Focus on Molecules: Tear lipocalin

Abstract

1. Structure Tear lipocalin, or von Ebner’s gland protein, tear specific prealbumin, (GenBank Accession Number: BC074925; Ref Seq ID: NM_002297; PDB ID: 3EYC, 1XKI) is a 17.45 kDa member of a superfamily christened lipocalins because lipophiles are enclosed within their cup shaped cavity or calyx. Tear lipocalin is the predominant lipid carrier in human tears and is critical to functions involving lipids in protection of the ocular surface. The protein exploits a number of structural elements to bind an extremely broad range of ligands that includes a variety of lipids with long alkyl chains, charged moieties, and even polycyclic structures. At ~75 μM, tear lipocalin is second only to lysozyme as the most concentrated protein in human tears. Lipocalin-1 (LCN-1), the name of the gene that encodes tear lipocalin, resides in a lipocalin gene cluster on chromosome 9q34. Two other genes LCN1b and LCN1c are not translated. Three isoforms have been consistently identified in protein sequence data and mass spectrometry in human tears. Genetic polymorphism is unlikely to be the source of these isoforms; at least three laboratories have found only one identical cDNA sequence in several tissues. Mass spectrometry and protein sequencing data combined with the inter-study variability of other isoforms suggest proteolytic action on the major isoform may account for the other forms. In one study tear lipocalin was proffered as the predominant phosphoprotein in tears although phosphorylation of the major isoforms was not evident by mass spectrometry in another study.