ABSTRACT
The scavenger receptor cysteine-rich superfamily (SRCR-SF) is a highly conserved group of membrane and/or secreted proteins related to the innate and adaptive immune system. Here, we report the cloning of the gene encoding human S4D-SRCRB, a novel soluble member of the SRCR-SF, which is composed of four group B SRCR domains separated by Pro-, Ser- and Thr-rich polypeptides. The longest cDNA sequence found is 2,806 bp in length and encodes a mature protein of 528 aa, with a predicted molecular mass of M(r) 55,600. The S4D-SRCRB gene is located at Chromosome 7q11.23, telomeric to the Williams-Beuren syndrome deletion. It extends over 20 kb and consists of 11 exons, with each SRCR domain being encoded by a single exon. Northern blot analysis indicated that S4D-SRCRB has a broad tissue distribution and is expressed as two major mRNA species: one of 2.8 kb, with a restricted tissue expression pattern (mainly kidney and placenta), and another of 1.5 kb, with a broader distribution. A similar mRNA expression pattern was observed during the analysis of several tumor cell lines. The highest degree of similarity found between S4D-SRCRB and other group B SRCR-SF members was with human DMBT1 (a mosaic protein composed of fourteen SRCR domains, which is involved in innate defense and epithelia polarization) and chicken 18-B (a turpentine-induced soluble acute-phase protein composed of four SRCR domains). Our data indicate that S4D-SRCRB constitutes a novel SRCR-SF member, which could be involved in basic homeostatic functions such as innate host defense.
Subject(s)
Chromosomes, Human, Pair 7/genetics , Membrane Proteins , Receptors, Immunologic/chemistry , Receptors, Immunologic/genetics , Receptors, Lipoprotein , Alternative Splicing , Amino Acid Sequence , Base Sequence , Cell Line , Chromosome Mapping , Cloning, Molecular , Cytokines/pharmacology , Exons/genetics , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Introns/genetics , Molecular Sequence Data , Organ Specificity , RNA Splice Sites/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Immunologic/classification , Receptors, Scavenger , Scavenger Receptors, Class B , Sequence Alignment , Sequence Homology, Amino Acid , Solubility , Tumor Cells, CulturedABSTRACT
BACKGROUND AND OBJECTIVES: The gene coding for the human CD5 lymphocyte surface receptor maps to the 11q12.2 region, which is in the vicinity of a region commonly affected by multiple somatic mutations in human cancers. The 5'-flanking region of the human CD5 gene includes an evolutionarily conserved (TC)n(CA)n microsatellite (MS) of potential utility as a marker for genome instability. The aim of the present study was to investigate the value of the CD5 MS as a marker for instability in different tumor types, particularly in B-cell leukemia and lymphoma. DESIGN AND METHODS: The CD5 MS and a panel of 10 MS markers were analyzed by using a polymerase chain reaction (PCR)-based method and polyacrylamide sequencing gels. This was done in several hematopoietic and non-hematopoietic cell lines, as well as in 28 cases of B-cell chronic lymphocytic leukemia (B-CLL), 19 mantle cell lymphomas (MCL) and 45 head and neck carcinomas (HNC). RESULTS: The frequency of CD5 MS abnormalities found among HNC was similar to that reported for other well known MS markers at loci near known and suspected cancer genes. However, instability at the CD5 MS was the most frequent MS abnormality among B-CLL and MCL. INTERPRETATION AND CONCLUSIONS: The inclusion of MS markers at chromosome 11q may be especially informative for genome instability analyses of certain B-cell leukemias and lymphomas.
