Ask about this productRelated genes to: RSAD1 Blocking Peptide
- Gene:
- RSAD1 NIH gene
- Name:
- radical S-adenosyl methionine domain containing 1
- Previous symbol:
- -
- Synonyms:
- FLJ11164, HemW
- Chromosome:
- 17q21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2004-11-08
- Date modifiied:
- 2019-03-19
Related products to: RSAD1 Blocking Peptide
Related articles to: RSAD1 Blocking Peptide
- Human radical S-adenosyl-l-methionine domain-containing 1 (hRSAD1) is a recently discovered mitochondrial protein that plays an important yet not fully understood role in cellular function. hRSAD1 belongs to the large and diverse radical S-adenosyl-l-methionine (SAM) superfamily of enzymes that utilize a redox-active [4Fe-4S] cluster and SAM to initiate radical catalysis. In addition, hRSAD1 harbors a putative heme-binding domain. hRSAD1 was expressed in E. coli and purified to homogeneity. The purified hRSAD1 was reconstituted with a [4Fe-4S] cluster that could be reduced to the [4Fe-4S] state, and was characterized using UV-visible and EPR spectroscopy. The ability of hRSAD1 to bind porphyrins was evaluated, revealing that protoporphyrin IX (PPIX) and its metal analogs, including Fe-PPIX, Fe-PPIX, and Zn-PPIX, bind to the reconstituted hRSAD1-[4Fe-4S] protein. The association constant (K) for Fe-PPIX was determined using UV-visible and fluorescence spectroscopy to be (1.6 ± 0.3) × 10 M. Additionally, the hRSAD1-[4Fe-4S]-heme complex binds oxygen, carbon monoxide, and cyanide. These findings suggest that hRSAD1 may play a significant role in heme-related metabolic processes. - Source: PubMed
Publication date: 2026/02/12
Zadvornyy Oleg ADrobizhev MikhailTokmina-Lukaszewska MonikaShepard Eric MBroderick William EBroderick Joan B - Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer's disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 () and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. vs genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals. - Source: PubMed
York AudraEverhart AngelaVitek Michael PGottschalk Kirby WColton Carol A - Chronic central serous chorioretinopathy (cCSC) is a multifactorial eye disease characterized by subretinal fluid accumulation that leads to vision loss. Clinically, cCSC is associated with stress, hypercortisolism and corticosteroid use, and is more frequent in males (80%) than in females (20%). Current genetic studies on cCSC have thus far focussed on common variants, but familial occurrence of cCSC also suggests a role for rare variants in the disease susceptibility. Therefore, in this study, we performed exome sequencing of cCSC patients to elucidate the role of rare (protein-altering) variants in the disease. Exome sequencing was performed on 269 cCSC patients and 1,586 controls. Data were processed according to the Genome-Analysis-Toolkit (GATK) best practices. Principal component analysis was performed to check for genetic ancestry and only unrelated subjects of European descent were retained. Burden, SKAT and SKAT-O tests were performed using 2 different grouping criteria. One group included protein-altering variants only, while the other contained synonymous and splice site variants as well. The gene-based analyses were performed using the SKAT R-package correcting for two principal components using two approaches; (1) on the entire cohort correcting for sex and (2) on males and females separately. Additionally, the gene-based associations of genes at previously reported cCSC loci were investigated. After filtering, the dataset contained 263 cCSC patients (208 males [79%]) and 1352 controls (671 males [50%]) carrying 197,915 protein-altering variants in 16,370 genes and 330,689 exonic variants in 18,173 genes. Analysis stratified by sex identified significant associations with the PIGZ (P = 9.19 × 10 & P = 2.48 × 10), DUOX1 (P = 1.03 × 10), RSAD1 (P = 1.92 × 10 & P = 8.57 × 10) and LAMB3 (P = 1.40 × 10 & P = 1.14 × 10) genes in female cCSC patients, after correction for multiple testing. The number of rare variant carriers in these genes was significantly higher in the female cCSC cohort compared to female controls (45,5% vs. 18.5%, P = 1.92 × 10, OR = 3.67 [95% CI = 2.09-6.46]). No significant associations were identified in the entire cohort nor in the male patients. In this exome study on cCSC patients, we have identified PIGZ, DUOX1, RSAD1 and LAMB3 as potential new candidate genes for cCSC in females. The sex-specific associations identified here suggest a possible interaction between rare genetic factors and sex for cCSC, but replication of these findings in additional cohorts of cCSC patients is necessary. - Source: PubMed
Publication date: 2019/04/29
Schellevis Rosa LBreukink Myrte BGilissen ChristianBoon Camiel J FHoyng Carel Bde Jong Eiko Kden Hollander Anneke I - Radical -adenosylmethionine (SAM) enzymes exist in organisms from all kingdoms of life, and all of these proteins generate an adenosyl radical via the homolytic cleavage of the S-C(5') bond of SAM. Of particular interest are radical SAM enzymes, such as heme chaperones, that insert heme into respiratory enzymes. For example, heme chaperones insert heme into target proteins but have been studied only for the formation of cytochrome -type hemoproteins. Here, we report that a radical SAM protein, the heme chaperone HemW from bacteria, is required for the insertion of heme b into respiratory chain enzymes. As other radical SAM proteins, HemW contains three cysteines and one SAM coordinating an [4Fe-4S] cluster, and we observed one heme per subunit of HemW. We found that an intact iron-sulfur cluster was required for HemW dimerization and HemW-catalyzed heme transfer but not for stable heme binding. A bacterial two-hybrid system screen identified bacterioferritins and the heme-containing subunit NarI of the respiratory nitrate reductase NarGHI as proteins that interact with HemW. We also noted that the bacterioferritins potentially serve as heme donors for HemW. Of note, heme that was covalently bound to HemW was actively transferred to a heme-depleted, catalytically inactive nitrate reductase, restoring its nitrate-reducing enzyme activity. Finally, the human HemW orthologue radical SAM domain-containing 1 (RSAD1) stably bound heme. In conclusion, our findings indicate that the radical SAM protein family HemW/RSAD1 is a heme chaperone catalyzing the insertion of heme into hemoproteins. - Source: PubMed
Publication date: 2017/12/27
Haskamp VeraKarrie SimoneMingers ToniBarthels StefanAlberge FrançoisMagalon AxelMüller KatrinBill EckhardLubitz WolfgangKleeberg KirstinSchweyen PeterBröring MartinJahn MartinaJahn Dieter - Radical S-adenosylmethionine (SAM) enzymes catalyze an astonishing array of complex and chemically challenging reactions across all domains of life. Of approximately 114,000 of these enzymes, 8 are known to be present in humans: MOCS1, molybdenum cofactor biosynthesis; LIAS, lipoic acid biosynthesis; CDK5RAP1, 2-methylthio-N(6)-isopentenyladenosine biosynthesis; CDKAL1, methylthio-N(6)-threonylcarbamoyladenosine biosynthesis; TYW1, wybutosine biosynthesis; ELP3, 5-methoxycarbonylmethyl uridine; and RSAD1 and viperin, both of unknown function. Aberrations in the genes encoding these proteins result in a variety of diseases. In this review, we summarize the biochemical characterization of these 8 radical S-adenosylmethionine enzymes and, in the context of human health, describe the deleterious effects that result from such genetic mutations. - Source: PubMed
Publication date: 2016/05/04
Landgraf Bradley JMcCarthy Erin LBooker Squire J