COL6A3

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Collagen, type VI, alpha 3
Protein COL6A3 PDB 1knt.png
PDB rendering based on 1knt.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols COL6A3 ; DKFZp686D23123; DKFZp686K04147; DKFZp686N0262; FLJ34702; FLJ98399
External IDs OMIM120250 MGI88461 HomoloGene37917 GeneCards: COL6A3 Gene
RNA expression pattern
PBB GE COL6A3 201438 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1293 12835
Ensembl ENSG00000163359 ENSMUSG00000048126
UniProt P12111 D3YWD1
RefSeq (mRNA) NM_004369 NM_001243008
RefSeq (protein) NP_004360 NP_001229937
Location (UCSC) Chr 2:
238.23 – 238.32 Mb
Chr 1:
90.77 – 90.84 Mb
PubMed search [1] [2]

Collagen alpha-3(VI) chain is a protein that in humans is encoded by the COL6A3 gene.[1][2][3] This protein is an alpha chain of type VI collagen that aids in microfibril formation.[4] 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.[3][5][6]

Structure[edit]

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.[3]

Function[edit]

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.[3] 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.[4]

Clinical Significance[edit]

Mutations in the type VI collagen genes are associated with Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD).[3][5] 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.[5] A study on UCMD mutations by Zhang et al found only one non-pathogenic mutation in COL6A3.[6] 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.[5] Though high expression levels of COL6A3 have been correlated with obesity and diabetes in mice, this relationship was not observed in humans.[7] Other disorders involving muscle and connective tissue include weakness, joint laxity and contractures, and abnormal skin.[5]

References[edit]

  1. ^ 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. PMID 1339440. 
  2. ^ Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M et al. (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. 
  3. ^ a b c d e "Entrez Gene: COL6A3 collagen, type VI, alpha 3". 
  4. ^ a b 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. 
  5. ^ a b c d e Bushby KM, Collins J, Hicks D (2014). "Collagen type VI myopathies". Advances in Experimental Medicine and Biology 802: 185–99. doi:10.1007/978-94-007-7893-1_12. PMID 24443028. 
  6. ^ a b Zhang YZ, Zhao DH, Yang HP, Liu AJ, Chang XZ, Hong DJ et al. (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. 
  7. ^ McCulloch LJ, Rawling TJ, Sjöholm K, Franck N, Dankel SN, Price EJ et al. (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. PMID 25337653. 

Further reading[edit]

External links[edit]