Table 2.
List of up– and downregulated proteins in VCP–mutant fibroblasts treated with arimoclomol. The term entry reflects UniProt identification number.
| Accession | Protein Name | Fold Change | p–Value | Function |
|---|---|---|---|---|
| Upregulated upon Arimoclomol–Treatment | ||||
| O95786 | Probable ATP–dependent RNA helicase DDX58 | 8.10 | 0.039 | activates expression of IFN–alpha and IFN–beta interferons and recruits E3 ubiquitin–protein ligases |
| O14879 | Interferon–induced protein with tetratricopeptide repeats 3 | 7.40 | 0.020 | can negatively regulate the apoptotic effects |
| P32455 | Guanylate–binding protein 1 | 5.55 | 0.008 | interaction with ubiquitin–binding protein SQSTM1, which delivers monoubiquitylated proteins to autolysosomes |
| Q15043 | Zinc transporter ZIP14 | 4.47 | 0.001 | regulates insulin receptor signalling, glucose uptake, glycogen synthesis and gluconeogenesis |
| Q03519 | Antigen peptide transporter 2 | 3.97 | 0.006 | typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG–induced immunoproteasome |
| P61601 | Neurocalcin–delta | 3.81 | 0.041 | calcium–dependent regulation of rhodopsin phosphorylation |
| P31350 | Ribonucleoside–diphosphate reductase subunit M2 | 3.74 | 0.001 | catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides and inhibits Wnt signaling |
| Q460N5 | Poly [ADP–ribose] polymerase 14 | 3.72 | 0.010 | regulates pro–inflammatory cytokine production in macrophages in response to IFNG stimulation |
| P02794 | Ferritin heavy chain | 3.32 | 0.000 | stores iron in a soluble, non–toxic, readily available form |
| O95379 | Tumor necrosis factor alpha–induced protein 8 | 3.23 | 0.004 | suppresses the TNF–mediated apoptosis by inhibiting caspase–8 activity |
| Q8IYM9 | E3 ubiquitin–protein ligase TRIM22 | 2.97 | 0.003 | interferon–induced antiviral protein with E3 ubiquitin–protein ligase activity |
| P24821 | Tenascin | 2.85 | 0.001 | implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration |
| Q9Y508 | E3 ubiquitin–protein ligase RNF114 | 2.81 | 0.000 | E3 ubiquitin–protein ligase that promotes the ubiquitination of various substrates |
| P48681 | Nestin | 2.56 | 0.045 | required for survival, renewal and mitogen–stimulated proliferation of neural progenitor cells |
| P28838 | Cytosol aminopeptidase | 2.47 | 0.002 | involved in the metabolism of glutathione and in the degradation of glutathione S–conjugates, |
| Q8TCS8 | Polyribonucleotide nucleotidyltransferase 1, mitochondrial | 2.45 | 0.003 | plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels |
| Q9NR77 | Peroxisomal membrane protein 2 | 2.42 | 0.008 | contributes to the unspecific permeability of the peroxisomal membrane |
| Q06330 | Recombining binding protein suppressor of hairless | 2.34 | 0.041 | transcriptional regulator that plays a central role in Notch signaling |
| Q9BQE5 | Apolipoprotein L2 | 2.33 | 0.000 | modulates movement of lipids in the cytoplasm or allows the binding of lipids to organelles |
| P01116 | GTPase KRas | 2.25 | 0.005 | plays an important role in the regulation of cell proliferation |
| P41226 | Ubiquitin–like modifier–activating enzyme 7 | 2.21 | 0.001 | activates ubiquitin by first adenylating with ATP its C–terminal glycine residue |
| Q9Y547 | Intraflagellar transport protein 25 homolog | 2.18 | 0.011 | component of the IFT complex B required for sonic hedgehog/SHH signaling |
| Q99836 | Myeloid differentiation primary response protein MyD88 | 2.16 | 0.006 | adapter protein involved in the Toll–like receptor and IL–1 receptor signaling pathway in the innate immune response |
| Q5D862 | Filaggrin–2 | 2.15 | 0.007 | essential for normal cell–cell adhesion in the cornified cell layers |
| Q9P258 | Protein RCC2 | 2.15 | 0.001 | multifunctional protein that may affect its functions by regulating the activity of small GTPases, such as RAC1 and RALA |
| O94808 | Glutamine––fructose–6–phosphate aminotransferase [isomerizing] 2 | 2.14 | 0.015 | controls the flux of glucose into the hexosamine pathway |
| Q96T88 | E3 ubiquitin–protein ligase UHRF1 | 2.14 | 0.025 | E3 ubiquitin–protein ligase activity by mediating the ubiquitination of target proteins |
| P19474 | E3 ubiquitin–protein ligase TRIM21 | 2.09 | 0.000 | E3 ubiquitin–protein ligase whose activity is dependent on E2 enzymes |
| P33908 | Mannosyl–oligosaccharide 1,2–alpha–mannosidase IA | 2.07 | 0.016 | involved in the maturation of Asn–linked oligosaccharides |
| Q08AF3 | Schlafen family member 5 | 2.07 | 0.002 | plays a role in hematopoietic cell differentiation |
| P52434 | DNA–directed RNA polymerases I, II, and III subunit RPABC3 | 2.03 | 0.003 | DNA–dependent RNA polymerase catalyzes the transcription of DNA into RNA |
| P54105 | Methylosome subunit pICln | 2.02 | 0.021 | chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins |
| O43598 | 2’–deoxynucleoside 5’–phosphate N–hydrolase 1 | 2.02 | 0.001 | catalyzes the cleavage of the N–glycosidic bond of deoxyribonucleoside 5’–monophosphates to yield deoxyribose 5–phosphate |
| O60879 | Protein diaphanous homolog 2 | 2.02 | 0.006 | involved in the regulation of endosome dynamics |
| Q8NFH5 | Nucleoporin NUP35 | 2.01 | 0.000 | functions as a component of the nuclear pore complex |
| Downregulated upon arimoclomol–treatment | ||||
| Q7Z7M9 | Polypeptide N–acetylgalactosaminyltransferase 5 | 0.50 | 0.001 | catalyzes the initial reaction in O–linked oligosaccharide biosynthesis |
| Q16706 | Alpha–mannosidase 2 | 0.49 | 0.000 | catalyzes the first committed step in the biosynthesis of complex N–glycans |
| P02511 | Alpha–crystallin B chain | 0.48 | 0.036 | has chaperone–like activity, preventing aggregation of various proteins under a wide range of stress conditions |
| Q9Y2G5 | GDP–fucose protein O–fucosyltransferase 2 | 0.47 | 0.000 | catalyzes the reaction that attaches fucose through an O–glycosidic linkage to a conserved serine or threonine residue |
| O14494 | Phospholipid phosphatase 1 | 0.44 | 0.001 | regulates phospholipid–mediated signaling pathways |
| O60637 | Tetraspanin–3 | 0.32 | 0.002 | regulates the proliferation and migration of oligodendrocytes |
| P01023 | Alpha–2–macroglobulin | 0.19 | 0.045 | inhibits all four classes of proteinases by a unique ‘trapping’ mechanism |