Disease relevance of SLURP1

• Mutations in the SLURP1 gene are the cause of Mal de Meleda (MDM), a rare autosomal recessive genetic disease, characterized by inflammatory palmoplantar keratoderma [1].
• Conditions that typically occur late in the course of AIDS such as Mycobacterium avium infection and cytomegalovirus disease, were more frequently recorded by ASD than by ARS [2].
• PATIENTS AND METHODS: Sera from patients with polymyositis and sera found to contain anticytoplasmic antibodies were screened for antibody to PL-12 by testing for inhibition of ARS enzymatic activity by serum, and by immunoprecipitation [3].
• BACKGROUND: Tibial muscular dystrophy (TMD), a late-onset dominant distal myopathy, is caused by yet unknown mutations on chromosome 2q, whereas MD with myositis (MDM) is a muscular dystrophy of the mouse, also progressing with age and linked to mouse chromosome 2 [4].
• Comparison of the histologic and clinical prognostic indicators of mortality in patients who have malignant melanoma with the clinical and pathologic features seen in this series of 21 patients would appear to indicate a diminished tendency toward metastatic or recurrent disease in patients with MDM and BM [5].

Psychiatry related information on SLURP1

• The SCS/ARS/CES pesticide properties database for environmental decision-making [6].

High impact information on SLURP1

• The arsenic resistance efflux system transports arsenite, using alternatively either a two-component (ArsA and ArsB) ATPase or a single polypeptide (ArsB) functioning as a chemiosmotic transporter [7].
• In vitro experiments revealed that ArsB and ArsC, sharing 71% amino acid sequence identity, were an alkylresorcinol synthase and an alkylpyrone synthase, respectively, indicating that ArsB and ArsC are not isozymes but enzymatically distinct polyketide synthases [8].
• The ars operon consisted of four genes, two of which encoded a type III polyketide synthase, ArsB and ArsC [8].
• It has been shown recently that amino acid substitution at the antigen recognition site (ARS) is more rapid than synonymous substitution, suggesting some kind of positive natural selection working at the ARS [9].
• These results identify SLURP-1 as a secreted epidermal neuromodulator which is likely to be essential for both epidermal homeostasis and inhibition of TNF-alpha release by macrophages during wound healing [10].

Chemical compound and disease context of SLURP1

• METHODS: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests [11].
• Sixteen Pseudomonas aeruginosa strains, including patent strain NRRL B-18602, three recent isolates from composted materials amended with ricinoleic acid, and 12 randomly selected from the holdings of the ARS Culture Collection, were examined for their fatty acid converting abilities [12].

Biological context of SLURP1

• Transfected human embryonic kidney 293T cells expressed the MDM mutant SLURP1 containing the single amino-acid substitution G86R but did not tolerate the MDM mutation W15R located in the signal peptide [1].
• We report the refinement of our previously described interval of MDM on chromosome 8qter, and the identification of mutations in affected individuals in the ARS (component B) gene, encoding a protein named SLURP-1, for secreted Ly-6/uPAR related protein 1 [13].
• Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda [10].
• SLURP-1 belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins, which participate in signal transduction, immune cell activation or cellular adhesion [10].
• Thus, the changes in the cell state induced by SLURP-1 could result from nAChR-mediated effects on the KC gene expression [14].

Anatomical context of SLURP1

• In the epidermis, keratinocytes underlying the stratum corneum are highly positive for SLURP1 immunostaining and cultured keratinocytes secrete the expected 9 kD protein [15].
• Novel mutations in the gene encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) and description of five ancestral haplotypes in patients with Mal de Meleda [16].
• The N-terminal amino acid sequence of the anti-neoplastic urinary protein (ANUP), a unique cytokine present in human granulocytes, was determined to be: Pyroglu-Leu-Lys-X-Tyr-Thr-X-Lys-Glu-Pro-Met-Thr-Ser(Thr)-Ala-Ala... This sequence showed no significant homology with any other protein when used in database searches [17].
• A urinary protein with antitumor activity, ANUP (antineoplastic urinary protein), a dimer of 32 kD, has previously been shown to inhibit the growth of various tumor cell lines in vivo [18].
• ANUP also inhibited the proliferation of endothelial cell lines, suggesting that the in vitro effects were endothelial cell lineage-specific [18].

Associations of SLURP1 with chemical compounds

• We found that SLURP-1 potentiates the human alpha 7 nicotinic acetylcholine receptors that are present in keratinocytes [10].
• In the presence of the agonist carbachol, the effects of SLURP-1 on gene expression were augmented, which is in keeping with the notion that SLURP-1 acts as an allosteric agonist at the KC nAChR [14].
• Since the SLURP-1 gene maps to the same chromosomal region as several members of the Ly-6/uPAR subfamily of glycoprotein receptors, it is suggested that both biologically distinct subfamilies might have co-evolved from local chromosomal duplication events [19].
• ArsA is the catalytic subunit of the arsenical pump, coupling ATP hydrolysis to the efflux of arsenicals through the ArsB membrane protein [20].
• METHODS: After initial treatment of reflux oesophagitis with omeprazole to control symptoms and to heal oesophagitis, 154 patients were randomised to continue treatment with omeprazole (20 or 40 mg daily) and 144 patients to have an open antireflux operation (ARS) [21].

Other interactions of SLURP1

• A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish families with mal de Meleda: evidence of a founder effect [22].
• The high degree of structural similarity between SLURP-1 and the three fingers motif of snake neurotoxins and Lynx1 suggests that this protein interacts with the neuronal acetylcholine receptors [10].

Analytical, diagnostic and therapeutic context of SLURP1

• Thus, most MDM mutations in SLURP1 affect either the expression, integrity, or stability of the protein, suggesting that a simple immunologic test could be used as a rapid screening procedure [1].
• In case of GORD relapse, patients allocated to omeprazole were offered ARS and those initially operated on had either a reoperation or were treated with omeprazole [21].
• METHODS: Skin tests were performed with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin (AX), and ampicillin at the initial evaluation and repeated 1, 3, and 5 years later if the responses were still positive [23].
• A retrospective study of 21 patients with the histopathologic diagnosis of minimal deviation melanoma (MDM; n = 18) and borderline melanoma (BM; n = 3) was undertaken to determine the prognosis for these patients compared with that for patients with other types of malignant melanoma [5].
• Skin tests were carried out with major and minor determinants of benzylpenicillin (BPO and MDM), amoxicillin (AX), and ampicillin (AMP), and specific IgE antibodies were determined by radioallergosorbent test (RAST) [24].

References