DPH2 Antibody (N-term) Blocking Peptide
- Known as:
- DPH2 Antibody (N-terminus) Blocking Peptide
- Catalog number:
- BP18264a
- Product Quantity:
- 2
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- DPH2 Antibody (N-term) Blocking Peptide
Related genes to: DPH2 Antibody (N-term) Blocking Peptide
- Gene:
- DPH1 NIH gene
- Name:
- diphthamide biosynthesis 1
- Previous symbol:
- DPH2L, DPH2L1
- Synonyms:
- OVCA1
- Chromosome:
- 17p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-08-25
- Date modifiied:
- 2015-08-25
- Gene:
- DPH2 NIH gene
- Name:
- diphthamide biosynthesis 2
- Previous symbol:
- DPH2L2
- Synonyms:
- -
- Chromosome:
- 1p34.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-24
- Date modifiied:
- 2019-02-14
Related products to: DPH2 Antibody (N-term) Blocking Peptide
Related articles to: DPH2 Antibody (N-term) Blocking Peptide
- Neurodevelopmental disorders (NDDs) represent a clinically diverse group of conditions that affect brain development, often leading to varying degrees of functional impairment. Many NDDs, particularly syndromic forms, are caused by genetic mutations affecting critical cellular pathways. Ribosomopathies, a subgroup of NDDs, are linked to defects in ribosomal function, including those involving the synthesis of diphthamide, a post-translational modification of translation elongation factor 2 (eEF2). Loss-of-function (LoF) mutations in genes involved in diphthamide biosynthesis, such as , , and , result in developmental delay (DD), intellectual disability (ID), and multisystemic abnormalities. DPH5-related diphthamide deficiency syndrome has recently been reported as an ultrarare disorder linked to LoF mutations in , encoding a methyltransferase required for diphthamide synthesis. - Source: PubMed
Publication date: 2025/07/02
Politano DavideMancini CeciliaCelario MassimilianoRadio Francesca ClementinaD'Abrusco FulvioGarau JessicaKalantari SilviaVisani GaiaCarbonera SimoneGana SimoneFerilli MarcoChiriatti LuigiCappelletti CamillaEllena KatiaProdi ElenaBorgatti RenatoValente Enza MariaOrcesi SimonaTartaglia MarcoSirchia Fabio - Diphthamide is a posttranslationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR 2 (eEF2) and the target of diphtheria toxin in human cells. In yeast and mammals, the 4Fe-4S cluster-containing proteins Dph1 and Dph2 catalyze the first biosynthetic step of diphthamide formation. Here, we identify Arabidopsis (Arabidopsis thaliana) DPH2 and show that it is required for diphthamide biosynthesis, localizes to the cytosol, and interacts physically with AtDPH1. Arabidopsis dph2 mutants form shorter primary roots and smaller rosettes than the wild type, similar to dph1 mutants which we characterized previously. Additionally, increased ribosomal -1 frameshifting error rates and attenuated TARGET OF RAPAMYCIN (TOR) kinase activity in dph2 mutants also phenocopy the dph1 mutant. Beyond the known heavy metal hypersensitivity and heat shock tolerance of dph1, we show here that both dph1 and dph2 mutants are hypersensitive to elevated light intensities and oxidative stress and that wild-type Arabidopsis seedlings accumulate diphthamide-unmodified eEF2 under oxidative stress. Both mutants share the deregulation of 1,186 transcripts associated with several environmental and hormone responses. AtDPH1 and AtDPH2 do not complement the corresponding mutants of Saccharomyces cerevisiae. In summary, DPH2 and DPH1 interact to function inter-dependently in diphthamide formation, the maintenance of translational fidelity, wild-type growth rates, and TOR kinase activation, and they contribute to mitigating damage from elevated light intensities and oxidative stress. Under oxidative stress, a dose-dependent loss of diphthamide could potentiate downstream effects in a feed-forward loop. This work advances our understanding of translation and its interactions with growth regulation and stress responses in plants. - Source: PubMed
Zhang HongliangJanina NadeždaÜtkür KorayManivannan ThirishikaZhang LeiWang LizhenGrefen ChristopherSchaffrath RaffaelKrämer Ute - The diphthamide () gene family is a group of genes that encode a set of enzymes that specifically modify eukaryotic elongation factor 2 (eEF2). Although previous studies have shown a link between the genes () and carcinogenesis, it is still unknown how the affect hepatocellular carcinoma (HCC). This study aimed to describe the expression, clinical significance, and potential mechanisms of in HCC. - Source: PubMed
Publication date: 2024/08/26
Gao XiaojinHe KunZeng ZhongxiangYin YaolinHuang JieLiu XingliangXiang XiaocongLi Jingdong - The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif is found next to another ill-defined cysteine that we show is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCMs) suggests a candidate Fe-S cluster ligand role. Hence, we generated, by site-directed and mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo. - Source: PubMed
Publication date: 2024/04/11
Ütkür KorayMayer KlausLiu ShihuiBrinkmann UlrichSchaffrath Raffael - In eukaryotes, the Dph1•Dph2 dimer is a non-canonical radical SAM enzyme. Using iron-sulfur (FeS) clusters, it cleaves the cosubstrate S-adenosyl-methionine (SAM) to form a 3-amino-3-carboxy-propyl (ACP) radical for the synthesis of diphthamide. The latter decorates a histidine residue on elongation factor 2 (EF2) conserved from archaea to yeast and humans and is important for accurate mRNA translation and protein synthesis. Guided by evidence from archaeal orthologues, we searched for a putative SAM-binding pocket in Dph1•Dph2 from . We predict an SAM-binding pocket near the FeS cluster domain that is conserved across eukaryotes in Dph1 but not Dph2. Site-directed mutagenesis and functional characterization through assay diagnostics for the loss of diphthamide reveal that the SAM pocket is essential for synthesis of the décor on EF2 in vivo. Further evidence from structural modeling suggests particularly critical residues close to the methionine moiety of SAM. Presumably, they facilitate a geometry specific for SAM cleavage and ACP radical formation that distinguishes Dph1•Dph2 from classical radical SAM enzymes, which generate canonical 5'-deoxyadenosyl (dAdo) radicals. - Source: PubMed
Publication date: 2023/11/16
Ütkür KoraySchmidt SarinaMayer KlausKlassen RolandBrinkmann UlrichSchaffrath Raffael