Details for: XYLT2

Gene ID: 64132

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: XYLT2

Ensembl ID: ENSG00000015532

Description: xylosyltransferase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural progenitor cell CL0011020
    CSI 4.27
    rCSI 18.8%
    PRS 91.83
  • glial cell CL0000125
    CSI 3.4
    rCSI 12.96%
    PRS 94.83
  • mucous neck cell CL0000651
    CSI 2.85
    rCSI 4.1%
    PRS 98
  • GABAergic neuron CL0000617
    CSI 2.68
    rCSI 8.99%
    PRS 90.94
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.68
    rCSI 3.33%
    PRS 92.16
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.52
    rCSI 3.01%
    PRS 93.42
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.34
    rCSI 5.26%
    PRS 93.54
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.34
    rCSI 3.01%
    PRS 93.89
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.97
    rCSI 3.3%
    PRS 93.7
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.66
    rCSI 4.2%
    PRS 96.03
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.14
    rCSI 7.14%
    PRS 94.71
  • peptic cell CL0000155
    CSI 0.91
    rCSI 8.97%
    PRS 98.08
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.68
    rCSI 2.43%
    PRS 92.31

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Xylosyltransferase 2, encoded by the [XYLT2](/details-gene/64132) gene, is a key enzyme that initiates the biosynthesis of glycosaminoglycan (GAG) chains by catalyzing the transfer of UDP-xylose to serine residues on core proteins. This is the first and rate-limiting step in the formation of proteoglycans such as chondroitin sulfate and heparan sulfate ([Link](https://doi.org/10.1074/jbc.m611665200)). Functionally, it operates within the Golgi apparatus and is crucial for the proper synthesis of the extracellular matrix. **Overall**, expression data indicates that [XYLT2](/details-gene/64132) has its highest significance in the central nervous system, particularly in [neural progenitor cell](/details-cell/CL0011020), [glial cell](/details-cell/CL0000125), and various subtypes of [GABAergic neuron](/details-cell/CL0000617). Clinically, homozygous mutations in [XYLT2](/details-gene/64132) are known to cause spondylo-ocular syndrome, a rare genetic disorder characterized by bone fragility, cataracts, and hearing defects ([Link](https://doi.org/10.1016/j.ajhg.2015.04.017)). ## Cellular Roles and Expression Landscape The expression profile of [XYLT2](/details-gene/64132) points to a fundamental role in tissues with a high demand for proteoglycan synthesis, with a pronounced significance in the nervous system. **Overall**, the gene shows the highest significance in a variety of neural cell types. It is a top marker for [neural progenitor cell](/details-cell/CL0011020) (CSI: 4.27) and [glial cell](/details-cell/CL0000125) (CSI: 3.40), including more specialized subtypes like [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 2.34). This suggests a critical role in neurodevelopment and the maintenance of the neural extracellular matrix, which is vital for cell migration, axon guidance, and synaptic plasticity. Furthermore, its high significance in several cortical interneuron populations, such as [GABAergic neuron](/details-cell/CL0000617) (CSI: 2.68) and its [pvalb](/details-cell/CL4023018), [VIP](/details-cell/CL4023016), and [sst](/details-cell/CL4023017) subtypes, is consistent with the importance of the perineuronal net, a GAG-rich structure that envelops these neurons. Beyond the nervous system, [XYLT2](/details-gene/64132) also shows notable significance in secretory and specialized epithelial cells, including [mucous neck cell](/details-cell/CL0000651) (CSI: 2.85) and [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 1.66). This pattern suggests a conserved function in building the GAG components of the extracellular matrix or secreted proteoglycans in diverse tissues. ## Pathways and Molecular Function The functional annotations for [XYLT2](/details-gene/64132) align precisely with its role as a foundational enzyme in proteoglycan synthesis. Its molecular function is defined as protein xylosyltransferase activity ([GO:0030158](https://www.ebi.ac.uk/QuickGO/term/GO:0030158)), requiring manganese ([GO:0030145](https://www.ebi.ac.uk/QuickGO/term/GO:0030145)) or magnesium ([GO:0000287](https://www.ebi.ac.uk/QuickGO/term/GO:0000287)) ions as cofactors. The biological processes it participates in are central to glycosaminoglycan metabolism ([GO:0030203](https://www.ebi.ac.uk/QuickGO/term/GO:0030203)) and biosynthesis ([GO:0006024](https://www.ebi.ac.uk/QuickGO/term/GO:0006024)). Specifically, it is involved in the synthesis of chondroitin sulfate ([GO:0030206](https://www.ebi.ac.uk/QuickGO/term/GO:0030206)) and heparan sulfate ([GO:0015012](https://www.ebi.ac.uk/QuickGO/term/GO:0015012)) proteoglycans. These pathways are further detailed in Reactome, which places [XYLT2](/details-gene/64132) at the start of GAG synthesis, where it creates the tetrasaccharide linker sequence ([R-HSA-1971475](https://reactome.org/content/detail/R-HSA-1971475)) common to both chondroitin sulfate/dermatan sulfate ([R-HSA-1793185](https://reactome.org/content/detail/R-HSA-1793185)) and heparan sulfate/heparin ([R-HSA-1638091](https://reactome.org/content/detail/R-HSA-1638091)) metabolism. This function is localized to the Golgi membrane ([GO:0000139](https://www.ebi.ac.uk/QuickGO/term/GO:0000139)), where post-translational modification of proteoglycan core proteins occurs. ## Research Directions The high significance of [XYLT2](/details-gene/64132) in neural cells, coupled with its known role in extracellular matrix synthesis, opens several avenues for future research into neurodevelopment and neuropathology. **Proposed Hypotheses:** 1. Given its high significance in [neural progenitor cell](/details-cell/CL0011020), [XYLT2](/details-gene/64132) activity is essential for proper cortical lamination during brain development, where it modulates cell-matrix interactions required for radial neuronal migration. 2. In the adult brain, dysregulation of [XYLT2](/details-gene/64132) expression in [astrocyte of the cerebral cortex](/details-cell/CL0002605) following injury may be a key driver of glial scar formation by altering the composition and inhibitory nature of chondroitin sulfate proteoglycans. **Experimental Approach:** To test the first hypothesis regarding neurodevelopment, a compelling approach would involve using human pluripotent stem cell (hPSC)-derived brain organoids. One could generate an [XYLT2](/details-gene/64132) knockout hPSC line using CRISPR-Cas9. By comparing the development of organoids from the knockout line to isogenic controls, researchers could assess key neurodevelopmental processes. A combination of immunofluorescence staining for neuronal layer markers (e.g., TBR1, CTIP2, SATB2) and live-cell imaging of migrating neurons would reveal defects in cortical organization. Furthermore, single-cell RNA sequencing at different developmental time points could uncover the downstream transcriptional consequences of altered GAG synthesis on neuronal differentiation and maturation pathways. **Therapeutic Potential:** The therapeutic potential of targeting [XYLT2](/details-gene/64132) is context-dependent. For the monogenic spondylo-ocular syndrome caused by loss-of-function mutations, strategies such as enzyme replacement therapy or gene therapy could be considered to restore xylosyltransferase activity. Conversely, in conditions characterized by pathological extracellular matrix deposition, such as glial scarring after spinal cord or brain injury, transient and localized inhibition of [XYLT2](/details-gene/64132) might be beneficial. As an enzyme, it represents a druggable target. However, its fundamental role in multiple tissues suggests that systemic inhibition would likely cause significant side effects, necessitating the development of highly targeted delivery systems for any inhibitory therapeutic.

Genular Protein ID: 1737873178

Symbol: XYLT2_HUMAN

Name: Xylosyltransferase 2

UniProtKB Accession Codes:

Q9H1B5 Q6UY41 Q86V00

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CTD 1 ChEBI 13 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 11 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 3 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 2 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11099377

Title: Molecular cloning and expression of human UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase and its first isoform XT-II.

PubMed ID: 11099377

DOI: 10.1006/jmbi.2000.4261

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16571645

Title: 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.

PubMed ID: 16571645

DOI: 10.1136/jmg.2006.040972

PubMed ID: 17189265

Title: Human xylosyltransferase II is involved in the biosynthesis of the uniform tetrasaccharide linkage region in chondroitin sulfate and heparan sulfate proteoglycans.

PubMed ID: 17189265

DOI: 10.1074/jbc.m611665200

PubMed ID: 18023272

Title: Heterologous expression and biochemical characterization of soluble human xylosyltransferase II.

PubMed ID: 18023272

DOI: 10.1016/j.bbrc.2007.10.206

PubMed ID: 26027496

Title: Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular syndrome with bone fragility, cataracts, and hearing defects.

PubMed ID: 26027496

DOI: 10.1016/j.ajhg.2015.04.017

PubMed ID: 25748573

Title: Xylosyltransferase II is the predominant isoenzyme which is responsible for the steady-state level of xylosyltransferase activity in human serum.

PubMed ID: 25748573

DOI: 10.1016/j.bbrc.2015.02.129

Sequence Information:

  • Length: 865
  • Mass: 96767
  • Checksum: EF477B7C3C1B964B
  • Sequence:
    • MVASARVQKL VRRYKLAIAT ALAILLLQGL VVWSFSGLEE DEAGEKGRQR KPRPLDPGEG 
SKDTDSSAGR RGSTGRRHGR WRGRAESPGV PVAKVVRAVT SRQRASRRVP PAPPPEAPGR 
QNLSGAAAGE ALVGAAGFPP HGDTGSVEGA PQPTDNGFTP KCEIVGKDAL SALARASTKQ 
CQQEIANVVC LHQAGSLMPK AVPRHCQLTG KMSPGIQWDE SQAQQPMDGP PVRIAYMLVV 
HGRAIRQLKR LLKAVYHEQH FFYIHVDKRS DYLHREVVEL AQGYDNVRVT PWRMVTIWGG 
ASLLRMYLRS MRDLLEVPGW AWDFFINLSA TDYPTRTNEE LVAFLSKNRD KNFLKSHGRD 
NSRFIKKQGL DRLFHECDSH MWRLGERQIP AGIVVDGGSD WFVLTRSFVE YVVYTDDPLV 
AQLRQFYTYT LLPAESFFHT VLENSLACET LVDNNLRVTN WNRKLGCKCQ YKHIVDWCGC 
SPNDFKPQDF LRLQQVSRPT FFARKFESTV NQEVLEILDF HLYGSYPPGT PALKAYWENT 
YDAADGPSGL SDVMLTAYTA FARLSLHHAA TAAPPMGTPL CRFEPRGLPS SVHLYFYDDH 
FQGYLVTQAV QPSAQGPAET LEMWLMPQGS LKLLGRSDQA SRLQSLEVGT DWDPKERLFR 
NFGGLLGPLD EPVAVQRWAR GPNLTATVVW IDPTYVVATS YDITVDTETE VTQYKPPLSR 
PLRPGPWTVR LLQFWEPLGE TRFLVLPLTF NRKLPLRKDD ASWLHAGPPH NEYMEQSFQG 
LSSILNLPQP ELAEEAAQRH TQLTGPALEA WTDRELSSFW SVAGLCAIGP SPCPSLEPCR 
LTSWSSLSPD PKSELGPVKA DGRLR

Genular Protein ID: 1741339120

Symbol: B4DT06_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DT06

Database IDs:

ARBA 22 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChEBI 7 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 2 GO 6 GeneTree 1 HGNC 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 3 Proteomes 2 ProteomicsDB 2 RefSeq 1 Rhea 3 SAM 1 UCSC 1 UniPathway 2 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 676
  • Mass: 75513
  • Checksum: 797994FD32FB37FA
  • Sequence:
    • MVASARVQKL VRRYKLAIAT ALAILLLQGL VVWSFSGLEE DEAGEKGRQR KPRPLDPGEG 
SKDTDSSAGR RGSTGRRHGR WRGRAESPGV PVAKVVRAVT SRQRASRRVP PAPPPEAPGR 
QNLSGAAAGE ALVGAAGFPP HGDTGSVEGA PQPTDNGFTP KCEIVGKDAL SALARASTKQ 
CQQEIANVVC LHQAGSLMPK AVPRHCQLTG KMSPGIQWDE SQAQQPMDGP PVRIAYMLVV 
HGRAIRQLKR LLKAVYHEQH FFYIHVDKRS DYLHREVVEL AQGYDNVRVT PWRMVTIWGG 
ASLLRMYLRS MRDLLEVPGW AWDFFINLSA TDYPTRTNEE LVAFLSKNRD KNFLKSHGRD 
NSRFIKKQGL DRLFHECDSH MWRLGERQIP AGIVVDGGSD WFVLTRSFVE YVVYTDDPLV 
AQLRQFYTYT LLPAESFFHT VLENSLACET LVDNNLRVTN WNRKLGCKCQ YKHIVDWCGC 
SPNDFKPQDF LRLQQVSRPT FFARKFESTV NQEVLEILDF HLYGSYPPGT PALKAYWENT 
YDAADGPSGL SDVMLTAYTA FARLSLHHAA TAAPPMGTPL CRFEPRGLPS SVHLYFYDDH 
FQGYLVTQAV QPSAQGPAET LEMWLMPQGS LKLLGRSDQA SRLQSLENRG LSMLPRLVSN 
SWPQAVLPLQ PPKALG