Focus on molecules: lacritin.

Lacritin is a 12.3 kDa secreted tear protein in human (accession Q9GZZ8 [Genpept; UniProt; Sanghi et al., 2001]) and non-human primates. It consists of 119 aa after removal of the signal peptide (SP; Fig. 1) and has a predicted isoelectric point (pI ) of 5. Predicted values for secreted lacritin in non-human primates include the following: 12.2 kDa and pI of 5 (Chlorocebus aethiops), 12.3 kDa and pI of 4.8 (Macaca fascicularis), 12.2 kDa and pI of 4.8 (Macaca mulatta), and 12.2 kDa and pI of 5 (Pan troglodytes). By SDS PAGE, lacritin mobility is greater than expected (bacterial recombinant without SP migrates at approximately 18 kDa [Wang et al., 2006]). Several conserved a-helices are predicted (Fig. 1). Two have been confirmed by circular dichroism using the synthetic peptides LKSIVEKSILLTEQALAKAGKGMH and KQFIENGSEFAQKLLKKFS (respectively, amino acids 65e88 and 95e113 of human lacritin without SP; predicted a-helix underlined; Wang et al., 2006). ‘Helical Wheel’ predicts that the latter is strongly amphipathic with hydrophobic and hydrophilic residues on separate faces. Amphipathic a-helices support ligandereceptor and ligandeligand binding (i.e., respectively, PTHLHePTHR1 and VEGFeVEGF). Deletion analysis suggests that the predicted amphipathic a-helix is a binding domain for the N-terminus of deglycanated syndecan-1 (SDC1; Ma et al., 2006). SDC1 is a proteoglycan co-receptor for several different growth factors. NetOGlyc 3.1 suggests 11 sites of O-glycosylation, almost all in the N-terminal half (Fig. 1). One N-glycosylation site is predicted at the C-terminus. Lacritin splice variants have been recently detected at very low levels in two normal lacrimal glands (NCBI Aceview). Lacritin-b (11.1 kDa; 108 aa; pI 5.3 [without SP]) lacks the sequence SIVEKSILTE from exon 4. Lacritinc (10.7 kDa; 119 aa; pI 4.6 [without SP]) lacks exon 4 and 5. A novel 39 aa sequence from intron 3 forms its C-terminus. Lacritin-b and -c are conserved in P. troglodytes. Lacritin was proposed by one group to be a homologue of dermcidin (referenced in Wang et al., 2006). This has not been supported by NCBI Homologene. Sequence identity