anatomical context of LRRCC1

• Experiments with cultured cells suggest that in vivo this glycoprotein requires interaction with negatively charged lipids and a small acidic protein, SAP-2, for optimal glucosylceramide hydrolytic rates [8].

Associations of LRRCC1 with chemical compounds

• SAP-2 has previously been demonstrated to activate the hydrolysis of glucosylceramide, galactosylceramide, and, possibly, sphingomyelin [9].
• The SAP2P-FLP fusion was integrated into one of the SAP2 alleles in a strain that contained a deletable marker that conferred resistance to mycophenolic acid and was flanked by direct repeats of the FLP recognition target (FRT) [1].
• Transcript profiling indicated antifungal exposure was associated with increased expression of mRNA from SAP2 and SAP9 genes; this was confirmed for fluconazole and caspofungin exposure by RT-PCR [10].
• Form I glucocerebrosidase was stimulated by sodium taurocholate or sphingolipid-activator protein 2 (SAP-2), whereas form II enzyme exhibited maximal activity in the absence of the effectors [11].
• Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa [12].

Analytical, diagnostic and therapeutic context of LRRCC1

• We developed an avidin-biotin-amplified immunofluorometric assay for the detection of specific immunoglobulins G, A, and M against somatic, Sap2 and Sap6 antigens [13].
• Consistent with immunoblotting studies on electrophoretograms, both the patient and his affected fetal sibling were found to be deficient in immunoreactive SAP-2 [14].
• Epitope mapping Candida albicans proteinase (SAP 2) [15].
• Activation of the enzyme by taurocholate, phosphatidylserine and sphingolipid activator protein 2 (saposin C; SAP-2) was investigated by titration of combinations of various effectors in the absence and presence of Triton X-100 [16].

References