HGNC Approved Gene Symbol: COL21A1
Cytogenetic location: 6p12.1 Genomic coordinates (GRCh38) : 6:56,056,590-56,394,128 (from NCBI)
COL21A1 belongs to the family of fibril-associated collagens with an interrupted triple helix (FACIT collagens). FACIT collagens bind to the surface of collagen fibrils and link them with other matrix molecules (Tuckwell, 2002).
By searching a database for genes encoding proteins with a von Willebrand factor (VWF; 613160) type A (VWFA) domain, Fitzgerald and Bateman (2001) identified COL21A1. The deduced 957-amino acid protein has a calculated molecular mass of 99 kD. It contains an N-terminal signal sequence, followed by a VWFA domain, a thrombospondin (see THSB1; 188060) domain, and 2 C-terminal collagen domains separated by a short interruption. COL21A1 has 2 putative N-glycosylation sites and several potential O-glycosylation sites, and the VWFA domain has a putative MIDAS motif for ion binding. Northern blot analysis detected a 4.2-kb COL21A1 transcript in heart, placenta, jejunum, skeletal muscle, colon, kidney, liver, and lung. An additional 2.4-kb transcript was detected in skeletal muscle and heart, with the smaller transcript predominating in heart. Little to no expression was detected in brain, spleen, thymus, and peripheral leukocytes. RNA dot blot analysis revealed highest COL21A1 expression in adult and fetal heart, placenta, stomach, jejunum, skeletal muscle, kidney, lung, pancreas, and lymph node. COL21A1 expression in heart was higher in the right ventricle and atrium than in the left ventricle and atrium.
Chou and Li (2002) identified 2 splice variants of the COL21A1 gene that differed in their 5-prime UTRs. Northern blot analysis detected a major transcript of 4.4-kb in fetal heart and adult aorta, but not in any other adult heart regions examined. RT-PCR showed that expression of COL21A1 was significantly more abundant in fetal brain, heart, and liver than in the adult counterparts. In other adult tissues, expression was high in trachea, testis, uterus, and placenta. In situ hybridization of cardiovascular tissues detected COL21A1 in the extracellular matrix component of blood vessel walls. COL21A1 was expressed in the cytoplasm of cultured human aortic smooth muscle cells, but not cultured aortic endothelial cells.
Chou and Li (2002) found that serum withdrawal nearly abolished expression of COL21A1 by cultured human aortic smooth muscle cells. Exposure of these cells to PDGF-BB (see 190040) in the presence of serum increased COL21A1 mRNA expression.
Fitzgerald and Bateman (2001) determined that the COL21A1 gene contains 30 exons and spans about 190 kb. Chou and Li (2002) determined that the COL21A1 gene spans 337 kb and contains 31 exons, including 2 alternatively spliced first exons, 1 and 1a. No TATAA or CCAAT boxes are present in the 5-prime noncoding regions upstream of exons 1 and 1a.
Using radiation hybrid analysis, Fitzgerald and Bateman (2001) mapped the COL21A1 gene to chromosome 6p12-p11. By genomic sequence analysis, Chou and Li (2002) mapped the COL21A1 gene to chromosome 6p12.3-p11.2.
Chou, M.-Y., Li, H.-C. Genomic organization and characterization of the human type XXI collagen (COL21A1) gene. Genomics 79: 395-401, 2002. [PubMed: 11863369] [Full Text: https://doi.org/10.1006/geno.2002.6712]
Fitzgerald, J., Bateman, J. F. A new FACIT of the collagen family: COL21A1. FEBS Lett. 505: 275-280, 2001. [PubMed: 11566190] [Full Text: https://doi.org/10.1016/s0014-5793(01)02754-5]
Tuckwell, D. Identification and analysis of collagen alpha-1(XXI), a novel member of the FACIT collagen family. Matrix Biol. 21: 63-66, 2002. [PubMed: 11827793] [Full Text: https://doi.org/10.1016/s0945-053x(01)00176-7]