Ask about this productRelated genes to: FICD antibody
- Gene:
- FICD NIH gene
- Name:
- FIC domain containing
- Previous symbol:
- -
- Synonyms:
- HYPE, HIP13
- Chromosome:
- 12q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 2007-12-04
- Date modifiied:
- 2016-10-05
Related products to: FICD antibody
Related articles to: FICD antibody
- Filamentation induced by cAMP domain-containing protein (FICD) is an endoplasmic reticulum (ER)-resident adenylyltransferase that catalyzes protein AMPylation, a post-translational modification. Although FICD-mediated AMPylation has been linked to the fine-tuning of proteostasis and neuronal integrity, its role in neurodegenerative diseases characterized by protein dyshomeostasis remains unclear. Parkinson's disease (PD) is defined by dopaminergic neurodegeneration and aggregation of α-synuclein (aSyn) as a consequence of impaired protein homeostasis. We therefore investigated whether dysregulated FICD-mediated AMPylation contributes to PD pathogenesis. - Source: PubMed
Publication date: 2026/04/01
Koller AronHoffmann LauraBluhm AlexandraSchweigert AlinaSchneider YanniAndert MarieBecker TobiasZunke FriederikeBeach Thomas GSerrano Geidy ERoßner SteffenWinkler JürgenKielkowski PavelXiang Wei - Magnetic resonance imaging (MRI) and positron emission tomography (PET) are increasingly used in multimodal analysis of neurodegenerative disorders. While MRI is broadly utilized in clinical settings, PET is less accessible. Many studies have attempted to use deep generative models to synthesize PET from MRI scans. However, they often suffer from unstable training and inadequately preserve brain functional information conveyed by PET. To this end, we propose a functional imaging constrained diffusion (FICD) framework for 3D brain PET image synthesis with paired structural MRI as input condition, through a new constrained diffusion model (CDM). The FICD introduces noise to PET and then progressively removes it with CDM, ensuring high output fidelity throughout a stable training phase. The CDM learns to predict denoised PET with a functional imaging constraint introduced to ensure voxel-wise alignment between each denoised PET and its ground truth. Quantitative and qualitative analyses conducted on 293 subjects with paired T1-weighted MRI and F-fluorodeoxyglucose (FDG)-PET scans suggest that FICD achieves superior performance in generating FDG-PET data compared to state-of-the-art methods. We further validate the effectiveness of the proposed FICD on data from a total of 1262 subjects through three downstream tasks, with experimental results suggesting its utility and generalizability. - Source: PubMed
Publication date: 2026/03/27
Yu MinhuiWu MengqiYue LingBozoki AndreaLiu Mingxia - FicD regulates Unfolded Protein Response (UPR) through reversible AMPylation and deAMPylation of BiP, an HSP70 chaperone and master regulator of the UPR. FicD activity is regulated by endoplasmic reticulum-stress, catalyzing BiP AMPylation under low stress conditions to hold inactive chaperone in reserve. In stressed cells, FicD deAMPylates BiP, acutely increasing its active pool to assist in protein folding. Variants in UPR machinery, including those in the gene, are linked to hereditary diseases. Despite the known role of FicD in UPR, in-vivo regulation of its activity remains elusive, and identifying metabolites that alter FicD activity could prove useful pharmaceutically. We applied an unbiased high-throughput screening platform, known as Mass spectrometry Integrated with equilibrium Dialysis for the discovery of Allostery Systematically (MIDAS), to identify small molecule metabolites that might regulate FicD activity. MIDAS revealed interactions between FicD and two mevalonate pathway intermediates: geranyl-pyrophosphate and farnesyl-pyrophosphate. Biochemical characterization indicates that both potently inhibit FicD-mediated AMPylation and deAMPylation. The crystal structure of FicD bound to farnesyl-pyrophosphate demonstrates a competitive inhibition mechanism, with the pyrophosphate adopting the alpha and beta phosphate positions of adenosine triphosphate (ATP) and the hydrocarbon chain filling the nucleoside pocket. FicD variants previously appeared as biochemically indistinguishable, yet lead to different human pathologies. We demonstrate farnesyl-pyrophosphate inhibits FicD and FicD variants implicated in causing hereditary spastic paraplegia, but not the FicD variant associated with neonatal diabetes. This study furthers our understanding of FicD inhibitors and distinguishes disease causing variants, providing insight into pharmacological targeting of UPR activity. - Source: PubMed
Publication date: 2026/03/04
Blevins Aubrie MPeng WeiKinch Lisa NMonshad ZihanParedes Andrea GVolz ChristinaRutter JaredCasey Amanda KHicks Kevin GOrth Kim - Post-translational protein modifications (PTMs) are fundamentally important in regulating protein function across species. One such PTM, referred to as protein AMPylation, is increasingly recognized to fine-tune endoplasmic reticulum (ER) stress signaling in metazoans. Protein AMPylation in the ER is catalyzed by conserved fic-domain containing enzymes (fic AMPylases), including FICD (Homo sapiens) and FIC-1 (Caenorhabditis elegans). However, it remains unclear whether enhanced fic AMPylase-mediated protein AMPylation promotes a conserved cellular response. In this study, we determined the transcriptomic consequences of increased fic AMPylase-mediated protein AMPylation in mouse fibroblasts and young adult nematodes. We find that in C. elegans, FIC-1(E274G) over-expression (OE) triggers a unique transcriptional signature, leading to the marked upregulation of pathways involved in cellular stress signaling. We further show that FIC-1(E274G) OE upregulates genes involved in antibacterial innate immune responses and identify a potentially co-regulated gene cluster sensitive to changes in AMPylation levels. Intriguingly, we observe a similar transcriptomic signature in mouse fibroblasts in response to FICD(E234G) OE. A cross-species comparison of the transcriptomes of nematodes, yeast, and mouse fibroblasts enduring increased fic AMPylase-mediated protein AMPylation revealed a conserved transcriptional core response to enhanced AMPylation. Collectively, this study defines a conserved cellular stress response to enhanced fic AMPylase-mediated protein AMPylation. - Source: PubMed
Publication date: 2026/02/06
Hernandez-Lima Mirella AMariner Blaise LGiblin WilliamMcCormick Mark ATruttmann Matthias C - The Frailty Index of Cumulative Deficits (FI-CD) is a key predictor of adverse health outcomes in older adults, but its utility for cross-study comparisons is limited due to assumptions of item homogeneity. - Source: PubMed
Liu ShuaiRan GuangquanWang YanZhang JieyuanLiu Danping