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Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases.

ABSTRACT: Collagen alpha-1(III) chain, also known as the alpha 1 chain of type III collagen, is a protein that in humans is encoded by the COL3A1 gene. Three alpha 1 chains are required to form the type III collagen molecule which has a long triple-helical domain. Type III collagen, an extracellular matrix protein, is synthesized by cells as a pre-procollagen. It is found as a major structural component in hollow organs such as large blood vessels, uterus and bowel. Other functions of type III collagen include interaction with platelets in the blood clotting cascade and it is also an important signaling molecule in wound healing. Mutations in the COL3A1 gene cause the vascular type of Ehlers-Danlos syndrome (vEDS; OMIM 130050). It is the most serious form of EDS, since patients often die suddenly due to a rupture of large arteries. Inactivation of the murine Col3a1 gene leads to a shorter life span in homozygous mutant mice. The mice die prematurely from a rupture of major arteries mimicking the human vEDS phenotype. The biochemical and cellular effects of COL3A1 mutations have been studied extensively. Most of the glycine mutations lead to the synthesis of type III collagen with reduced thermal stability, which is more susceptible for proteinases. Intracellular accumulation of this normally secreted protein is also found. Ultrastructural analyses have demonstrated dilated rough endoplasmic reticulum and changes in the diameter of collagen fibers. Other clinical conditions associated with type III collagen are several types of fibroses in which increased amounts of type III collagen accumulate in the target organs.

SUBMITTER: Kuivaniemi H

PROVIDER: S-EPMC6579750 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases.

Kuivaniemi Helena H Tromp Gerard G

Gene 20190507

Collagen alpha-1(III) chain, also known as the alpha 1 chain of type III collagen, is a protein that in humans is encoded by the COL3A1 gene. Three alpha 1 chains are required to form the type III collagen molecule which has a long triple-helical domain. Type III collagen, an extracellular matrix protein, is synthesized by cells as a pre-procollagen. It is found as a major structural component in hollow organs such as large blood vessels, uterus and bowel. Other functions of type III collagen in ...[more]

PMID: 31075413

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Project description:A novel heterozygous mutation of the COL3A1 gene that encodes the alpha 1(III) chains of type III collagen was identified in a family with the acrogeric form of Ehlers-Danlos syndrome type IV (EDS-IV). Cultured dermal fibroblasts produced normal and shortened alpha 1(III) chains. The triple helix of the latter chain was shortened owing to a 33 amino acid deletion of Gly-184 to Pro-216. The corresponding region of cDNA lacked 99 base pairs from nucleotides 1051 to 1149. The deletions corresponded exactly to the normal sequence encoded by exon 17 of the COL3A1 gene. The proband was heterozygous for a T to G transversion at position +2 of intron 17, which resulted in skipping of exon 17. The splicing defect was not corrected by growing the fibroblasts at 33 degrees C and no other splicing variants were identified at 33 or 37 degrees C. The affected brother had the same mutation but his unaffected mother did not. Heterotrimeric type III collagen molecules containing normal and mutant chains were retained within the cell. The mutant homotrimeric molecules were modified and secreted normally and were thermally stable. These normal characteristics of the mutant homotrimers suggested that the loss of ten Gly-Xaa-Yaa triplets (where Gly-Xaa-Yaa is a repetitive amino acid triplet structure in which Xaa and Yaa are other amino acids, proline and hydroxyproline being more common in the Yaa position) did not adversely affect the formation and stability of the triple helix or the structural requirements for secretion. However, the mutant homotrimers were not incorporated into the extracellular matrix of an in vitro model of EDS-IV dermis. The EDS-IV phenotype in this family was probably due to a deficiency in the amount of normal type III collagen available for formation of the heterotypic collagen fibrils of the extracellular matrix. Intracellular and extracellular quality-control mechanisms prevented the incorporation of heterotrimeric and homotrimeric mutant type III collagen molecules into the cross-linked extracellular matrix.

Dataset Information

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases.

Publications

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases.

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