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]
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 abnormaldevelopment 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, shortpalm 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 extensionedit
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}}
^ abcGRCm38: 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.
^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. PMC4164294. 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. PMC6323552. PMID 30554721.
Further readingedit
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. PMC139241. 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. PMC1134786. 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. PMC1386014. 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. PMC2593031. 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.
January 01, 1970
xylt1, xylosyltransferase, enzyme, that, humans, encoded, gene, identifiersaliases, dbqd2, xylti, xylt, xylosyltransferase, 1external, idsomim, 608124, 2451073, homologene, 32534, genecards, gene, location, human, chromosome, human, band16p12, 3start17, end17,. Xylosyltransferase 1 is an enzyme that in humans is encoded by the XYLT1 gene 5 6 XYLT1IdentifiersAliasesXYLT1 DBQD2 PXT I XT1 XTI XYLTI xylT I xylosyltransferase 1External IDsOMIM 608124 MGI 2451073 HomoloGene 32534 GeneCards XYLT1Gene location Human Chr Chromosome 16 human 1 Band16p12 3Start17 101 769 bp 1 End17 470 960 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 7 F1Start116 980 214 bp 2 End117 272 803 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed intibiahair follicleRegion I of hippocampus propersynovial jointretinal pigment epitheliumentorhinal cortexBrodmann area 23orbitofrontal cortexpalpebral conjunctivasuperior frontal gyrusTop expressed insubiculumprimary motor cortexretinal pigment epitheliumventromedial nucleuscingulate gyrusparaventricular nucleus of hypothalamusmammillary bodylateral hypothalamusmedial vestibular nucleusglobus pallidusMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein xylosyltransferase activity transferase activity acetylglucosaminyltransferase activity glycosyltransferase activity metal ion bindingCellular componentintegral component of membrane extracellular region Golgi apparatus endoplasmic reticulum membrane endoplasmic reticulum membrane Golgi membrane Golgi cis cisterna extracellular spaceBiological processchondroitin 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 processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez64131233781EnsemblENSG00000103489ENSG00000285395ENSMUSG00000030657UniProtQ86Y38Q811B1RefSeq mRNA NM 022166NM 175645RefSeq protein NP 071449NP 783576Location UCSC Chr 16 17 1 17 47 MbChr 7 116 98 117 27 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse 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 Contents 1 Clinical relevance 1 1 Baratela Scott syndrome 1 2 Axon extension 2 References 3 Further readingClinical relevance editBaratela 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 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 a b 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 Further reading editGotting 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 Gotting C Schnolzer 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 Gotting 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 Gotting C Muller S Schottler 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 Muller S Schottler M Schon 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 Gotting 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 Schon S Prante C Muller 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 Muller S Disse J Schottler 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 Schon 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 Schon 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 Schon S Prante C Bahr C et al 2007 The xylosyltransferase I gene polymorphism c 343G gt 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 Retrieved from https en wikipedia org w index php title XYLT1 amp oldid 1188131474, wikipedia, wiki, book, books, library,
