Identification and Characterization of Calcium Binding Protein, Spermatid Associated 1 (CABS1) in Selected Human Tissues and Fluids

Abstract

Calcium binding protein, spermatid associated 1 (CABS1) is a protein most widely studied in spermatogenesis. However, mRNA for CABS1 has been found in numerous tissues, albeit with little information about the protein. Previously, we identified CABS1 mRNA and protein in human salivary glands and provided evidence that in humans CABS1 contains a heptapeptide near its carboxyl terminus that has anti-inflammatory activities. Moreover, levels of an immunoreactive form of CABS1 were elevated in psychological stress. To more fully characterize human CABS1 we developed additional polyclonal and monoclonal antibodies to different sections of the protein and used these antibodies to characterize CABS1 in an overexpression cell lysate, human salivary glands, saliva, serum and testes using western blot, immunohistochemistry and bioinformatics approaches exploiting the Gene Expression Omnibus (GEO) database. CABS1 appears to have multiple molecular weight forms, consistent with its recognition as a structurally disordered protein, a protein with structural plasticity. Interestingly, in human testes, its cellular distribution differs from that in rodents and pigs, and includes Leydig cells, primary spermatogonia, Sertoli cells and developing spermatocytes and spermatids, Geodata suggests that CABS1 is much more widely distributed than previously recognized, including in the urogenital, gastrointestinal and respiratory tracts, as well as in the nervous system, immune system and other tissues. Much remains to be learned about this intriguing protein.

SEQSIM – A novel bioinformatics tool for comparisons of upstream gene regions – a case study of calcium binding protein spermatid associated 1 (CABS1)

“…Unique sets of genes associated with different biological pathways, functions, or cellular processes may be represented by these distinct clusters. For example, the identification of protein-coding genes with the highest SEQSIM score to the CABS1 UGR and within the CABS1 cluster, such as VWCE, SPOCK1, THSD4, RNF39 and TMX2, suggests shared regulatory mechanisms and potential strategies to interrogate the regulation and function of this poorly known, but apparently widely distributed gene in human tissues (13,31). Extrapolating from other members of its clusters may help us define the functional role of CABS1 and understand its roles in various biologically processes.…”

“…In Figure 4B, the multiple sequence alignment of the CABS1 UGR with adjacent UGRs with high similarity, LINC02562, MUC7 and RNU4ATAC9P UGRs, reveals small sections of identical sequences, which could correspond to transcription factor binding site motifs (5 to 20 nucleotides long), promoters, enhancers, or other regulatory elements. CABS1 is primarily expressed in testicular tissues and is thought to be involved in the late stages of spermatogenesis, and it also has been found in human saliva (13). Interestingly, MUC7 (mucin-7, secreted) is a member of the mucin family of proteins which is specifically known for its role in saliva, contributing to the innate defense in the oral cavity.…”

“…The CABS1 protein is most abundant in the testis, and found in salivary glands (12). Recent analysis of GeoData has detected CABS1 mRNA widely expressed in human tissues (13). To date, CABS1 has been associated with spermatogenesis in several species and with acute psychological stress in humans (14)(15)(16)(17).…”