XYLT1
| XYLT1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | XYLT1, DBQD2, PXT-I, XT1, XTI, XYLTI, xylT-I, xylosyltransferase 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 608124; MGI: 2451073; HomoloGene: 32534; GeneCards: XYLT1; OMA:XYLT1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Xylosyltransferase 1 is an enzyme that in humans is encoded by the XYLT1 gene.[5][6]
Xylosyltransferase (XT; EC 2.4.2.26) catalyzes the transfer of UDP-xylose to serine residues within XT recognition sequences of target proteins. Addition of this xylose to the core protein is required for the biosynthesis of the glycosaminoglycan chains characteristic of proteoglycans.[supplied by OMIM][6]
Clinical relevance
[edit]Baratela-Scott syndrome
[edit]In 2012 Baratela-Scott syndrome was identified in humans.[7] A GGC repeat expansion, and methylation of exon 1 of XYLT1 is a common pathogenic variant in Baratela-Scott syndrome.[8]
Patients with Bartarlla-Scott syndrome exhibit abnormal development of the skeleton, characteristic facial features, and cognitive developmental delay. Skeletal problems include knee cap in the wrong position, short long bones with mild changes to the narrow portion, short palm bones with stub thumbs, short thigh necks, shallow hip sockets, and malformations of the spine. Characteristic facial features include a flattened midface with a broad nasal bridge, cleft palate, and unibrow. The syndrome also cause pre-school onset of a cognitive developmental delay, with a shortened attention span. Some of the cognitive delay is masked by a warm and engaging personality.
Axon extension
[edit]Neurons use the presence of extracellular matrix molecules as clues whether to promote or suppress extension of axons. Chondroitin sulfate proteoglycans suppress the extension of axons over the glial scar, a barrier which develops after lesioning the spinal cord. Proteoglycans consist of one relatively small protein core and attached large glycosaminoglycan side chains. To block the very formation of these side chains xylosyltransferase (XYLT1) which attaches xylose to a serine of the protein core as initiation for glycosaminoglycan chain extension, was targeted by a class of designed DNA molecules. These molecules are called DNA-enzymes which were designed to specifically cleave XYLT1 mRNA within cells. DNA-enzymes are readily taken up by mammalian cells, but are more stable and require much lower concentrations then siRNA. XTYL1 DNA-enzyme in co-cultures of neurons with neurocan secreting cells displayed a marked increase of axon outgrowth. Rats with defined spinal cord lesions, i.a. the clinically relevant contusion injury, treated with XTYL1 DNA-enzyme administered by micro-infusion pumps or systemically achieved improvements in the horizontal ladder task, enhanced axonal plasticity, growth of the corticospinal tract, no effect on neuropathic pain when using mechanical and thermal allodynia tests and no toxicological or pathological side effects compared to control animals.{{Oudega M, Chao OY, Avison DL, Bronson RT, Buchser WJ, Hurtado A, Grimpe B. (2012) Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord injury Exp Neurol. Sep;237(1):170-9. doi: 10.1016/j.expneurol.2012.06.006. PMID: 22721770}}
References
[edit]- ^ a b c ENSG00000285395 GRCh38: Ensembl release 89: ENSG00000103489, ENSG00000285395 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030657 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Götting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K (December 2000). "Molecular cloning and expression of human UDP-d-Xylose:proteoglycan core protein beta-d-xylosyltransferase and its first isoform XT-II". Journal of Molecular Biology. 304 (4): 517–528. doi:10.1006/jmbi.2000.4261. PMID 11099377.
- ^ a b "Entrez Gene: XYLT1 xylosyltransferase I".
- ^ Baratela WA, Bober MB, Tiller GE, Okenfuss E, Ditro C, Duker A, et al. (August 2012). "A newly recognized syndrome with characteristic facial features, skeletal dysplasia, and developmental delay". American Journal of Medical Genetics. Part A. 158A (8): 1815–1822. doi:10.1002/ajmg.a.35445. PMC 4164294. PMID 22711505.
- ^ LaCroix AJ, Stabley D, Sahraoui R, Adam MP, Mehaffey M, Kernan K, et al. (January 2019). "GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome". American Journal of Human Genetics. 104 (1): 35–44. doi:10.1016/j.ajhg.2018.11.005. PMC 6323552. PMID 30554721.
Further reading
[edit]- Götting C, Sollberg S, Kuhn J, Weilke C, Huerkamp C, Brinkmann T, et al. (June 1999). "Serum xylosyltransferase: a new biochemical marker of the sclerotic process in systemic sclerosis". The Journal of Investigative Dermatology. 112 (6): 919–924. doi:10.1046/j.1523-1747.1999.00590.x. PMID 10383739.
- Kuhn J, Götting C, Schnölzer M, Kempf T, Brinkmann T, Kleesiek K (February 2001). "First isolation of human UDP-D-xylose: proteoglycan core protein beta-D-xylosyltransferase secreted from cultured JAR choriocarcinoma cells". The Journal of Biological Chemistry. 276 (7): 4940–4947. doi:10.1074/jbc.M005111200. PMID 11087729.
- Götting C, Kuhn J, Brinkmann T, Kleesiek K (March 2002). "Xylosyltransferase activity in seminal plasma of infertile men". Clinica Chimica Acta; International Journal of Clinical Chemistry. 317 (1–2): 199–202. doi:10.1016/S0009-8981(01)00793-8. PMID 11814476.
- Götting C, Müller S, Schöttler M, Schön S, Prante C, Brinkmann T, et al. (October 2004). "Analysis of the DXD motifs in human xylosyltransferase I required for enzyme activity". The Journal of Biological Chemistry. 279 (41): 42566–42573. doi:10.1074/jbc.M401340200. PMID 15294915.
- Müller S, Schöttler M, Schön S, Prante C, Brinkmann T, Kuhn J, et al. (March 2005). "Human xylosyltransferase I: functional and biochemical characterization of cysteine residues required for enzymic activity". The Biochemical Journal. 386 (Pt 2): 227–236. doi:10.1042/BJ20041206. PMC 1134786. PMID 15461586.
- Götting C, Hendig D, Adam A, Schön S, Schulz V, Szliska C, et al. (December 2005). "Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis". Journal of Molecular Medicine. 83 (12): 984–992. doi:10.1007/s00109-005-0693-x. PMID 16133423. S2CID 9907867.
- Schön S, Prante C, Müller S, Schöttler M, Tarnow L, Kuhn J, et al. (October 2005). "Impact of polymorphisms in the genes encoding xylosyltransferase I and a homologue in type 1 diabetic patients with and without nephropathy". Kidney International. 68 (4): 1483–1490. doi:10.1111/j.1523-1755.2005.00561.x. PMID 16164625.
- Müller S, Disse J, Schöttler M, Schön S, Prante C, Brinkmann T, et al. (February 2006). "Human xylosyltransferase I and N-terminal truncated forms: functional characterization of the core enzyme". The Biochemical Journal. 394 (Pt 1): 163–171. doi:10.1042/BJ20051606. PMC 1386014. PMID 16225459.
- Schön S, Prante C, Bahr C, Kuhn J, Kleesiek K, Götting C (May 2006). "Cloning and recombinant expression of active full-length xylosyltransferase I (XT-I) and characterization of subcellular localization of XT-I and XT-II". The Journal of Biological Chemistry. 281 (20): 14224–14231. doi:10.1074/jbc.M510690200. PMID 16569644.
- Schön S, Schulz V, Prante C, Hendig D, Szliska C, Kuhn J, et al. (September 2006). "Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course". Journal of Medical Genetics. 43 (9): 745–749. doi:10.1136/jmg.2006.040972. PMC 2593031. PMID 16571645.
- Prante C, Bieback K, Funke C, Schön S, Kern S, Kuhn J, et al. (October 2006). "The formation of extracellular matrix during chondrogenic differentiation of mesenchymal stem cells correlates with increased levels of xylosyltransferase I". Stem Cells. 24 (10): 2252–2261. doi:10.1634/stemcells.2005-0508. PMID 16778156. S2CID 40255873.
- Schön S, Prante C, Bahr C, Tarnow L, Kuhn J, Kleesiek K, et al. (October 2006). "The xylosyltransferase I gene polymorphism c.343G>T (p.A125S) is a risk factor for diabetic nephropathy in type 1 diabetes". Diabetes Care. 29 (10): 2295–2299. doi:10.2337/dc06-0344. PMID 17003309.
- Cuellar K, Chuong H, Hubbell SM, Hinsdale ME (February 2007). "Biosynthesis of chondroitin and heparan sulfate in chinese hamster ovary cells depends on xylosyltransferase II". The Journal of Biological Chemistry. 282 (8): 5195–5200. doi:10.1074/jbc.M611048200. PMID 17189266.
- Prante C, Milting H, Kassner A, Farr M, Ambrosius M, Schön S, et al. (September 2007). "Transforming growth factor beta1-regulated xylosyltransferase I activity in human cardiac fibroblasts and its impact for myocardial remodeling". The Journal of Biological Chemistry. 282 (36): 26441–26449. doi:10.1074/jbc.M702299200. PMID 17635914.
- Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J (January 2005). "The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces". Molecular and Cellular Neurosciences. 28 (1): 18–29. doi:10.1016/j.mcn.2004.06.010. PMID 15607938. S2CID 38001196.
- Hurtado A, Podinin H, Oudega M, Grimpe B (October 2008). "Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord". Brain. 131 (Pt 10): 2596–2605. doi:10.1093/brain/awn206. PMID 18765417.
- Koenig B, Pape D, Chao O, Bauer J, Grimpe B (February 2016). "Long term study of deoxyribozyme administration to XT-1 mRNA promotes corticospinal tract regeneration and improves behavioral outcome after spinal cord injury". Experimental Neurology. 276: 51–58. doi:10.1016/j.expneurol.2015.09.015. PMID 26428904. S2CID 10575072.
- Oudega M, Chao OY, Avison DL, Bronson RT, Buchser WJ, Hurtado A, et al. (September 2012). "Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury". Experimental Neurology. 237 (1): 170–179. doi:10.1016/j.expneurol.2012.06.006. PMID 22721770. S2CID 34942901.