KDEL Receptor (KR_10) Mouse mAb
- Known as:
- KDEL Receptor (KR_10) Mouse mAb
- Catalog number:
- ASAVAA-PT048D
- Product Quantity:
- 50 µL
- Category:
- -
- Supplier:
- Other suppliers
- Gene target:
- KDEL Receptor (KR_10) Mouse mAb
Related genes to: KDEL Receptor (KR_10) Mouse mAb
- Gene:
- POGLUT1 NIH gene
- Name:
- protein O-glucosyltransferase 1
- Previous symbol:
- C3orf9, KTELC1
- Synonyms:
- MDS010, MGC32995, 9630046K23Rik, MDSRP, hCLP46, KDELCL1, Rumi
- Chromosome:
- 3q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2005-11-28
- Date modifiied:
- 2014-11-19
- Gene:
- POGLUT2 NIH gene
- Name:
- protein O-glucosyltransferase 2
- Previous symbol:
- KDELC1
- Synonyms:
- MGC5302, EP58
- Chromosome:
- 13q33.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-12-16
- Date modifiied:
- 2019-02-15
- Gene:
- POGLUT3 NIH gene
- Name:
- protein O-glucosyltransferase 3
- Previous symbol:
- KDELC2
- Synonyms:
- MGC33424
- Chromosome:
- 11q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-27
- Date modifiied:
- 2019-02-15
Related products to: KDEL Receptor (KR_10) Mouse mAb
Related articles to: KDEL Receptor (KR_10) Mouse mAb
- O-glycosylation of Notch epidermal growth factor-like (EGF) repeats has long been studied in the context of protein folding, secretion from cells, and protein function. Originally, the protein O-glucosyltransferase, POGLUT1, was thought to be the only enzyme adding an O-glucose modification to EGFs, specifically to a serine between cysteine one and two of a six cysteine containing EGF repeat. The POGLUT1 O-glucose can be elongated on Notch EGFs with xyloses by GXYLT1/2 and XXYLT1, forming a trisaccharide. Mouse knockouts of Poglut1 are embryonic lethal with Notch1-related phenotypes. Recently, protein O-glucosyltransferases POGLUT2 and POGLUT3 were shown to add an O-glucose modification to a serine located between cysteine three and four, distinct from the POGLUT1 modification. This modification was first discovered on EGF11 of NOTCH1, then subsequently mapped on extracellular matrix proteins fibrillin-1 (FBN1), fibrillin-2 (FBN2), and latent transforming growth factor beta-binding protein 1 (LTBP1). Poglut2/3 double knockout mice exhibit neonatal lethality like Fbn1 or Ltbp1 knockouts. In addition, Poglut2/3 double knockout mice display syndactyly, similar to Fbn2 knockouts. These studies also showed decreased secretion of FBN1 and 2 from fibroblasts and incorporation into the extracellular matrix. Site mapping established a putative POGLUT2/3 consensus sequence: C-x-N-T-x-G-S-F/Y-x-C. Alanine variants at conserved residues redefined consensus to: C-x-x-x-x-x-S-x-x-C. Marfan syndrome (MFS) is caused by FBN1 variants, and MFS variants in the POGLUT2/3 consensus display aberrant O-glucosylation. With the neonatal lethality of mouse Poglut2/3 double knockouts and the changes in O-glucosylation caused by MFS variants, further examination of the effects of O-glucose on FBN1 function are needed. - Source: PubMed
Publication date: 2026/04/08
Kegley Nicholas RHoldener Bernadette CHaltiwanger Robert S - O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). All of these modifications affect Notch activity. Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. Cellular assays showed that loss of modifications by POGLUT2 and/or POGLUT3 significantly reduces FBN1 secretion. There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. - Source: PubMed
Williamson Daniel BHaltiwanger Robert S - Fibrillin-1 (FBN1) is the major component of extracellular matrix microfibrils, which are required for proper development of elastic tissues, including the heart and lungs. Through protein-protein interactions with latent transforming growth factor (TGF) β-binding protein 1 (LTBP1), microfibrils regulate TGF-β signaling. Mutations within the 47 epidermal growth factor-like (EGF) repeats of FBN1 cause autosomal dominant disorders including Marfan Syndrome, which is characterized by disrupted TGF-β signaling. We recently identified two novel protein O-glucosyltransferases, Protein O-glucosyltransferase 2 (POGLUT2) and 3 (POGLUT3), that modify a small fraction of EGF repeats on Notch. Here, using mass spectral analysis, we show that POGLUT2 and POGLUT3 also modify over half of the EGF repeats on FBN1, fibrillin-2 (FBN2), and LTBP1. While most sites are modified by both enzymes, some sites show a preference for either POGLUT2 or POGLUT3. POGLUT2 and POGLUT3 are homologs of POGLUT1, which stabilizes Notch proteins by addition of O-glucose to Notch EGF repeats. Like POGLUT1, POGLUT2 and 3 can discern a folded versus unfolded EGF repeat, suggesting POGLUT2 and 3 are involved in a protein folding pathway. In vitro secretion assays using the N-terminal portion of recombinant FBN1 revealed reduced FBN1 secretion in POGLUT2 knockout, POGLUT3 knockout, and POGLUT2 and 3 double-knockout HEK293T cells compared with wild type. These results illustrate that POGLUT2 and 3 function together to O-glucosylate protein substrates and that these modifications play a role in the secretion of substrate proteins. It will be interesting to see how disease variants in these proteins affect their O-glucosylation. - Source: PubMed
Publication date: 2021/08/17
Williamson Daniel BSohn Camron JIto AtsukoHaltiwanger Robert S - The Notch-signaling pathway is normally activated by Notch-ligand interactions. A recent structural analysis suggested that a novel -linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands. This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein -glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible. Here, we identify two novel protein -glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer -glucose (-Glc) from UDP-Glc to serine 435. Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking , , or both genes showed that either POGLUT2 or POGLUT3 can add this novel -Glc modification. EGF11 of NOTCH2 does not have a serine residue in the same location for this -glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position. Comparison of the sites suggests a consensus sequence for modification. In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10. Mutation of the -Glc modification site on EGF11 (serine 435) in combination with sensitizing -fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively. This study identifies a previously undescribed mechanism for fine-tuning the Notch-signaling pathway in mammals. - Source: PubMed
Publication date: 2018/08/20
Takeuchi HideyukiSchneider MichaelWilliamson Daniel BIto AtsukoTakeuchi MegumiHandford Penny AHaltiwanger Robert S