CHST14

CHST14
Identifiers
Aliases	CHST14 , ATCS, D4ST1, EDSMC1, HNK1ST, carbohydrate sulfotransferase 14
External IDs	OMIM: 608429; MGI: 1919386; HomoloGene: 12443; GeneCards: CHST14; OMA:CHST14 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q15.1 Start 40,470,984 bp [1] End 40,473,158 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 E5 Start 118,756,977 bp [2] End 118,759,066 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium ventricular zone mucosa of ileum tibialis anterior muscle right ovary ascending aorta canal of the cervix placenta pancreatic ductal cell body of uterus Top expressed in lumbar spinal ganglion calvaria stroma of bone marrow endothelial cell of lymphatic vessel ascending aorta interventricular septum dermis semi-lunar valve renal corpuscle aortic valve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphate ion binding transferase activity sulfotransferase activity N-acetylgalactosamine 4-O-sulfotransferase activity Cellular component integral component of membrane Golgi membrane Golgi apparatus extracellular exosome membrane Biological process dermatan sulfate biosynthetic process carbohydrate biosynthetic process dermatan sulfate proteoglycan metabolic process carbohydrate metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 113189 72136 Ensembl ENSG00000169105 ENSMUSG00000074916 UniProt Q8NCH0 Q80V53 RefSeq (mRNA) NM_130468 NM_028117 RefSeq (protein) NP_569735 NP_082393 Location (UCSC) Chr 15: 40.47 – 40.47 Mb Chr 2: 118.76 – 118.76 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Carbohydrate sulfotransferase 14 is an enzyme that in humans is encoded by the CHST14 gene. ^{[5] [6]}

Gene

CHST14, a protein-coding gene, encodes for the enzyme carbohydrate sulfotransferase 14 (CHST14)/ dermatan 4-O-sulfotransferase (D4ST1). ^[5]

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. ^[5]

Ontology

CHST14 is implicated in fetal development of connective tissues throughout multiple organ systems. ^[7] It is also implicated in regulation of proliferation and neurogenesis of neural precursor cells. ^[8] It has been linked to inhibition of peripheral nerve regeneration in adults. ^[9]

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. ^[10] Dermatan sulfate is essential to extracellular matrix formation and is found in extensively in skin, tendons, cartilage, and the aortic wall. ^[11] Mutation of CHST14 results in a deficiency of dermatan sulfate, which disrupts glycosaminoglycan constituents in fibroblasts and impairs collagen fibril linkage within collagen bundles. ^[10]

Clinical significance

Mutation of CHST14 is associated with the Musculocontractural type of Ehlers–Danlos syndromes, recently specified as CHST14/D4ST1 deficiency. ^[7] Previously, this condition has been independently referred to as adducted thumb-clubfoot syndrome, ^[12] Ehlers-Danlos syndrome, Kosho type, ^{[10] [13]} musculocontractural Ehlers-Danlos syndrome, ^[14] and Ehlers-Danlos type VIB. ^[15] Currently, 40 patients from 27 families have been diagnosed with this autosomal recessive mutation. ^[16] CHST14/D4ST1 deficiency is the first identified human disease that directly impacts dermatan sulfate production. ^[16] " 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. ^[7]

References

1. GRCh38: Ensembl release 89: ENSG00000169105 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000074916 – 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. 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.
6. "Entrez Gene: D4ST1 dermatan 4 sulfotransferase 1".
7. 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. S2CID   5289682.
8. 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.
9. 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. S2CID   8093221.
10. 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. S2CID   46388905.
11. 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. doi: 10.1074/jbc.273.43.28116 . PMID   9774430.
12. 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   2790573 . PMID   20004762.
13. 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. S2CID   205312940.
14. 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. S2CID   39702597.
15. 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. S2CID   37675709.
16. 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. 50 (12): 670–677. doi:10.1016/j.clinbiochem.2017.02.018. hdl: 2115/68359 . PMID   28238810.

External links

• Human CHST14 genome location and CHST14 gene details page in the UCSC Genome Browser .

Further reading

• 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.