Alternative titles; symbols
HGNC Approved Gene Symbol: CHID1
Cytogenetic location: 11p15.5 Genomic coordinates (GRCh38): 11:867,859-915,214 (from NCBI)
Mammalian GLYCO18 domain-containing proteins include catalytically active chitinases (e.g., CHIT1; 600031) and chitinase-like proteins (e.g., CHI3L1; 601525) with cytokine activity involved in host defense and Th2 inflammatory reactions. CHID1 is a GLYCO18 domain-containing protein that lacks catalytic amino acids and a chitin-binding domain. CHID1 interacts with the endocytic/sorting receptor stabilin-1 (STAB1; 608560) and is present in late endosomes and secretory lysosomes in alternatively activated macrophages (Kzhyshkowska et al., 2006).
Using a yeast 2-hybrid screen of a placenta cDNA library with STAB1 as bait, followed by database analysis, Kzhyshkowska et al. (2006) identified human CHID1, which they called SICLP. The deduced 393-amino acid protein has a calculated molecular mass of 44.9 kD. It contains an N-terminal signal sequence and a GLYCO18-like domain, but it lacks a chitin-binding domain and catalytic amino acids. Western blot analysis showed high expression of 33- and 39-kD proteins in human monocyte, embryonic kidney, and B-cell lines, as well as in human bronchoalveolar lavage and peripheral blood cells, but only low levels were detected in T-cell and epithelial cell lines. Immunofluorescence and confocal microscopy demonstrated localization of SICLP in LAMP1 (153330)-positive/CD63 (155740)-positive lysosomes and p62 (SQSTM1; 601530)-positive late endosomes.
Using protein pull-down assays, Kzhyshkowska et al. (2006) confirmed interaction between STAB1 and SICLP and showed that the interaction occurred through fasciclin domain-7 of STAB1. RT-PCR analysis showed upregulated expression of CHID1 in human macrophages after stimulation with IL4 (147780) and/or dexamethasone and revealed that IFNG (147570) suppressed this effect. Knockdown of STAB1 resulted in decreased sorting of CHID1 from late Golgi compartments to lysosomes. Kzhyshkowska et al. (2006) concluded that CHID1 is a chitinase-like secreted protein that interacts with STAB1.
Using the hanging-drop vapor diffusion method, Meng et al. (2009) generated crystal images of SICLP at 2.7-angstrom resolution. Further analysis of the structure by Meng et al. (2010) showed a typical triose-phosphate isomerase barrel fold with an atypically wide and open saccharide-binding cleft. Binding studies indicated a preference for chitotetraose and a capacity to bind lipopolysaccharide (LPS) and neutralize its endotoxin effect on macrophages. Meng et al. (2010) proposed that SICLP may play a role in pathogen sensing.
Gross (2014) mapped the CHID1 gene to chromosome 11p15.5 based on an alignment of the CHID1 sequence (GenBank BC000001) with the genomic sequence (GRCh37).
Gross, M. B. Personal Communication. Baltimore, Md. 3/13/2014.
Kzhyshkowska, J., Mamidi, S., Gratchev, A., Kremmer, E., Schmuttermaier, C., Krusell, L., Haus, G., Utikal, J., Schledzewski, K., Scholtze, J., Goerdt, S. Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway. Blood 107: 3221-3228, 2006. [PubMed: 16357325] [Full Text: https://doi.org/10.1182/blood-2005-07-2843]
Meng, G., Bai, X., Green, T. J., Luo, M., Zheng, X. Crystallization and preliminary X-ray crystallographic studies on SI-CLP, a novel human Glyco_18 domain-containing protein. Protein Peptide Lett. 16: 336-338, 2009.
Meng, G., Zhao, Y., Bai, X., Liu, Y., Green, T. J., Luo, M., Zheng, X. Structure of human stabilin-1 interacting chitinase-like protein (SI-CLP) reveals a saccharide-binding cleft with lower sugar-binding selectivity. J. Biol. Chem. 285: 39898-39904, 2010. [PubMed: 20724479] [Full Text: https://doi.org/10.1074/jbc.M110.130781]