COL6A3
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesCOL6A3, DYT27, BTHLM1, UCMD1, collagen type VI alpha 3, collagen type VI alpha 3 chain
External IDsOMIM: 120250 MGI: 88461 HomoloGene: 37917 GeneCards: COL6A3
Orthologs
SpeciesHumanMouse
Entrez

1293

12835

Ensembl

ENSG00000163359

ENSMUSG00000048126

UniProt

P12111

n/a

RefSeq (mRNA)

NM_004369
NM_057164
NM_057165
NM_057166
NM_057167

NM_001243008
NM_001243009
NM_009935

RefSeq (protein)

NP_004360
NP_476505
NP_476506
NP_476507
NP_476508

n/a

Location (UCSC)Chr 2: 237.32 – 237.41 MbChr 1: 90.77 – 90.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Collagen alpha-3(VI) chain is a protein that in humans is encoded by the COL6A3 gene.[5][6][7] This protein is an alpha chain of type VI collagen that aids in microfibril formation.[8] As part of type VI collagen, this protein has been implicated in Bethlem myopathy, Ullrich congenital muscular dystrophy (UCMD), and other diseases related to muscle and connective tissue.[7][9][10]

Structure

This gene encodes the alpha 3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha 3 chain of type VI collagen is much larger than the alpha 1 and 2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, found in the amino terminal globular domain of all the alpha chains. In addition to the full length transcript, four transcript variants have been identified that encode proteins with N-terminal globular domains of varying sizes.[7]

Function

The alpha 3 type VI chain has been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components.[7] Microfibril formation has been traced to interactions between its N-terminal subdomain N5 and its C-terminal C5 domain in adjacent type VI collagen monomers.[8]

Clinical significance

Mutations in the type VI collagen genes are associated with Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD).[7][9] Typically, both Bethlem myopathy and autosomal recessive UCMD patients are heterozygous for mutations in the three type VI collagen alpha chains, but only the former exhibit symptoms. Of the three alpha chains, COL6A3 mutations contribute to only 18% of the Bethlem myopathy and UCMD cases.[9] A study on UCMD mutations by Zhang et al found only one non-pathogenic mutation in COL6A3.[10] Nonetheless, knockdown of mutant COL6A3 in patient fibroblast cells using siRNA has successfully improved cellular deposition of type VI collagen in autosomal dominant UCMD, and may become a promising treatment for it.[9] Though high expression levels of COL6A3 have been correlated with obesity and diabetes in mice, this relationship was not observed in humans.[11] Other disorders involving muscle and connective tissue include weakness, joint laxity and contractures, and abnormal skin.[9]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000163359 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000048126 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Zanussi S, Doliana R, Segat D, Bonaldo P, Colombatti A (Nov 1992). "The human type VI collagen gene. mRNA and protein variants of the alpha 3 chain generated by alternative splicing of an additional 5-end exon". The Journal of Biological Chemistry. 267 (33): 24082–9. doi:10.1016/S0021-9258(18)35949-0. PMID 1339440.
  6. ↑ Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P (Jun 2002). "Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy". American Journal of Human Genetics. 70 (6): 1446–58. doi:10.1086/340608. PMC 419991. PMID 11992252.
  7. 1 2 3 4 5 "Entrez Gene: COL6A3 collagen, type VI, alpha 3".
  8. 1 2 Lamandé SR, Mörgelin M, Adams NE, Selan C, Allen JM (Jun 2006). "The C5 domain of the collagen VI alpha3(VI) chain is critical for extracellular microfibril formation and is present in the extracellular matrix of cultured cells". The Journal of Biological Chemistry. 281 (24): 16607–14. doi:10.1074/jbc.M510192200. PMID 16613849.
  9. 1 2 3 4 5 Bushby KM, Collins J, Hicks D (2014). "Collagen Type VI Myopathies". Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology. Vol. 802. pp. 185–99. doi:10.1007/978-94-007-7893-1_12. ISBN 978-94-007-7892-4. PMID 24443028.
  10. 1 2 Zhang YZ, Zhao DH, Yang HP, Liu AJ, Chang XZ, Hong DJ, Bonnemann C, Yuan Y, Wu XR, Xiong H (May 2014). "Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy". World Journal of Pediatrics. 10 (2): 126–32. doi:10.1007/s12519-014-0481-1. PMID 24801232. S2CID 38175712.
  11. ↑ McCulloch LJ, Rawling TJ, Sjöholm K, Franck N, Dankel SN, Price EJ, Knight B, Liversedge NH, Mellgren G, Nystrom F, Carlsson LM, Kos K (Jan 2015). "COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity". Endocrinology. 156 (1): 134–46. doi:10.1210/en.2014-1042. hdl:10871/26502. PMID 25337653.

Further reading

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