CHST14

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CHST14
Identifiers
Aliases CHST14, ATCS, D4ST1, EDSMC1, HNK1ST, carbohydrate sulfotransferase 14
External IDs MGI: 1919386 HomoloGene: 12443 GeneCards: CHST14
RNA expression pattern
PBB GE D4ST1 gnf1h09239 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_130468

NM_028117

RefSeq (protein)

NP_569735

NP_082393.3
NP_082393

Location (UCSC) Chr 15: 40.47 – 40.47 Mb Chr 2: 118.93 – 118.93 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Carbohydrate sulfotransferase 14 is an enzyme that in humans is encoded by the CHST14 gene.[3][4]

Gene[edit]

CHST14, a protein-coding gene, encodes for the enzyme carbohydrate sulfotransferase 14 (CHST14)/ dermatan 4-O-sulfotransferase (D4ST1).[3]

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.[3]

Ontology[edit]

CHST14 is implicated in fetal development of connective tissues throughout multiple organ systems.[5] It is also implicated in regulation of proliferation and neurogenesis of neural precursor cells.[6] CHST14 has been linked to inhibition of peripheral nerve regeneration in adults.[7]

Function[edit]

Dermatan 4-O-sulfotransferase enzymatically transfers an active sulfate to position 4 of N-acetyl-D-galactosamine residues of dermatan sulfate, stabilizing this glycosaminoglycan.[8] Dermatan sulfate is essential to extracellular matrix formation and is found in extensively in skin, tendons, cartilage, and the aortic wall.[9] Mutation of CHST14 results in a deficiency of dermatan sulfate, which disrupts glycosaminoglycan constituents in fibroblasts and impairs collagen fibril linkage within collagen bundles.[8]

Clinical significance[edit]

Mutation of CHST14 is associated with a specific type of Ehlers-Danlos syndrome, recently specified as CHST14/D4ST1 deficiency.[5] Previously, this condition has been independently referred to as adducted thumb-clubfoot syndrome,[10] Ehlers-Danlos syndrome, Kosho type,[8][11] musculocontractural Ehlers-Danlos syndrome,[12] and Ehlers-Danlos type VIB.[13] Currently, 40 patients from 27 families have been diagnosed with this autosomal recessive mutation.[14] CHST14/D4ST1 deficiency is the first identified human disease that directly impacts dermatan sulfate production.[14]" 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 diverticular perforation.[5]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ a b c Evers MR, Xia G, Kang HG, Schachner M, Baenziger JU (September 2001). "Molecular cloning and characterization of a dermatan-specific N-acetylgalactosamine 4-O-sulfotransferase". The Journal of Biological Chemistry. 276 (39): 36344–53. doi:10.1074/jbc.M105848200. PMID 11470797. 
  4. ^ "Entrez Gene: D4ST1 dermatan 4 sulfotransferase 1". 
  5. ^ a b c Kosho T (February 2016). "CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome". Pediatrics International. 58 (2): 88–99. doi:10.1111/ped.12878. PMID 26646600. 
  6. ^ Bian S, Akyüz N, Bernreuther C, Loers G, Laczynska E, Jakovcevski I, Schachner M (December 2011). "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. doi:10.1242/jcs.088120. PMID 22159417. 
  7. ^ Akyüz N, Rost S, Mehanna A, Bian S, Loers G, Oezen I, Mishra B, Hoffmann K, Guseva D, Laczynska E, Irintchev A, Jakovcevski I, Schachner M (September 2013). "Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration". Experimental Neurology. 247: 517–30. doi:10.1016/j.expneurol.2013.01.025. PMID 23360803. 
  8. ^ a b c Miyake N, Kosho T, Mizumoto S, Furuichi T, Hatamochi A, Nagashima Y, et al. (August 2010). "Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome". Human Mutation. 31 (8): 966–74. doi:10.1002/humu.21300. PMID 20533528. 
  9. ^ Penc SF, Pomahac B, Winkler T, Dorschner RA, Eriksson E, Herndon M, Gallo RL (October 1998). "Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function". The Journal of Biological Chemistry. 273 (43): 28116–21. PMID 9774430. 
  10. ^ Dündar M, Müller T, Zhang Q, Pan J, Steinmann B, Vodopiutz J, Gruber R, Sonoda T, Krabichler B, Utermann G, Baenziger JU, Zhang L, Janecke AR (December 2009). "Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome". American Journal of Human Genetics. 85 (6): 873–82. doi:10.1016/j.ajhg.2009.11.010. PMC 2790573Freely accessible. PMID 20004762. 
  11. ^ Kosho T, Miyake N, Hatamochi A, Takahashi J, Kato H, Miyahara T, et al. (June 2010). "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. doi:10.1002/ajmg.a.33498. PMID 20503305. 
  12. ^ Malfait F, Syx D, Vlummens P, Symoens S, Nampoothiri S, Hermanns-Lê T, Van Laer L, De Paepe A (November 2010). "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. doi:10.1002/humu.21355. PMID 20842734. 
  13. ^ Kosho T, Takahashi J, Ohashi H, Nishimura G, Kato H, Fukushima Y (October 2005). "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. doi:10.1002/ajmg.a.30965. PMID 16158441. 
  14. ^ a b Mizumoto S, Kosho T, Hatamochi A, Honda T, Yamaguchi T, Okamoto N, Miyake N, Yamada S, Sugahara K (February 2017). "Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency". Clinical Biochemistry. doi:10.1016/j.clinbiochem.2017.02.018. PMID 28238810. 

External links[edit]

Further reading[edit]

  • Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "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. doi:10.1093/dnares/12.2.117. PMID 16303743. 
  • Mikami T, Mizumoto S, Kago N, Kitagawa H, Sugahara K (September 2003). "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. doi:10.1074/jbc.M306044200. PMID 12847091.