Biology:CHST14

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Generic protein structure example

Carbohydrate sulfotransferase 14 is an enzyme that in humans is encoded by the CHST14 gene.[1][2]

Gene

CHST14, a protein-coding gene, encodes for the enzyme carbohydrate sulfotransferase 14 (CHST14)/ dermatan 4-O-sulfotransferase (D4ST1).[1]

In humans, CHST14 is positioned on the long arm (q) of chromosome 15 at position 15.1, from base pair 40,470,961 to base pair 40,474,571. The CHST14 gene is 3,611 bases long, composed of 376 amino acids, and has a molecular mass of 42997 Da.[1]

Ontology

CHST14 is implicated in fetal development of connective tissues throughout multiple organ systems.[3] It is also implicated in regulation of proliferation and neurogenesis of neural precursor cells.[4] It has been linked to inhibition of peripheral nerve regeneration in adults.[5]

Function

Dermatan 4-O-sulfotransferase enzymatically transfers an active sulfate to position 4 of N-acetyl-D-galactosamine residues of dermatan sulfate, stabilizing this glycosaminoglycan.[6] Dermatan sulfate is essential to extracellular matrix formation and is found in extensively in skin, tendons, cartilage, and the aortic wall.[7] Mutation of CHST14 results in a deficiency of dermatan sulfate, which disrupts glycosaminoglycan constituents in fibroblasts and impairs collagen fibril linkage within collagen bundles.[6]

Clinical significance

Mutation of CHST14 is associated with the Musculocontractural type of Ehlers–Danlos syndromes, recently specified as CHST14/D4ST1 deficiency.[3] Previously, this condition has been independently referred to as adducted thumb-clubfoot syndrome,[8] Ehlers-Danlos syndrome, Kosho type,[6][9] musculocontractural Ehlers-Danlos syndrome,[10] and Ehlers-Danlos type VIB.[11] Currently, 40 patients from 27 families have been diagnosed with this autosomal recessive mutation.[12] CHST14/D4ST1 deficiency is the first identified human disease that directly impacts dermatan sulfate production.[12]" Hallmark features include congenital malformations (extensive craniofacial defects, skin elasticity, joint laxity, multiple contractures) combined with progressive fragility of affected structures, with increased incidence of bruising, recurrent joint dislocations, pneumothorax, spinal degeneration, and other deformities.[3]

References

  1. ↑ 1.0 1.1 1.2 "Molecular cloning and characterization of a dermatan-specific N-acetylgalactosamine 4-O-sulfotransferase". The Journal of Biological Chemistry 276 (39): 36344–53. September 2001. doi:10.1074/jbc.M105848200. PMID 11470797. 
  2. ↑ "Entrez Gene: D4ST1 dermatan 4 sulfotransferase 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=113189. 
  3. ↑ 3.0 3.1 3.2 "CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome". Pediatrics International 58 (2): 88–99. February 2016. doi:10.1111/ped.12878. PMID 26646600. 
  4. ↑ "Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells". Journal of Cell Science 124 (Pt 23): 4051–63. December 2011. doi:10.1242/jcs.088120. PMID 22159417. 
  5. ↑ "Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration". Experimental Neurology 247: 517–30. September 2013. doi:10.1016/j.expneurol.2013.01.025. PMID 23360803. 
  6. ↑ 6.0 6.1 6.2 "Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome". Human Mutation 31 (8): 966–74. August 2010. doi:10.1002/humu.21300. PMID 20533528. 
  7. ↑ "Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function". The Journal of Biological Chemistry 273 (43): 28116–21. October 1998. doi:10.1074/jbc.273.43.28116. PMID 9774430. 
  8. ↑ "Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome". American Journal of Human Genetics 85 (6): 873–82. December 2009. doi:10.1016/j.ajhg.2009.11.010. PMID 20004762. 
  9. ↑ "A new Ehlers-Danlos syndrome with craniofacial characteristics, multiple congenital contractures, progressive joint and skin laxity, and multisystem fragility-related manifestations". American Journal of Medical Genetics. Part A 152A (6): 1333–46. June 2010. doi:10.1002/ajmg.a.33498. PMID 20503305. 
  10. ↑ "Musculocontractural Ehlers-Danlos Syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene". Human Mutation 31 (11): 1233–9. November 2010. doi:10.1002/humu.21355. PMID 20842734. https://hal.archives-ouvertes.fr/hal-00599478/document. 
  11. ↑ "Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls". American Journal of Medical Genetics. Part A 138A (3): 282–7. October 2005. doi:10.1002/ajmg.a.30965. PMID 16158441. 
  12. ↑ 12.0 12.1 "Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency". Clinical Biochemistry 50 (12): 670–677. February 2017. doi:10.1016/j.clinbiochem.2017.02.018. PMID 28238810. 

External links

Further reading

  • "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research 12 (2): 117–26. 2007. doi:10.1093/dnares/12.2.117. PMID 16303743. 
  • "Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor: implication of differential roles in dermatan sulfate biosynthesis". The Journal of Biological Chemistry 278 (38): 36115–27. September 2003. doi:10.1074/jbc.M306044200. PMID 12847091. 





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