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
Gene location (Human)
Chr.	Chromosome 16 (human)
End	17,470,960 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	117,272,803 bp
RNA expression pattern
	Top expressed in
	tibia; ; hair follicle; ; Region I of hippocampus proper; ; synovial joint; ; retinal pigment epithelium; ; entorhinal cortex; ; Brodmann area 23; ; orbitofrontal cortex; ; palpebral conjunctiva; ; superior frontal gyrus;
	Top expressed in
	subiculum; ; primary motor cortex; ; retinal pigment epithelium; ; ventromedial nucleus; ; cingulate gyrus; ; paraventricular nucleus of hypothalamus; ; mammillary body; ; lateral hypothalamus; ; medial vestibular nucleus; ; globus pallidus;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein xylosyltransferase activity ; transferase activity ; acetylglucosaminyltransferase activity ; glycosyltransferase activity ; metal ion binding ;
Cellular component	integral component of membrane ; extracellular region ; Golgi apparatus ; endoplasmic reticulum membrane ; endoplasmic reticulum ; membrane ; Golgi membrane ; Golgi cis cisterna ; extracellular space ;
Biological process	chondroitin sulfate biosynthetic process ; heparan sulfate proteoglycan biosynthetic process ; glycosaminoglycan biosynthetic process ; glycosaminoglycan metabolic process ; proteoglycan biosynthetic process ; ossification involved in bone maturation ; embryonic skeletal system development ; chondroitin sulfate proteoglycan biosynthetic process ;
	Sources:Amigo / QuickGO
Orthologs
	64131
	233781
	ENSG00000103489 ; ENSG00000285395
	ENSMUSG00000030657
	Q86Y38
	Q811B1
	NM_022166
	NM_175645
	NP_071449
	NP_783576
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 04, 2023

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

Baratela-Scott syndrome

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

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}}

Related Research Articles

Keratin 18 is a type I cytokeratin. It is, together with its filament partner keratin 8, perhaps the most commonly found products of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene.

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. In this form, HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB, and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.

Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene.

Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.

In enzymology, a protein xylosyltransferase is an enzyme that catalyzes the chemical reaction in which a beta-D-xylosyl residue is transferred from UDP-D-xylose to the sidechain oxygen atom of a serine residue in a protein.

<span class="mw-page-title-main">ADAMTS1</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 1 is an enzyme that in humans is encoded by the ADAMTS1 gene.

Proto-oncogene tyrosine-protein kinase FER is an enzyme that in humans is encoded by the FER gene.

Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the EIF2S2 gene.

Galactoside 2-alpha-L-fucosyltransferase 2 is an enzyme that in humans is encoded by the FUT2 gene. It affects the secretor status of ABO antigens.

Far upstream element-binding protein 2 is a protein that in humans is encoded by the KHSRP gene.

Lipid phosphate phosphohydrolase 1 also known as phosphatidic acid phosphatase 2a is an enzyme that in humans is encoded by the PPAP2A gene.

Aspartyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the DARS gene.

Beta-1,4-galactosyltransferase 7 also known as galactosyltransferase I is an enzyme that in humans is encoded by the B4GALT7 gene. Galactosyltransferase I catalyzes the synthesis of the glycosaminoglycan-protein linkage in proteoglycans. Proteoglycans in turn are structural components of the extracellular matrix that is found between cells in connective tissues.

Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 is an enzyme that in humans is encoded by the B3GAT3 gene.

Xylosyltransferase 2 is an enzyme that in humans is encoded by the XYLT2 gene.

Diacylglycerol kinase delta is an enzyme that in humans is encoded by the DGKD gene.

Mitochondrial tRNA-specific 2-thiouridylase 1 is an enzyme that in humans is encoded by the TRMU gene.

A disintegrin and metalloproteinase with thrombospondin motifs 9 is an enzyme that in humans is encoded by the ADAMTS9 gene.

<span class="mw-page-title-main">Xylosyltransferase</span> Class of enzymes

Xylosyltransferase are transferase enzymes which act upon xylose and are classified under EC 2.4.2.

Ribonuclease H1 also known as RNase H1 is an enzyme that in humans is encoded by the RNASEH1 gene. The RNase H1 is a non-specific endonuclease and catalyzes the cleavage of RNA via a hydrolytic mechanism.

References

1 2 3 ENSG00000285395 GRCh38: Ensembl release 89: ENSG00000103489, ENSG00000285395 - Ensembl, May 2017
1 2 3 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.
↑ Gotting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K (Jan 2001). "Molecular cloning and expression of human UDP-d-Xylose:proteoglycan core protein beta-d-xylosyltransferase and its first isoform XT-II". J Mol Biol. 304 (4): 517–28. doi:10.1006/jmbi.2000.4261. PMID 11099377.
1 2 "Entrez Gene: XYLT1 xylosyltransferase I".
↑ Baratela, Wagner A.R.; Bober, Michael B.; Tiller, George E.; Okenfuss, Ericka; Ditro, Colleen; Duker, Angela; Krakow, Deborah; Stabley, Deborah L.; Sol-Church, Katia; Mackenzie, William; Lachman, Ralph; Scott, Charles I. (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, Amy J.; Stabley, Deborah; Sahraoui, Rebecca; Adam, Margaret P.; Mehaffey, Michele; Kernan, Kelly; Myers, Candace T.; Fagerstrom, Carrie; Anadiotis, George; Akkari, Yassmine M.; Robbins, Katherine M.; Gripp, Karen W.; Baratela, Wagner A.R.; Bober, Michael B.; Duker, Angela L.; Doherty, Dan; Dempsey, Jennifer C.; Miller, Daniel G.; Kircher, Martin; Bamshad, Michael J.; Nickerson, Deborah A.; Mefford, Heather C.; Sol-Church, Katia (January 2019). "GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome". The American Journal of Human Genetics. 104 (1): 35–44. doi: 10.1016/j.ajhg.2018.11.005 . PMC 6323552 . PMID 30554721.

Götting C, Sollberg S, Kuhn J, et al. (1999). "Serum xylosyltransferase: a new biochemical marker of the sclerotic process in systemic sclerosis". J. Invest. Dermatol. 112 (6): 919–24. doi: 10.1046/j.1523-1747.1999.00590.x . PMID 10383739.
Kuhn J, Götting C, Schnölzer M, et al. (2001). "First isolation of human UDP-D-xylose: proteoglycan core protein beta-D-xylosyltransferase secreted from cultured JAR choriocarcinoma cells". J. Biol. Chem. 276 (7): 4940–7. doi: 10.1074/jbc.M005111200 . PMID 11087729.
Götting C, Kuhn J, Brinkmann T, Kleesiek K (2002). "Xylosyltransferase activity in seminal plasma of infertile men". Clin. Chim. Acta. 317 (1–2): 199–202. doi:10.1016/S0009-8981(01)00793-8. PMID 11814476.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC 139241 . PMID 12477932.
Götting C, Müller S, Schöttler M, et al. (2004). "Analysis of the DXD motifs in human xylosyltransferase I required for enzyme activity". J. Biol. Chem. 279 (41): 42566–73. doi: 10.1074/jbc.M401340200 . PMID 15294915.
Müller S, Schöttler M, Schön S, et al. (2005). "Human xylosyltransferase I: functional and biochemical characterization of cysteine residues required for enzymic activity". Biochem. J. 386 (Pt 2): 227–36. doi:10.1042/BJ20041206. PMC 1134786 . PMID 15461586.
Götting C, Hendig D, Adam A, et al. (2006). "Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis". J. Mol. Med. 83 (12): 984–92. doi:10.1007/s00109-005-0693-x. PMID 16133423. S2CID 9907867.
Schön S, Prante C, Müller S, et al. (2005). "Impact of polymorphisms in the genes encoding xylosyltransferase I and a homologue in type 1 diabetic patients with and without nephropathy". Kidney Int. 68 (4): 1483–90. doi: 10.1111/j.1523-1755.2005.00561.x . PMID 16164625.
Müller S, Disse J, Schöttler M, et al. (2006). "Human xylosyltransferase I and N-terminal truncated forms: functional characterization of the core enzyme". Biochem. J. 394 (Pt 1): 163–71. doi:10.1042/BJ20051606. PMC 1386014 . PMID 16225459.
Schön S, Prante C, Bahr C, et al. (2006). "Cloning and recombinant expression of active full-length xylosyltransferase I (XT-I) and characterization of subcellular localization of XT-I and XT-II". J. Biol. Chem. 281 (20): 14224–31. doi: 10.1074/jbc.M510690200 . PMID 16569644.
Schön S, Schulz V, Prante C, et al. (2007). "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". J. Med. Genet. 43 (9): 745–9. doi:10.1136/jmg.2006.040972. PMC 2593031 . PMID 16571645.
Prante C, Bieback K, Funke C, et al. (2006). "The formation of extracellular matrix during chondrogenic differentiation of mesenchymal stem cells correlates with increased levels of xylosyltransferase I." Stem Cells. 24 (10): 2252–61. doi: 10.1634/stemcells.2005-0508 . PMID 16778156. S2CID 40255873.
Schön S, Prante C, Bahr C, et al. (2007). "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): 2295–9. doi: 10.2337/dc06-0344 . PMID 17003309.
Cuellar K, Chuong H, Hubbell SM, Hinsdale ME (2007). "Biosynthesis of chondroitin and heparan sulfate in chinese hamster ovary cells depends on xylosyltransferase II". J. Biol. Chem. 282 (8): 5195–200. doi: 10.1074/jbc.M611048200 . PMID 17189266.
Prante C, Milting H, Kassner A, et al. (2007). "Transforming growth factor beta1-regulated xylosyltransferase I activity in human cardiac fibroblasts and its impact for myocardial remodeling". J. Biol. Chem. 282 (36): 26441–9. doi: 10.1074/jbc.M702299200 . PMID 17635914.
Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J (2005). "The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces". Molecular and Cellular Neuroscience. 28 (1): 18–29. doi:10.1016/j.mcn.2004.06.010. PMID 15607938. S2CID 38001196.
Hurtado A, Podini H, Oudega M, Grimpe B (2008). "Deoxyribozyme-mediated knock down of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord". Brain. 131 (10): 2596–605. doi:10.1093/brain/awn206. PMID 18765417.
Koenig B, Pape D, Chao O, Bauer J, Grimpe B (2016). "Long term study of deoxyribozyme administration to XT-1 mRNA promotes cortiospinal 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, Grimpe B (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.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 ENSG00000285395 GRCh38: Ensembl release 89: ENSG00000103489, ENSG00000285395 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030657 - 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.

[pmid11099377-5] Gotting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K (Jan 2001). "Molecular cloning and expression of human UDP-d-Xylose:proteoglycan core protein beta-d-xylosyltransferase and its first isoform XT-II". J Mol Biol. 304 (4): 517–28. doi:10.1006/jmbi.2000.4261. PMID 11099377.

[entrez-6] 1 2 "Entrez Gene: XYLT1 xylosyltransferase I".

[Baratela-Scott-7] Baratela, Wagner A.R.; Bober, Michael B.; Tiller, George E.; Okenfuss, Ericka; Ditro, Colleen; Duker, Angela; Krakow, Deborah; Stabley, Deborah L.; Sol-Church, Katia; Mackenzie, William; Lachman, Ralph; Scott, Charles I. (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.

[GCC_Repeat-8] LaCroix, Amy J.; Stabley, Deborah; Sahraoui, Rebecca; Adam, Margaret P.; Mehaffey, Michele; Kernan, Kelly; Myers, Candace T.; Fagerstrom, Carrie; Anadiotis, George; Akkari, Yassmine M.; Robbins, Katherine M.; Gripp, Karen W.; Baratela, Wagner A.R.; Bober, Michael B.; Duker, Angela L.; Doherty, Dan; Dempsey, Jennifer C.; Miller, Daniel G.; Kircher, Martin; Bamshad, Michael J.; Nickerson, Deborah A.; Mefford, Heather C.; Sol-Church, Katia (January 2019). "GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome". The American Journal of Human Genetics. 104 (1): 35–44. doi: 10.1016/j.ajhg.2018.11.005 . PMC 6323552 . PMID 30554721.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]