HGNC Approved Gene Symbol: CHAD
Cytogenetic location: 17q21.33 Genomic coordinates (GRCh38): 17:50,464,496-50,468,880 (from NCBI)
Chondroadherin (CHAD) was initially described by Larsson et al. (1991) as a 36-kD matrix protein isolated from bovine cartilage. It was shown to mediate chondrocyte-matrix interactions. Analysis of cDNA generated from a bovine chondrocyte mRNA demonstrated that chondroadherin belongs to the family of leucine-rich repeat (LRR) proteins. Of the LRR proteins, chondroadherin is most closely related to the proteoglycans decorin (125255), biglycan (301870), fibromodulin (600245), and lumican (600616), and the matrix protein PRELP (601914). Each of these molecules is present in the extracellular matrix of cartilage, each possesses 10 adjacent LRR regions flanked by disulfide-bonded domains, and each possesses consensus motifs within the LRR regions for N-linked glycosylation.
Grover et al. (1997) cloned a cDNA of the human CHAD gene using PCR-based techniques. The gene encodes a protein of 359 amino acids, of which the first 21 amino acids represent a putative signal peptide sequence. It possesses 11 leucine-rich repeats flanked by cysteine-rich regions. The cDNA has a 5-prime untranslated region of 149 bp, a coding region of 1,080 bp including the stop codon, and a 3-prime untranslated region of 561 bp terminating in a poly(A) tail. The cDNA hybridized with a single messenger RNA of 1.9 kb, which is present in chondrocytes at all ages.
Akhatib et al. (2013) found that CHAD was intact in normal human intervertebral discs (IVDs), but that it was fragmented in adults with IVD degeneration and in damaged discs in adolescent idiopathic scoliosis. The amount of fragmented CHAD correlated with severity of disease, but in all cases, CHAD was specifically cleaved between ile80 and tyr81. Akhatib et al. (2013) found that the CHAD cleavage site generated by the extracellular serine peptidase HTRA1 (602194) was identical to that present in situ. HTRA1 protein was observed in both degenerate adult and adolescent scoliotic samples and was elevated compared with normal disc samples. Akhatib et al. (2013) concluded that HTRA1 plays a role in CHAD fragmentation in degenerating disc diseases.
Grover et al. (1997) determined that the CHAD gene contains 3 exons.
Using a cosmid clone spanning the CHAD gene, Grover et al. (1997) assigned the gene to 17q21.33 by PCR analysis of human/hamster somatic cell hybrids and by fluorescence in situ hybridization.
Akhatib, B., Onnerfjord, P., Gawri, R., Ouellet, J., Jarzem, P., Heinegard, D., Mort, J., Roughley, P., Haglund, L. Chondroadherin fragmentation mediated by the protease HTRA1 distinguishes human intervertebral disc degeneration from normal aging. J. Biol. Chem. 288: 19280-19287, 2013. [PubMed: 23673665] [Full Text: https://doi.org/10.1074/jbc.M112.443010]
Grover, J., Chen, X.-N., Korenberg, J. R., Roughley, P. J. The structure and chromosome location of the human chondroadherin gene (CHAD). Genomics 45: 379-385, 1997. [PubMed: 9344663] [Full Text: https://doi.org/10.1006/geno.1997.4951]
Larsson, T., Sommarin, Y., Paulsson, M., Antonsson, P., Hedbom, E., Wendel, M., Heinegard, D. Cartilage matrix proteins: a basic 36-kDa protein with a restricted distribution to cartilage and bone. J. Biol. Chem. 266: 20428-20433, 1991. [PubMed: 1939097]