Alternative titles; symbols
HGNC Approved Gene Symbol: COLEC12
Cytogenetic location: 18p11.32 Genomic coordinates (GRCh38) : 18:316,737-500,701 (from NCBI)
Collectins are a family of C-type lectins that have collagen-like sequences and carbohydrate recognition domains. They are involved in host defense through their ability to bind to carbohydrate antigens of microorganisms.
Using rat Limk2 (601988) as bait in a yeast 2-hybrid screen, Nakamura et al. (2001) cloned COLEC12, which they designated SRCL, from a placenta cDNA library. The deduced 742-amino acid protein has a calculated molecular mass of about 82 kD. COLEC12 contains an N-terminal leucine zipper transmembrane region, a coiled-coil domain, a collagen domain, and a C-terminal C-type lectin/carbohydrate recognition domain. It also has several putative sites for N-glycosylation, a serine/threonine-rich region, and a putative internalization signal. Nakamura et al. (2001) also cloned an isoform that did not contain the C-type carbohydrate recognition motif. Northern blot analysis detected expression of a major 3.0-kb transcript at highest levels in placenta, followed by lung, heart, and small intestine. Additional transcripts of 9.0, 6.5, 4.5, and 2.5 kb were detected in placenta. Moderate expression was found in several other tissues, but was below the level of detection in liver and spleen. Immunolocalization of COLEC12 in transfected Chinese hamster ovary (CHO) cells showed staining of the outer cell surface. Punctate staining indicated that COLEC12 clusters on the cell surface.
Using homology with the conserved C-terminal domain of the collectin family, Ohtani et al. (2001) identified an EST containing COLEC12, which they designated CLP1. Using this sequence as probe, and by cap-site hunting, they cloned full-length COLEC12 from a placenta cDNA library. Northern blot analysis detected expression of a 3.2-kb transcript in placenta, heart, and lung, and RT-PCR detected expression in most tissues examined. Immunohistochemical analysis showed that Colec12 localized to vascular endothelial cells in mouse heart. COLEC12 was detected in most vascular endothelial cells in all murine vessels and human heart sections, but it was not detected in macrophages, monocytes, and hepatic Kupffer cells. Immunoblot and flow cytometric analyses indicated that COLEC12 is a membrane glycoprotein of about 140 kD in human umbilical vein or arterial endothelial cells, placenta membrane extracts, and transfected CHO cells. Deglycosylation of in vitro translated COLEC12 resulted in a protein with an apparent molecular mass of 90 kD. By gel filtration chromatography, a truncated form of COLEC12 lacking the transmembrane domain migrated as a trimer of about 300 kD.
Nakamura et al. (2001) cloned mouse Colec12. The deduced 742-amino acid protein shows the same domain structure as human COLEC12 and shares 92% sequence identity. Northern blot analysis revealed ubiquitous expression of mouse Colec12, including expression in liver and spleen. Nakamura et al. (2001) found high Colec12 expression in a mouse macrophage cell line. During development, Colec12 was expressed in mouse embryos prior to embryonic day 9 (E9). Expression peaked at E14 and gradually decreased until E18.
Nakamura et al. (2001) found that CHO cells transfected with COLEC12 bound to E. coli and S. aureus, but there was no evidence of phagocytosis. Nakamura et al. (2001) showed that mouse Colec12 also mediated binding between E. coli and transfected CHO cells.
Ohtani et al. (2001) found that COLEC12 transfected into CHO cells mediated binding and phagocytosis of bacteria (E. coli and S. aureus) and yeast (S. cerevisiae). It also reacted with oxidized low density lipoprotein (LDL), but not with acetylated LDL. Binding was inhibited by polyanionic ligands and oxidized LDL, but not by polycationic ligands, LDL, or acetylated LDL. Ohtani et al. (2001) concluded that COLEC12 may play a role in host defenses that are different from those of soluble collectins in innate immunity.
Ohmori et al. (2003) sequenced the COLEC12 gene in 10 Japanese volunteers and identified 5 SNPs (2 in intron 2, 1 in exon 5, and 2 in exon 6) with a minor allele frequency of at least 29%. They identified another SNP in the 5-prime upstream region of the gene. Using these 6 SNPs they analyzed the haplotype structure of the gene with DNA derived from 54 individuals. The SNPs in exon 6 led to amino acid substitutions and were thus candidates for influencing disease susceptibility.
By genomic sequence analysis, Nakamura et al. (2001) mapped the COLEC12 gene to chromosome 18p11.32.
Nakamura, K., Funakoshi, H., Miyamoto, K., Tokunaga, F., Nakamura, T. Molecular cloning and functional characterization of a human scavenger receptor with C-type lectin (SRCL), a novel member of a scavenger receptor family. Biochem. Biophys. Res. Commun. 280: 1028-1035, 2001. [PubMed: 11162630] [Full Text: https://doi.org/10.1006/bbrc.2000.4210]
Nakamura, K., Funakoshi, H., Tokunaga, F., Nakamura, T. Molecular cloning of a mouse scavenger receptor with C-type lectin (SRCL), a novel member of the scavenger receptor family. Biochim. Biophys. Acta 1522: 53-58, 2001. [PubMed: 11718900] [Full Text: https://doi.org/10.1016/s0167-4781(01)00284-6]
Ohmori, H., Makita, Y., Funamizu, M., Chiba, S., Ohtani, K., Suzuki, Y., Wakamiya, N., Hata, A. Haplotype analysis of the human collectin placenta 1 (hCL-P1) gene. J. Hum. Genet. 48: 82-85, 2003. [PubMed: 12601552] [Full Text: https://doi.org/10.1007/s100380300011]
Ohtani, K., Suzuki, Y., Eda, S., Kawai, T., Kase, T., Keshi, H., Sakai, Y., Fukuoh, A., Sakamoto, T., Itabe, H., Suzutani, T., Ogasawara, M., Yoshida, I., Wakamiya, N. The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells. J. Biol. Chem. 276: 44222-44228, 2001. [PubMed: 11564734] [Full Text: https://doi.org/10.1074/jbc.M103942200]