Collagen, type XXI, alpha 1
| COL21A1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | COL21A1, collagen, type XXI, alpha 1, COLA1L, dJ682J15.1, dJ708F5.1, FP633, collagen type XXI alpha 1, collagen type XXI alpha 1 chain | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 610002; GeneCards: COL21A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Collagen alpha-1(XXI) chain is a protein that in humans is encoded by the COL21A1 gene.[3] It is the alpha chain of type XXI collagen, a collagen belonging to the FACIT collagen family (fibril-associated collagens with interrupted triple helices).[4] Type XXI collagen is an extracellular matrix component that is found in tissues containing type I collagen and is linked to the assembly and maintenance of the extracellular matrix and is also a component of blood vessel walls, where it is secreted by smooth-muscle cells and may contribute to extracellular matrix assembly of the vascular network during blood vessel formation.[5][6]
Gene
In humans, COL21A1 is located on the short arm of chromosome 6 at band 6p12.3–p11.2.[3][5] The gene spans approximately 337 kb of genomic DNA and contains 31 exons; its 5′-untranslated exons (exon 1 and exon 1a) are alternatively spliced, and alternative splicing of the gene gives rise to multiple transcript variants.[5][6] The exon–domain organization of COL21A1 resembles that of other genes encoding FACIT collagens.[5]
Protein
The human collagen alpha-1(XXI) chain is a 957-amino acid protein.[7] As a FACIT collagen, it has a domain organization consisting of an N-terminal signal peptide followed by a single von Willebrand factor A (VWA) domain, a thrombospondin N-terminal (TSPN) domain, and a collagen triple-helical region that is interrupted by short non-collagenous segments.[4][7] This interrupted triple-helical structure is the defining feature of the FACIT subfamily, whose members associate with the surfaces of major fibril-forming collagens rather than forming fibrils on their own.[4] The mature protein is secreted into the extracellular space and localizes to the extracellular matrix.[7]
Tissue distribution
COL21A1 is expressed in a broad range of tissues, including skin, trachea, testis, uterus, placenta, lymph node, stomach and the walls of blood vessels, generally overlapping the distribution of type I collagen.[4][7][8] Among these, relative expression is highest in lymph node, jejunum, pancreas, stomach, trachea, testis, uterus and placenta; moderate levels are found in brain, colon, lung, prostate, spinal cord, salivary gland and vascular smooth-muscle cells; and expression is weak in heart, liver, kidney, bone marrow, spleen and thymus.[7]
COL21A1 expression is developmentally regulated, being higher at fetal stages than in the corresponding adult tissues. In a comparison of matched human tissues, COL21A1 transcripts were approximately 2.7-, 22- and 30-fold more abundant in fetal brain, heart and liver, respectively, than in their adult counterparts, suggesting a role in developmental processes.[5] In cultured aortic smooth-muscle cells, expression of COL21A1 is stimulated by platelet-derived growth factor (PDGF).[5] Its presence in the walls of blood vessels, where it is produced by smooth-muscle cells, was noted in the original characterization of the gene.[5]
Type XXI collagen is also expressed in human skin, where it is a low-abundance component of the dermal extracellular matrix, as detected by quantitative proteomics of healthy skin.[8] In a time-resolved proteomic atlas of the developing skin dermis, type XXI collagen was among the fibril-associated collagens whose abundance declined progressively with age over the human lifespan.[9]
Clinical significance
A genetic association study of four large extended Malay families reported that a decrease in COL21A1 copy number (reduced gene dosage) co-segregated with nonsyndromic cleft lip and/or palate, identifying COL21A1 (together with TOX3) as a candidate susceptibility gene for the condition.[10] This is a single primary study, and a causal role for COL21A1 in cleft lip/palate has not been established.[10]
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000124749 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 1 2 "COL21A1 collagen, type XXI, alpha 1". Entrez Gene: COL21A1. United States National Center for Biotechnology Information.
- 1 2 3 4 Fitzgerald J, Bateman JF (September 2001). "A new FACIT of the collagen family: COL21A1". FEBS Letters. 505 (2): 275–280. doi:10.1016/S0014-5793(01)02754-5. PMID 11566190.
- 1 2 3 4 5 6 7 Chou MY, Li HC (March 2002). "Genomic organization and characterization of the human type XXI collagen (COL21A1) gene". Genomics. 79 (3): 395–401. doi:10.1006/geno.2002.6712. PMID 11863369.
- 1 2 "COL21A1 collagen type XXI alpha 1 chain [Homo sapiens] – Gene". RefSeq. National Center for Biotechnology Information. Retrieved 2026-07-23.
- 1 2 3 4 5 "Q96P44 · COLL_HUMAN Collagen alpha-1(XXI) chain". UniProt. Retrieved 2026-07-23.
- 1 2 Dyring-Andersen B, Løvendorf MB, Coscia F, Santos A, Møller LB, Colaço AR, Niu L, Bzorek M, Doll S, Andersen JL, Clark RA, Skov L, Teunissen MB, Mann M (November 2020). "Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin". Nature Communications. 11 (1) 5587. doi:10.1038/s41467-020-19383-8. PMC 7645789. PMID 33154365.
- ↑ Li M, Li X, Liu B, Lv L, Wang W, Gao D, Zhang Q, Jiang J, Chai M, Yun Z, Tan Y, Gong F, Wu Z, Zhu Y, Ma J, Leng L (2021). "Time-Resolved Extracellular Matrix Atlas of the Developing Human Skin Dermis". Frontiers in Cell and Developmental Biology. 9 783456. doi:10.3389/fcell.2021.783456. PMC 8661536. PMID 34901026.
- 1 2 Mohamad Shah NS, Sulong S, Wan Sulaiman WA, Halim AS (May 2019). "Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate". Molecular Genetics & Genomic Medicine. 7 (5) e635. doi:10.1002/mgg3.635. PMC 6503016. PMID 30924295.
Further reading
- Fitzgerald J, Bateman JF (September 2001). "A new FACIT of the collagen family: COL21A1". FEBS Letters. 505 (2): 275–280. doi:10.1016/S0014-5793(01)02754-5. PMID 11566190.
- Chou MY, Li HC (March 2002). "Genomic organization and characterization of the human type XXI collagen (COL21A1) gene". Genomics. 79 (3): 395–401. doi:10.1006/geno.2002.6712. PMID 11863369.