Cloning, modeling, and chromosomal localization for a smallleucine-rich repeat proteoglycan (SLRP) family member expressed in humaneye

[摘要] Purpose: To examine a highly abundant novel transcript from humaniris.Methods: Expressed sequence tag (EST) analysis of an adult humaniris cDNA library revealed an abundant (>0.7%) transcript for a novelmember of the small leucine-rich proteoglycan (SLRP) family. Other 3'ESTs from retina were also detected in dbEST. The structure of theleucine-rich repeat (LRR) domain was investigated by molecular modeling.Antisera were raised against a specific peptide and used in westernblots of human and rat eye tissues.Results: From its prevalence in the eye and its superfamilyrelationships, this SLRP protein has been given the names oculoglycan oropticin (Optc). Sequence analysis suggests that Optc has a signalpeptide and two structural domains, the larger of which is the LRRdomain. Modeling of the LRR domain reveals structural variability in therepeat motifs, forming potential interaction sites for binding partners.Antiserum to a specific peptide detected a protein of approximately 48kDa, in human iris, ciliary body and retina while the major proteindetected in rat ocular tissues was 37 kDa in size. This may reflect aspecies difference in post-translational modification. Radiation hybridmapping shows that the gene for OPTC is located on chromosome 1q31,close to the inherited eye diseases ARMD1 and AXPC1.Conclusions: Optc is a newly identified SLRP family member, whichappears to have eye-preferred expression. Molecular modeling revealslocal deviations from the familiar LRR structure, which are candidatesfor specific interaction sites. Western blotting with a specific peptideantibody detects Optc in iris, ciliary body and retina in the human eyeand suggests that the protein is post-translationally modified. In rat,the antibody detects Optc in several eye tissues and in brain but theprotein appears to have undergone much less modification, suggestingthat this is not essential for all aspects of function. Considering itseye-preferred expression, the OPTC gene has the potential forinvolvement in inherited eye disease. Indeed, it maps close to at leasttwo disease loci for which no gene has so far been identified.

[学科分类] 生物化学/生物物理