COL2A1

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Type II collagen, alpha 1
Type II collagen, alpha 1
Ribbon model of the protein COL2A1 according to PDB  3HR2
other names
  • Alpha-1 type II collagen
  • Collagen II, alpha-1 polypeptide
  • Collagen alpha-1 (II) chain

Existing structural data : 2FSE , 2SEB

Properties of human protein
Mass / length primary structure 141,785 daltons / 1,487 amino acids (isoform 1)

170,385 daltons / 1,535 amino acids (isoform 2)

170,274 daltons / 1,534 amino acids (isoform 3)

131,313 daltons / 1,535 amino acids (isoform 4)

Isoforms 4th
Identifier
Gene names COL2A1 ANFH, AOM, SEDC, STL1
External IDs
Occurrence
Parent taxon Eukaryotes
Orthologue
human House mouse
Entrez 1280 12824
Ensemble ENSG00000139219 ENSMUSG00000022483
UniProt P02458 P28481
Refseq (mRNA) NM_001844 NM_001113515
Refseq (protein) NP_001835 NP_001106987
Gene locus Chr 12: 47.97 - 48 Mb Chr 15: 97.98 - 98 Mb
PubMed search 1280 12824

Type II collagen, alpha 1 , also known as alpha-1 type II collagen , is a protein encoded by the COL2A1 gene in the human organism . In mammals, type II collagen, a fibrillar collagen , functions as a structural protein of the hyaline and elastic cartilage. COL2A1 is particularly strongly expressed in the vitreous humor , in the nucleus pulposus of the intervertebral disc and in the inner ear .

history

Elisabeth Weiss, former C3 professor for molecular human genetics at the Ludwig Maximilians University in Munich , described an isolated collagen gene in a 40 kb long cosmid clone (cosHco11), which has homologies with the nucleotide sequence of alpha-1 (I) - Gens , but was obviously a different gene.

In 1984, the American geneticist Ellen Solomon, a molecular biological test method for the in somatic cells derived DNA by which to Southern blot to investigate calls to the gene sequence of yet unidentified gene. It turned out that the gene is on chromosome 17 and that there was no syntany between COL1A2 and COL1A1 .

Francis Michael Pope, Welsh clinical geneticist, found in 1984 a 300 bp deletion that this mutated gene caused Ehlers-Danlos syndrome (classic type). The deletion was discovered near the 3 'end of the gene. This mutated gene was also discovered in four babies suffering from the lethal osteogenesis imperfecta type III.

Charles Strom, American geneticist, confirmed in 1984 the abnormality of this gene (which has since been referred to as COL2A1 ) in a mutation using the example of achondroplasia and congenital spondyloepiphyseal dysplasia .

In 1985, human geneticist Bryan Sykes discovered that this gene codes for the alpha subunit of collagen in cartilage. A polymorphism was also found in this gene, which was often found in Indians .

Gene structure

COL2A1 contains a total of 67 exons . The gene is located on the long chromosome arm (q arm) on chromosome band 12q13.11 of chromosome 12 .

function

Type II collagen is essential for cartilage tissue. It is also relevant for the normal embryonic development of the skeleton, linear growth and the ability of the cartilage tissue to withstand compressive forces. Mutations in this gene are primarily associated with achondrogenesis type II , skeletal dysplasia , arthrosis , congenital spondyloepiphyseal dysplasia , Kniest dysplasia , Stickler syndrome type I, spondyloepimetaphyseal dysplasia type Strudwick and other diseases. COL2A1 contains a calcium-binding protein called chondrocalcin that forms the C -terminal propeptide of this collagen molecule. If there are defects in the processing of the chondrocalcin, it can lead to achondroplasia.

Interaction with other proteins

COL2A1 interacts with a total of 23 proteins:

Clinical Significance

Mutations in the COL2A1 gene could cause the following diseases:

  • Achondrogenesis Type II : In this type, an abnormal pro-alpha-1 (II) chain can be detected that interferes with the production of a type II collagen fibril. This is achieved by a single nucleotide polymorphism caused, which, with the result that the amino acid glycine to serine at nucleotide position 942 substituted is.
  • Dysplasia, epiphyseal multiple, type Beighton : This is caused by a heterozygous C - T - transversion at nucleotide position 2503 of exon 39 of the COL2A1 gene. This in turn results in a substitution of arginine for cysteine at position 704, which occurs frequently at the X position of the Gly-XY triplet of the collagen triple helix.
  • Hypochondrogenesis : Cause is a GSM A - Transition , which leads to a substitution of glycine for serine at position 943 or 574th This affects the intercellular transport and secretion of the collagen molecules and separates the collagen fibrils.
  • Kniest Dysplasia : An abnormally short pro-alpha I (II) chain is produced. It comes to networking with normal length collagen chains. The result is that type II collagen molecules are shorter than they normally are.
  • Congenital spondyloepiphyseal dysplasia : Congenital spondyloepiphyseal dysplasia can be caused by various mutations in the COL2A1 gene. These mutations can result in an incorrect substitution of an amino acid in the pro-alpha1 (II) chain, resulting in the production of an abnormally shortened pro-alpha1 (II) chain.
  • Platyspondylitic dysplasia type Torrance : Less than ten mutations in the COL2A1 gene have been identified with platyspondylitic dysplasia type Torrance. Most of these mutations are caused by single nucleotide polymorphisms in the pro-alpha1 (II) chain. These COL2A1 mutations lead to an abnormal variant of a pro-alpha1 (II) chain, which cannot be integrated into type II collagen fibrils. As a result, the cells produce less type II collagen. The abnormal pro-alpha1 (II) chain continues to build up in cartilage cells (chondrocytes). As a result, bone development is disturbed, resulting in skeletal abnormalities.

Other diseases that can be triggered by mutations in the COL2A1 gene :

Animal model

In a transgenic mouse that has a partially deleted human COL2A1 gene, achondroplasia can be diagnosed, which can lead to a disproportionate short stature. Characteristics are thick and short extremities, cranial swellings, short proboscis-like nose, split palate, and delayed bone mineralization.

Individual evidence

  1. ↑ a b COL2A1. In: GeneCards (English).
  2. ↑ EH Weiss, KS Cheah: Isolation and characterization of a human collagen alpha 1 (I) -like gene from a cosmid library . In: National Center for Biotechnology Information (NCBI) (Ed.): PubMed . March 25, 1982. PMID 6281728 .
  3. ↑ a b c COL2A1.  In: Online Mendelian Inheritance in Man . (English)
  4. ↑ Pope FM, Cheah KS: Lethal osteogenesis imperfecta congenita and a 300 base pair gene deletion for an alpha 1 (I) -like collagen . In: National Center for Biotechnology Information (NCBI) (Ed.): PubMed . February 11, 1984. PMID 6419953 .
  5. ↑ CM Strom: Achondroplasia due to DNA insertion into the type II collagen gene . In: Nature (Ed.): Patriatric Research . 1984. doi : 10.1203 / 00006450-198404001-00800 .
  6. ^ B. Sykes, R. Smith: Exclusion of the alpha-1 (II) cartilage collagen gene as the mutant locus in type IA osteogenesis imperfecta . (PDF; 534 kB) In: British Medical Journal (BMJ) (Ed.): Journal of Medical Genetics . 1984.
  7. ↑ a b COL2A1 collagen, type II, alpha 1 Homo sapiens (human). In: National Center for Biotechnology Information (NCBI) , accessed December 23, 2015 .
  8. ↑ UniProt P02458
  9. ↑ COL2A1. In: Orphanet (Rare Disease Database).