Focus on molecules: lacritin.
Focus on molecules: lacritin.
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关注分子：乳泌素。
DOI：
10.1016/j.exer.2007.01.025
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发表时间：
2008
影响因子：
3.4
通讯作者：
Laurie,GordonW
中科院分区：
文献类型：
--
作者：
Ma,Peisong;Wang,Ningning;McKown,RobertL;Raab,RonaldW;Laurie,GordonW
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: 12.2 kDa and pI of 5 (C. aethiops), 12.3 kDa and pI of 4.8 (M. fascicularis), 12.2 kDa and pI of 4.8 (M. mulatta), and 12.2 kDa and pI of 5 (P. troglodytes). By SDS PAGE, lacritin mobility is greater than expected (bacterial recombinant w/o SP migrates at approximately 18 kDa [Wang et al., 2006]). Several conserved α-helices are predicted (Fig. 1). Two have been confirmed by circular dichroism using the synthetic peptides LKSIVEKSILLTEQALAKAGKGMH and KQFIENGSEFAQKLLKKFS (respectively amino acids 65–88 and 95–113 of human lacritin without SP; predicted α-helix underlined; Wang et al., 2006).‘HelicalWheel’predicts that the latter is strongly amphipathic with hydrophobic and hydrophilic residues on separate faces. Amphipathic α-helices support ligand-receptor and ligand-ligand binding (ie. respectively PTHLH-PTHR1 and VEGFVEGF). Deletion analysis suggests that the predicted amphipathic α-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-glycoslyation 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. Lacritin-c (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,’06). This has not been supported by NCBI Homologene. Sequence identity is 29% without the SP but regions of PONDR–predicted disorder approximately align. Both proteins are of similar size and function, and genes for each are immediately adjacent on human chromosome 12q13. An IPR003982 (LTB4R2) domain was assigned to lacritin between aa 10 and 114 (with SP) based on homology of lacritin aa 9* Corresponding author, Email address: glaurie@ virginia. edu (GW Laurie).
