COL4A1

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Type IV collagen, alpha 1
Type IV collagen, alpha 1
Ribbon model of the COL4A1 protein according to PDB  1LI1
other names
  • Alpha 1 Type IV Collagen
  • Collagen Alpha-1 (IV) chain
  • Type IV collagen alpha-1 chain
Properties of human protein
Mass / length primary structure 160,615 daltons / 1,669 amino acids
Isoforms 2
Identifier
Gene names COL4A1; I; BSVD; RATOR; PORES 1
External IDs
Occurrence
Parent taxon Euteleostomi
Orthologue
human House mouse
Entrez 1282 12826
Ensemble ENSG00000187498 ENSMUSG00000031502
UniProt P02462 P02463
Refseq (mRNA) NM_001303110 NM_009931
Refseq (protein) NP_001290039.1 NP_034061.2
Gene locus Chr 13: 110.15 - 110.31 Mb Chr 8: 11.2 - 11.31 Mb
PubMed search 1282 12826

Type IV collagen, alpha 1 , also known as alpha-1 type IV collagen , is a network-forming collagen that is encoded by the COL4A1 gene in the human organism . Together with two other α-type IV collagens (α2 to α6) it forms a trimer, so-called α-chains, which in turn form the actual type IV collagens. Type IV collagen proteins are integral parts of the basement membrane , more precisely the lamina densa . For the most part, it is expressed in the brain and placenta .

history

Edward I. Solomon et al . found out in 1985 that with the help of a cloned gene as a gene probe for the Southern blot, DNA from a panel of cross-species somatic cell hybrids can be assigned to the gene COL4A1 and localized on the 13th chromosome . In the same year, Pihlajaniemi et al . a dual laser , with the chromosomes already sorted, and the dot blot analysis method to assign a genomic DNA sequence to the gene coding for COL4A1 on the 13th chromosome.

Using in situ hybridization , Boyd et al . found out in 1986 that the gene was at the end of the long chromosome arm of the 13th chromosome. Southern blot and dot blot showed that these genomic sequences are only present once in each haploid genome. In the same year, Emanuel et al . assign the COL4A1 gene to the telomeric region 13q (13q34). Bowcock et al . found that the COL4A1 gene locus is linked to the D13S3 locus, which in turn could be assigned to the gene locus 13q33-q34 by in situ hybridization. The maximum LOD score was 16.5 with ϑ = 0.01. Using pulsed field gel electrophoresis and with rarely available restriction enzymes , Cutting et al . demonstrate that the genes COL4A1 and COL4A2 are no more than 400 kb apart .

Bowcock et al . found in 1988 that the probability of coupling between COL4A1 and COL4A2 is approx. 2.8% with a LOD score of 19.98. This lack of coupling between the two genes gives rise to an inconsistency with a relatively high level of recombination between the two loci . In addition, Cutting et al . prove in the same year that the two genes are located within a 340 kb region, the 3 'end of COL4A2 and the 5' region of COL4A1 being at least 100 kb apart, but not more than 160 kb can.

In 1995 Koizumi et al . Interspecific and subspecific mapping panels to locate the COL4A1 gene on the centromeric region of chromosome 8 of a mouse. The Stuart-Prower factor is localized in the same region. Accordingly, a new homology of syntany between the 8th chromosome of a mouse and the 13th chromosome of humans had to be defined.

Gene structure

COL4A1 and COL4A2 share a common bidirectional promoter and the adjacent 5 'regions of these two genes overlap. COL4A1 contains a total of 52 coding exons.

Protein structure

With the help of Fourier transform ion cyclotron resonance mass spectrometry and nuclear magnetic resonance spectroscopy , the binding relationships of the COL4A1 protein could be explained. It was found that the sulfimide bond (-S = N-) cross- links the amino acids hydroxylysine -211 and methionine -93 from adjacent promoters. This bond, the nitrogen-analog of a sulfoxide , due to the divergence of the strains of animals of the sponges and anemones in response to the mechanical stress during the Metazoa -Evolution. In addition, the protein has an N -terminal 7S domain, a triple helix-forming collagenous domain and a C -terminal non-collagenous domain.

function

It acts as part of a heterotrimer and interacts with other extracellular matrix components, such as B. Perlecan , proteoglycans and laminins . In addition, proteolytic cleavage of a non-collagenous C -terminal domain leads to a biologically active fragment known as arrest , which is used as a tumor suppressor and contributes to antiangiogenesis . The protein specifically inhibits endothelial cell proliferation and cell migration . It also inhibits the expression of HIF1A , ERK1 / 2 and the activation of p38 MAPK . The protein also functions as a ligand for ITGA1 and ITB1 .

interaction

COL4A1 can interact with two of the other five collagen IV proteins to form collagen α chains. These are:

Clinical Significance

Mutations in the COL4A1 gene could cause the following diseases:

Individual evidence

  1. ↑ a b c UniProt P02462
  2. ↑ COL4A1. In: GeneCards (English).
  3. ↑ E. Solomon, LR Hiorns, N. Spurr, M. Kurkinen, D. Barlow, BLM Hogan, R. Dalgleish: Chromosomal assignments of the genes coding for human types II, III and IV collagen: a dispersed gene family . (PDF) In: Proc Natl Acad Sci USA . 82, No. 10, May 1985, pp. 3330-3334. PMID 2987919 .
  4. ↑ T. Pihlajaniemi, K. Tryggvason, J. Myers, JC, M. Kurkinen, R. Lebo, M.-C. Cheung, DJ Prockop, CD Broyd: cDNA clones coding for the pro-alpha1 (IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain . (PDF) In: J Biol Chem . 260, No. 12, June 25, 1985, pp. 7681-7687. PMID 2581969 .
  5. ↑ CD Boyd, K. Weliky, S. Toth-Fejel, SB Deak, AM Christiano, JW Mackenzie, LJ Sandell, K. Tryggvason, E. Magenis: The single copy gene coding for human alpha-1 (IV) procollagen is located at the terminal end of the long arm of chromosome 13 . In: Hum Genet . 74, No. 2, October 1986, pp. 121-125. PMID 3770740 .
  6. ↑ BS Emanuel, BT Sellinger, LJ Gudas, JC Myers: Localization of the human procollagen alpha 1 (IV) gene to chromosome 13q34 by in situ hybridization . In: Am J Hum Genet. . 38, No. 1, January 1986, pp. 38-44. PMID 3753820 .
  7. ↑ AM Bowcock, JM Hebert, AM Christiano, E. Wijsman, LL Cavalli-Sforza, CD Boyd: The pro alpha 1 (IV) collagen gene is linked to the D13S3 locus at the distal end of human chromosome 13q . In: Cytogenet Cell Genet . 45, No. 3-4, 1987, pp. 234-236. PMID 2891465 .
  8. ↑ GR Cutting, HH Kazazian, Jr., SE Antonarakis, PD Killen, Y. Yamada, CA Francomano: Macrorestriction analysis maps COL4A1 and COL4A2 collagen genes within a 400 kb region on chromosome 13q34. (Abstract) . In: Am. J. Hum. Genet . 41, 1987.
  9. ↑ AM Bowcock, JM Hebert, E. Wijsman, I. Gadi, LL Cavalli-Sforza, CD Boyd: High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q . In: Proc Natl Acad Sci USA . 85, No. 8, April 1988, pp. 2701-2705. PMID 2895928 .
  10. ^ GR Cutting, HH Kazazian, Jr., SE Antonarakis, PD Killen, Y. Yamada, CA Francomano: Macrorestriction mapping of COL4A1 and COL4A2 collagen genes on human chromosome 13q34 . In: Genomics . 3, No. 3, October 1988, pp. 256-263. PMID 3224982 .
  11. ↑ T. Koizumi, E. Hendel, PA Lalley, M.-BN Tchetgen, JH Nadeau: Homologs of genes and anonymous loci on human chromosome 13 map to mouse chromosomes 8 and 14 . In: Mammalian Genome . 6, No. 4, April 1995, pp. 263-268. PMID 7613031 .
  12. ↑ E. Poschl, R. Pollner, K. Kuhn: The genes for the alpha 1 (IV) and alpha 2 (IV) chains of human basement membrane collagen type IV are Arranged head-to-head and separated by a bidirectional promoter of unique structure . In: EMBO J . 7, No. 9, September 1988, pp. 2687-2695. PMID 2846280 .
  13. ^ R. Soininen, M. Huotari, SL Hostikka, DJ Prockop, K. Tryggvason: The structural genes for alpha 1 and alpha 2 chains of human type IV collagen are divergently encoded on opposite DNA strands and have an overlapping promoter region . In: J Biol Chem . 263, No. 33, November 25, 1988, pp. 17217-17220. PMID 3182844 .
  14. ^ E. Plaisier, Z. Chen, F. Gekeler, S. Benhassine, K. Dahan, B. Marro S. Alamowitch, M. Paques, P. Ronco: Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3 [IV] domain . In: Am J Med Genet A . 152A, No. 10, October 2010, pp. 2550-2555. doi : 10.1002 / ajmg.a.33659 . PMID 20818663 .
  15. ↑ R. Vanacore, A. JL Ham, M. Vöhler, CR Sanders, TP Conrads, TD Veenstra, KB Sharpless, PE Dawson, BG Hudson: A sulfilimine bond Identified in collagen IV . In: Science . 325, No. 5945, September 4, 2009, pp. 1230-1234. doi : 10.1126 / science.1176811 . PMID 19729652 .
  16. ↑ a b GeneID 1282
  17. ↑ COL4A1.  In: Online Mendelian Inheritance in Man . (English)
  18. ↑ Mutations in the COL4A1 gene. In: Orphanet. Retrieved July 11, 2016 .