COL6A3

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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 ; DYT27
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:
237.32 – 237.41 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, 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. 
  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, 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. 
  7. ^ 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. PMID 25337653. 

Further reading[edit]

  • Lampe AK, Bushby KM (Sep 2005). "Collagen VI related muscle disorders". Journal of Medical Genetics 42 (9): 673–85. doi:10.1136/jmg.2002.002311. PMC 1736127. PMID 16141002. 
  • Chu ML, Zhang RZ, Pan TC, Stokes D, Conway D, Kuo HJ, Glanville R, Mayer U, Mann K, Deutzmann R (Feb 1990). "Mosaic structure of globular domains in the human type VI collagen alpha 3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and aprotinin type protease inhibitors". The EMBO Journal 9 (2): 385–93. PMC 551678. PMID 1689238. 
  • Chu ML, Conway D, Pan TC, Baldwin C, Mann K, Deutzmann R, Timpl R (Dec 1988). "Amino acid sequence of the triple-helical domain of human collagen type VI". The Journal of Biological Chemistry 263 (35): 18601–6. PMID 3198591. 
  • Weil D, Mattei MG, Passage E, N'Guyen VC, Pribula-Conway D, Mann K, Deutzmann R, Timpl R, Chu ML (Mar 1988). "Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen". American Journal of Human Genetics 42 (3): 435–45. PMC 1715162. PMID 3348212. 
  • Chu ML, Mann K, Deutzmann R, Pribula-Conway D, Hsu-Chen CC, Bernard MP, Timpl R (Oct 1987). "Characterization of three constituent chains of collagen type VI by peptide sequences and cDNA clones". European Journal of Biochemistry / FEBS 168 (2): 309–17. doi:10.1111/j.1432-1033.1987.tb13422.x. PMID 3665927. 
  • Arnoux B, Mérigeau K, Saludjian P, Norris F, Norris K, Bjørn S, Olsen O, Petersen L, Ducruix A (Mar 1995). "The 1.6 A structure of Kunitz-type domain from the alpha 3 chain of human type VI collagen". Journal of Molecular Biology 246 (5): 609–17. doi:10.1016/S0022-2836(05)80110-X. PMID 7533217. 
  • Pfaff M, Aumailley M, Specks U, Knolle J, Zerwes HG, Timpl R (May 1993). "Integrin and Arg-Gly-Asp dependence of cell adhesion to the native and unfolded triple helix of collagen type VI". Experimental Cell Research 206 (1): 167–76. doi:10.1006/excr.1993.1134. PMID 8387021. 
  • Jöbsis GJ, Keizers H, Vreijling JP, de Visser M, Speer MC, Wolterman RA, Baas F, Bolhuis PA (Sep 1996). "Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures". Nature Genetics 14 (1): 113–5. doi:10.1038/ng0996-113. PMID 8782832. 
  • Zweckstetter M, Czisch M, Mayer U, Chu ML, Zinth W, Timpl R, Holak TA (Feb 1996). "Structure and multiple conformations of the kunitz-type domain from human type VI collagen alpha3(VI) chain in solution". Structure 4 (2): 195–209. doi:10.1016/S0969-2126(96)00022-6. PMID 8805527. 
  • Myint E, Brown DJ, Ljubimov AV, Kyaw M, Kenney MC (Sep 1996). "Cleavage of human corneal type VI collagen alpha 3 chain by matrix metalloproteinase-2". Cornea 15 (5): 490–6. doi:10.1097/00003226-199609000-00009. PMID 8862926. 
  • Sorensen MD, Bjorn S, Norris K, Olsen O, Petersen L, James TL, Led JJ (Aug 1997). "Solution structure and backbone dynamics of the human alpha3-chain type VI collagen C-terminal Kunitz domain,". Biochemistry 36 (34): 10439–50. doi:10.1021/bi9705570. PMID 9265624. 
  • Lamandé SR, Sigalas E, Pan TC, Chu ML, Dziadek M, Timpl R, Bateman JF (Mar 1998). "The role of the alpha3(VI) chain in collagen VI assembly. Expression of an alpha3(VI) chain lacking N-terminal modules N10-N7 restores collagen VI assembly, secretion, and matrix deposition in an alpha3(VI)-deficient cell line". The Journal of Biological Chemistry 273 (13): 7423–30. doi:10.1074/jbc.273.13.7423. PMID 9516440. 
  • Klewer SE, Krob SL, Kolker SJ, Kitten GT (Mar 1998). "Expression of type VI collagen in the developing mouse heart". Developmental Dynamics 211 (3): 248–55. doi:10.1002/(SICI)1097-0177(199803)211:3<248::AID-AJA6>3.0.CO;2-H. PMID 9520112. 
  • Pan TC, Zhang RZ, Pericak-Vance MA, Tandan R, Fries T, Stajich JM, Viles K, Vance JM, Chu ML, Speer MC (May 1998). "Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy". Human Molecular Genetics 7 (5): 807–12. doi:10.1093/hmg/7.5.807. PMID 9536084. 
  • Aigner T, Hambach L, Söder S, Schlötzer-Schrehardt U, Pöschl E (Jan 2002). "The C5 domain of Col6A3 is cleaved off from the Col6 fibrils immediately after secretion". Biochemical and Biophysical Research Communications 290 (2): 743–8. doi:10.1006/bbrc.2001.6227. PMID 11785962. 
  • Mercuri E, Yuva Y, Brown SC, Brockington M, Kinali M, Jungbluth H, Feng L, Sewry CA, Muntoni F (May 2002). "Collagen VI involvement in Ullrich syndrome: a clinical, genetic, and immunohistochemical study". Neurology 58 (9): 1354–9. doi:10.1212/wnl.58.9.1354. PMID 12011280. 
  • Arnoux B, Ducruix A, Prangé T (Jul 2002). "Anisotropic behaviour of the C-terminal Kunitz-type domain of the alpha3 chain of human type VI collagen at atomic resolution (0.9 A)". Acta Crystallographica. Section D, Biological Crystallography 58 (Pt 7): 1252–4. doi:10.1107/S0907444902007333. PMID 12077460. 

External links[edit]