COL1A2
| Type I collagen, alpha 2 | ||
|---|---|---|
| other names |
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| Properties of human protein | ||
| Mass / length primary structure | 129,314 daltons / 1,366 amino acids (isoform 1)
19,869 daltons / 179 amino acids (isoform 2) 115,329 daltons / 1,039 amino acids (isoform 3) |
|
| Isoforms | 3 | |
| Identifier | ||
| Gene names | COL1A2 OI4 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | Eukaryotes | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 1278 | 12843 |
| Ensemble | ENSG00000164692 | ENSMUSG00000029661 |
| UniProt | P08123 | P11087 |
| Refseq (mRNA) | NM_000089 | NM_007743 |
| Refseq (protein) | NP_000080 | NP_031769 |
| Gene locus | Chr 7: 94.39 - 94.43 Mb | Chr 6: 4.5 - 4.54 Mb |
| PubMed search | 1278 |
12843
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Type I collagen, alpha 2 , also known as alpha-2 type I collagen , is a protein encoded by the COL1A2 gene in the human organism . In mammals, collagen type I, a fibrillar collagen , is the most common type of collagen and occurs in skin , tendons , fascia , bones , connective tissue , cartilage , vessels , internal organs, sclera and dentin . In particular, COL1A2 is most strongly expressed in smooth muscle , adipocytes and the uterus .
Gene structure
COL1A2 is encoded by 52 exons . The exons are distributed as follows: six are located on the N -terminal propeptide, 42 on the alpha-2 (I) chain and four on the C -terminal propeptide. The gene is located on the long chromosome arm (q arm) on chromosome band 7q21.3 of chromosome 7 .
COL1A2 is increasingly located in the extracellular space . The gene is also present in the cell membrane , in the nucleus , in the cytoskeleton and in the lysosome .
function
Type I collagen has a triple helix as a tertiary structure . It contains two Pro-α1 (I) polypeptide chains , which are encoded by the COL1A1 gene, and a Pro-α2 (I) chain, which is encoded by the gene described here, in order to be able to produce a type I procollagen. This must procollagen outside the cell processed are. The subsequent cross-linking results in a very strong and mature collagen fibril type I. Mutations in this gene are associated with the hereditary disease osteogenesis imperfecta type I-IV, the Ehlers-Danlos syndrome (anthrochalasia and classic type), idiopathic juvenile osteoporosis and the atypical marfan Syndrome associated.
Interaction with other proteins
COL1A2 interacts with a total of 27 proteins:
Clinical Significance
Mutations in the COL1A2 gene could cause the following diseases:
- Ehlers-Danlos syndrome, arthrochalasia type: In this syndrome 18 amino acids are deleted . The deleted segment corresponds to the N -terminal telopeptide, which is encoded by six exons of the pro-α2 (I) collagen chain. A sequencing a specially prepared cDNA confirmed the presence of two distinct variants of pro-alpha-2 (I) mRNAs: one variant is normal, while the other has a gap, as a sequence of exon 6 is absent. Limited sequencing of genomic cDNA clones shows that a conservative substitution in the seventh codon of exon 6 has taken place in one of the pro-alpha-2 (I) alleles . The codon GAC was substituted for GAT and a transition took place, with adenine being substituted for guanine at position 1 of intron 6. This leads to a shortened pro-alpha-2 (I) collagen mRNA. Because of this point mutation , it results in dysfunction of the exon 5 and 7 sequence.
- Osteogenesis imperfecta type I (OI1): The reason for this is a G - A transition in the COL1A2 gene, which results in a substitution of cysteine for glycine at position 246 of the alpha-2 (I) chain. These mutated type I collagen molecules already denature at low temperatures.
- Osteogenesis imperfecta type II (OI2): With OI2 a single nucleotide polymorphism could be detected in the mRNA. This region of the mRNA was amplified using the polymerase chain reaction . A heterozygous point mutation from guanine to cytosine in the base pair 1,774 of the collagen-alpha-2 (I) -mRNA results in a substitution of glycine with arginine at position 457 of the helix. This mutation leads to a reduced secretion of procollagen and a destabilization of the helix, which was demonstrated by the reduced thermal stability.
- Osteogenesis imperfecta type III (OI3): OI3 is caused by a point mutation, more precisely a transversion . A GT transversion takes place at nucleotide position 1121, which leads to the amino acid substitution Gly238Cys.
- Osteogenesis imperfecta type IV (OI4): OI4 is caused by a GC transversion at position 1406 in the COL1A2 gene, which results in a Gly379Ala substitution.
- Marfan syndrome: this syndrome are detected two different variants of the alpha-2 (I) chain: A is normal, wherein the other chain abnormal an insertion of 20 amino acids at the N -terminal has the end of the propeptide and thus a higher molecular weight has .
Individual evidence
- ↑ a b c d e COL1A2. In: GeneCards (English).
- ^ Wouter de Wet, Michael Bernard: Organization of the human pro-alpha-2 (I) collagen gene . (PDF; 3.01 MB) In: The Journal of Biological Chemistry (jbc) . 262, No. 33, November 25, 1987, pp. 16032-16036.
- ↑ COL1A1. In: Online Mendelian Inheritance in Man . (English)
- ↑ UniProt P08123
- ^ D. Weil, M. D'Alessio, F. Ramirez, DR Eyre: Structural and functional characterization of a splicing mutation in the pro-alpha 2 (I) collagen gene of an Ehlers-Danlos type VII patient. In: The Journal of biological chemistry. Volume 265, Number 26, September 1990, pp. 16007-16011, PMID 2394758 .
- ↑ RJ Wenstrup, AW Shrago-Howe, LW Lever, CL Phillips, PH Byers, DH Cohn: The effects of different cysteine for glycine substitutions within alpha 2 (I) chains. Evidence of distinct structural domains within the type I collagen triple helix. In: The Journal of biological chemistry. Volume 266, Number 4, February 1991, pp. 2590-2594, PMID 1990009 .
- ↑ JF Bateman, I. Moeller, M. Hannagan, D. Chan, WG Cole: Lethal perinatal osteogenesis imperfecta due to a type I collagen alpha 2 (I) Gly to Arg substitution detected by chemical cleavage of an mRNA: cDNA sequence mismatch. In: Human mutation. Volume 1, Number 1, 1992, pp. 55-62, doi : 10.1002 / humu.1380010109 , PMID 1284475 .
- ^ T. Trummer, R. Brenner, W. Just, W. Vogel, I. Kennerknecht: Recurrent mutations in the COL1A2 gene in patients with osteogenesis imperfecta. In: Clinical genetics. Volume 59, Number 5, May 2001, pp. 338-343, PMID 11359465 .
- ^ MT Johnson, S. Morrison, S. Heeger, S. Mooney, PH Byers, NH Robin: A variant of osteogenesis imperfecta type IV with resolving kyphomelia is caused by a novel COL1A2 mutation. In: Journal of medical genetics. Volume 39, Number 2, February 2002, pp. 128-132, PMID 11836364 , PMC 1735034 (free full text).
- ↑ PH Byers, RC Siegel, KE Peterson, DW Rowe, KA Holbrook, LT Smith, YH Chang, JC Fu: Marfan syndrome: abnormal alpha 2 chain in type I collagen. In: Proceedings of the National Academy of Sciences . Volume 78, Number 12, December 1981, pp. 7745-7749, PMID 6950413 , PMC 349347 (free full text).