Alternative titles; symbols
HGNC Approved Gene Symbol: LCN1
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38) : 9:135,521,440-135,526,540 (from NCBI)
Lipocalins are a group of extracellular proteins, first described by Pervaiz and Brew (1987), that are able to bind lipophiles by enclosure within their structures, minimizing solvent contact. Based on the known 3-dimensional structure of 5 members of the lipocalin family, i.e., retinol binding protein (180250), beta-lactoglobulin (see 173310), bilin binding protein, mouse major urinary protein, and rat urinary alpha-2-globulin, the general architecture appears to be highly appropriate for binding a variety of hydrophobic ligands. On the basis of highly conserved amino acid sequences and of a size around 18 to 20 kD, about 20 proteins have been designated as lipocalins.
In tear fluid, a group of 6 proteins with molecular weights ranging from 15 to 20 kD and various isoelectric points are abundant. The N-terminal sequences of these proteins led Lassagne and Gachon (1993) to hypothesize that they are isoforms and belong to the lipocalin family. Redl et al. (1992) isolated and partially sequenced tear prealbumin. Based on that sequence, the authors were able to clone a cDNA from a lacrimal gland library predicted to encode a 176-amino acid protein that shares 58% identity to the von Ebner gland protein of the rat and significant homology with other lipocalins including beta lactoglobulin. Northern blots probed with a radiolabeled N-terminal oligonucleotide showed a 0.8-kb mRNA in human lacrimal gland mRNA. Redl et al. (1992) predicted the tear prealbumin protein to be structurally similar to beta lactoglobulin and showed it to bind radiolabeled retinol in vitro. From genetic and biochemical data, they concluded that tear prealbumin is a member of the lipophilic-ligand carrier protein superfamily. Though tear prealbumin was originally described as a tear-specific protein, Redl et al. (1992) showed that tear prealbumin-specific antiserum reacted with human saliva, sweat, and nasal mucus proteins.
Von Ebner glands (VEG) are small lingual salivary glands. Their ducts open into trenches of circumvallate and foliate papillae, and their secretions influence the milieu where the interaction between taste receptor cells and sapid molecules takes place. ('Sapid' means 'possessing taste.') The major secretion of human VEG is a protein with a molecular mass of 18 kD. This VEG protein is identical to lipocalin-1. Blaker et al. (1993) isolated a cDNA clone from a human VEG library and showed that it contained an insert of 735 bp, including an open reading frame that encodes the human VEG protein of 176 amino acids. The VEG proteins are members of the lipocalin protein superfamily; together with odorant-binding protein (164320), they constitute a new subfamily. Sequence similarity to proteins such as retinol binding protein (e.g., 180260) and odorant binding protein suggests a possible function for the human VEG protein in taste perception.
Using Northern blotting and immunohistology, Holzfeind et al. (1996) found that LCN1 is expressed in the human prostate. Cloning and sequencing showed that the transcript is identical to that found in tears. This finding suggested to Holzfeind et al. (1996) that the lipocalin-1 protein is not specific to tears and saliva, as was previously believed, but is multifunctional.
Using a clone from a cDNA library constructed from human lacrimal glands, Lassagne et al. (1993) mapped the gene for tear lipocalin (LCN1) to 9q34 by isotopic in situ hybridization. Five other members of the lipocalin family mapped to the same region: orosomucoid (138600), alpha-1-microglobulin (176870), progestagen-associated endometrial protein (173310), the gamma chain of C8 (120930), and prostaglandin D2 synthase (176803). Chan et al. (1994) demonstrated by in situ hybridization that the LCN1 gene, like several other genes in the lipocalin superfamily, is located in 9q34. Chan et al. (1994) placed the LCN1 gene close to the lipocalin-2 gene (600181). Since the locus homologous to LCN2 is on mouse chromosome 2, the homolog of LCN1 may also be located there. Contradictory results were obtained by Baumgartner et al. (1994) who, using a genomic tear prealbumin probe, mapped LCN1 to 8q24 by fluorescence in situ hybridization. The contradictory results concerning localization of the LCN1 gene were resolved by Herzog et al. (1995), who used hamster/human hybrid cells for PCR experiments and demonstrated localization on chromosome 9. Furthermore, Lassagne et al. (1995), using a panel of hybrid cell lines that had been generated and characterized by Nguyen Van Cong et al. (1986) and Glasgow et al. (1993), likewise assigned it to 9q34-qter by somatic cell hybrid analysis.
Lacazette et al. (1997) reported a dinucleotide repeat microsatellite marker (D9S1826) close to the LCN1 gene. Using the CEPH reference families, they located the LCN1 gene within the 9q34 genetic map between D9S23 and D9S158.
Van't Hof et al. (1997) showed that LCN1 inhibits the cysteine-protease papain in vitro, similar to cystatins (see 123857). They suggested that LCN1 plays a role in the nonimmunologic defense and in the control of inflammatory processes in oral and ocular tissues.
Redl et al. (1998) found enhanced LCN1 secretion in the airways of patients with cystic fibrosis (CF; 219700). Northern blot analysis of RNA from normal trachea and RNA isolated from tracheal biopsies of patients with CF indicated that the enhanced secretion was due to an upregulated expression of the LCN1 gene. Thus, the investigations presented the first clear evidence that LCN1 is induced in infection or inflammation and supported the idea that this lipocalin functions as a physiologic protection factor of epithelia in vivo.
Baumgartner, M., Holzfeind, P., Redl, B. Assignment of the gene for human tear prealbumin (LCN1), a member of the lipocalin superfamily, to chromosome 8q24. Cytogenet. Cell Genet. 65: 101-103, 1994. [PubMed: 8404058] [Full Text: https://doi.org/10.1159/000133610]
Blaker, M., Kock, K., Ahlers, C., Buck, F., Schmale, H. Molecular cloning of human von Ebner's gland protein, a member of the lipocalin superfamily highly expressed in lingual salivary glands. Biochim. Biophys. Acta 1172: 131-137, 1993. [PubMed: 7679926] [Full Text: https://doi.org/10.1016/0167-4781(93)90279-m]
Chan, P., Simon-Chazottes, D., Mattei, M. G., Guenet, J. L., Salier, J. P. Comparative mapping of lipocalin genes in human and mouse: the four genes for complement C8 gamma chain, prostaglandin-D-synthase, oncogene-24P3, and progestagen-associated endometrial protein map to HSA9 and MMU2. Genomics 23: 145-150, 1994. [PubMed: 7829063] [Full Text: https://doi.org/10.1006/geno.1994.1470]
Glasgow, B. J., Heinzmann, C., Kojis, T., Sparkes, R. S., Mohandas, T., Bateman, J. B. Assignment of tear lipocalin gene to human chromosome 9q34-9qter. Curr. Eye Res. 12: 1019-1023, 1993. [PubMed: 8306712] [Full Text: https://doi.org/10.3109/02713689309029229]
Herzog, H., Baumgartner, M., Holzfeind, P., Redl, B. Confirmation of 9q34 as the chromosomal site of the human lipocalin LCN1 gene. Cytogenet. Cell Genet. 69: 108-109, 1995. [PubMed: 7835076] [Full Text: https://doi.org/10.1159/000133949]
Holzfeind, P., Merschak, P., Rogatsch, H., Culig, Z., Feichtinger, H., Klocker, H., Redl, B. Expression of the gene for tear lipocalin/von Ebner's gland protein in human prostate. FEBS Lett. 395: 95-98, 1996. [PubMed: 8898072] [Full Text: https://doi.org/10.1016/0014-5793(96)01008-3]
Lacazette, E., Pitiot, G., Jobert, S., Mallet, J., Gachon, A. M. F. Fine genetic mapping of LCN1/D9S1826 within 9q34. Ann. Hum. Genet. 61: 449-455, 1997. [PubMed: 9459006] [Full Text: https://doi.org/10.1046/j.1469-1809.1997.6150449.x]
Lassagne, H., Gachon, A. M. F. Cloning of a human lacrimal lipocalin secreted in tears. Exp. Eye Res. 56: 605-609, 1993. [PubMed: 8500570] [Full Text: https://doi.org/10.1006/exer.1993.1075]
Lassagne, H., Nguyen, V. C., Mattei, M. G., Gachon, A. M. F. Assignment of LCN1 to human chromosome 9 is confirmed. Cytogenet. Cell Genet. 71: 104 only, 1995. [PubMed: 7606920] [Full Text: https://doi.org/10.1159/000134073]
Lassagne, H., Ressot, C., Mattei, M. G., Gachon, A. M. F. Assignment of the human tear lipocalin gene (LCN1) to 9q34 by in situ hybridization. Genomics 18: 160-161, 1993. [PubMed: 8276406] [Full Text: https://doi.org/10.1006/geno.1993.1444]
Nguyen Van Cong, Weil, D., Finaz, C., Cohen-Haguenauer, O., Gross, M.-S., Jegou-Foubert, C., de Tand, M.-F., Cochet, C., de Grouchy, J., Frezal, J. Panel of twenty-five independent man-rodent hybrids for human genetic marker mapping. Ann. Genet. 29: 20-26, 1986. [PubMed: 3487271]
Pervaiz, S., Brew, K. Homology and structure-function correlations between alpha-1-acid glycoprotein and serum retinol-binding protein and its relatives. FASEB J. 1: 209-214, 1987. [PubMed: 3622999] [Full Text: https://doi.org/10.1096/fasebj.1.3.3622999]
Redl, B., Holzfeind, P., Lottspeich, F. cDNA cloning and sequencing reveals human tear prealbumin to be a member of the lipophilic-ligand carrier protein superfamily. J. Biol. Chem. 267: 20282-20287, 1992. [PubMed: 1400345]
Redl, B., Wojnar, P., Ellemunter, H., Feichtinger, H. Identification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis. Lab. Invest. 78: 1121-1129, 1998. [PubMed: 9759656]
van't Hof, W., Blankenvoorde, M. F. J., Veerman, E. C. I., Nieuw Amerongen, A. V. The salivary lipocalin Von Ebner's Gland protein is a cysteine proteinase inhibitor. J. Biol. Chem. 272: 1837-1841, 1997. [PubMed: 8999869] [Full Text: https://doi.org/10.1074/jbc.272.3.1837]