Peptide name : Reactive oxygen species modulator 1

Source/Organism : Human

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 79

C-terminal modification: Not found

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Antibody-based assay

Assay time : 48h

Activity : Not found

Cell line : HeLa

Cancer type : Not specified

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 8182.7931 Dalton

Aliphatic index : 0.605

Instability index : 50.6494

Hydrophobicity (GRAVY) : 0.5101

Isoelectric point : 9.5767

Charge (pH 7) : 4.4616

Aromaticity : 0.088

Molar extinction coefficient (cysteine, cystine): (1490, 1740)

Hydrophobic/hydrophilic ratio : 2.76190476

hydrophobic moment : -0.023

Missing amino acid : N,W,H

Most occurring amino acid : G

Most occurring amino acid frequency : 17

Least occurring amino acid : Y

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0.3, 0.2)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)CNC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CS)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCSC)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O

1 : Li J, et al. Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins. Mol Cell Proteomics. 2010; 9:2517-28. doi: 10.1074/mcp.M110.001719

2 : Hwang IT, et al. Drug resistance to 5-FU linked to reactive oxygen species modulator 1. Biochem Biophys Res Commun. 2007; 359:304-10. doi: 10.1016/j.bbrc.2007.05.088

3 : Deloukas P, et al. The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001; 414:865-71. doi: 10.1038/414865a

4 : Burkard TR, et al. Initial characterization of the human central proteome. BMC Syst Biol. 2011; 5:17. doi: 10.1186/1752-0509-5-17

5 : Chung YM, et al. A novel protein, Romo1, induces ROS production in the mitochondria. Biochem Biophys Res Commun. 2006; 347:649-55. doi: 10.1016/j.bbrc.2006.06.140

6 : Chung YM, et al. Replicative senescence induced by Romo1-derived reactive oxygen species. J Biol Chem. 2008; 283:33763-71. doi: 10.1074/jbc.M805334200

7 : Gerhard DS, et al. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004; 14:2121-7. doi: 10.1101/gr.2596504

8 : Na AR, et al. A critical role for Romo1-derived ROS in cell proliferation. Biochem Biophys Res Commun. 2008; 369:672-8. doi: 10.1016/j.bbrc.2008.02.098

9 : Zhao J, et al. The novel conserved mitochondrial inner-membrane protein MTGM regulates mitochondrial morphology and cell proliferation. J Cell Sci. 2009; 122:2252-62. doi: 10.1242/jcs.038513

10 : Sang A, et al. Upregulation of SYF2 Relates to Retinal Ganglion Cell Apoptosis and Retinal Glia Cell Proliferation After Light-Induced Retinal Damage. J Mol Neurosci. 2015; 56:480-90. doi: 10.1007/s12031-015-0534-5

11 : Van Damme P, et al. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012; 109:12449-54. doi: 10.1073/pnas.1210303109

12 : Sha J, et al. Antibacterial potential of hGlyrichin encoded by a human gene. J Pept Sci. 2012; 18:97-104. doi: 10.1002/psc.1421

Paper title : Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins.

Doi : https://doi.org/10.1074/mcp.M110.001719

Abstract : The mammalian spermatozoon has many cellular compartments, such as head and tail, permitting it to interact with the female reproductive tract and fertilize the egg. It acquires this fertilizing potential during transit through the epididymis, which secretes proteins that coat different sperm domains. Optimal levels of these proteins provide the spermatozoon with its ability to move to, bind to, fuse with, and penetrate the egg; otherwise male infertility results. As few human epididymal proteins have been characterized, this work was performed to generate a database of human epididymal sperm-located proteins involved in maturation. Two-dimensional gel electrophoresis of epididymal tissue and luminal fluid proteins, followed by identification using MALDI-TOF/MS or MALDI-TOF/TOF, revealed over a thousand spots in gels comprising 745 abundant nonstructural proteins, 408 in luminal fluids, of which 207 were present on spermatozoa. Antibodies raised to 619 recombinant or synthetic peptides, used in Western blots, histological sections, and washed sperm preparations to confirm antibody quality and protein expression, indicated their regional location in the epididymal epithelium and highly specific locations on washed functional spermatozoa. Sperm function tests suggested the role of some proteins in motility and protection against oxidative attack. A large database of these proteins, characterized by size, pI, chromosomal location, and function, was given a unified terminology reflecting their sperm domain location. These novel, secreted human epididymal proteins are potential targets for a posttesticular contraceptive acting to provide rapid, reversible, functional sterility in men and they are also biomarkers that could be used in noninvasive assessments of male fertility.

Paper title : Drug resistance to 5-FU linked to reactive oxygen species modulator 1.

Doi : https://doi.org/10.1016/j.bbrc.2007.05.088

Abstract : While acute oxidative stress triggers cell apoptosis or necrosis, persistent oxidative stress induces genomic instability and has been implicated in tumor progression and drug resistance. In a previous report, we demonstrated that reactive oxygen species modulator 1 (Romo1) expression was up-regulated in most cancer cell lines and suggested that increased Romo1 expression might confer chronic oxidative stress to tumor cells. In this study, we show that enforced Romo1 expression induces reactive oxygen species (ROS) production in the mitochondria leading to massive cell death. However, tumor cells that adapt to oxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, and Bcl-2 showed drug resistance to 5-FU. To elucidate the relationship between 5-FU-induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit 5-FU-triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked 5-FU-induced ROS generation, demonstrating that 5-FU treatment stimulated ROS production through Romo1 induction. Based on these results we suggest that cellular adaptive response to Romo1-induced ROS is another mechanism of drug resistance to 5-FU and Romo1 expression may provide a new clinical implication in drug resistance of cancer chemotherapy.

Paper title : The DNA sequence and comparative analysis of human chromosome 20.

Doi : https://doi.org/10.1038/414865a

Abstract : The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

Paper title : Initial characterization of the human central proteome.

Doi : https://doi.org/10.1186/1752-0509-5-17

Abstract : BACKGROUND: On the basis of large proteomics datasets measured from seven human cell lines we consider their intersection as an approximation of the human central proteome, which is the set of proteins ubiquitously expressed in all human cells. Composition and properties of the central proteome are investigated through bioinformatics analyses. RESULTS: We experimentally identify a central proteome comprising 1,124 proteins that are ubiquitously and abundantly expressed in human cells using state of the art mass spectrometry and protein identification bioinformatics. The main represented functions are proteostasis, primary metabolism and proliferation. We further characterize the central proteome considering gene structures, conservation, interaction networks, pathways, drug targets, and coordination of biological processes. Among other new findings, we show that the central proteome is encoded by exon-rich genes, indicating an increased regulatory flexibility through alternative splicing to adapt to multiple environments, and that the protein interaction network linking the central proteome is very efficient for synchronizing translation with other biological processes. Surprisingly, at least 10% of the central proteome has no or very limited functional annotation. CONCLUSIONS: Our data and analysis provide a new and deeper description of the human central proteome compared to previous results thereby extending and complementing our knowledge of commonly expressed human proteins. All the data are made publicly available to help other researchers who, for instance, need to compare or link focused datasets to a common background.

Paper title : A novel protein, Romo1, induces ROS production in the mitochondria.

Doi : https://doi.org/10.1016/j.bbrc.2006.06.140

Abstract : The majority of endogenous reactive oxygen species (ROS) are produced in the mitochondrial respiratory chain. An imbalance in ROS production alters the intracellular redox homeostasis, triggers DNA damage, and contributes to cancer development and progression. This study identified a novel protein, reactive oxygen species modulator 1 (Romo1), which is localized in the mitochondria. Romo1 was found to increase the level of ROS in the cells. Increased Romo1 expression was observed in various cancer cell lines. This suggests that the increased Romo1 expression during cancer progression may cause persistent oxidative stress to tumor cells, which can increase their malignancy.

Paper title : Replicative senescence induced by Romo1-derived reactive oxygen species.

Doi : https://doi.org/10.1074/jbc.M805334200

Abstract : Persistent accumulation of DNA damage induced by reactive oxygen species (ROS) is proposed to be a major contributor toward the aging process. Furthermore, an increase in age-associated ROS is strongly correlated with aging in various species, including humans. Here we showed that the enforced expression of the ROS modulator 1 (Romo1) triggered premature senescence by ROS production, and this also contributed toward induction of DNA damage. Romo1-derived ROS was found to originate in the mitochondrial electron transport chain. Romo1 expression gradually increased in proportion to population doublings of IMR-90 human fibroblasts. An increase in ROS production in these cells with high population doubling was blocked by the Romo1 knockdown using Romo1 small interfering RNA. Romo1 knockdown also inhibited the progression of replicative senescence. Based on these results, we suggest that age-related ROS levels increase, and this contributes to replicative senescence, which is directly associated with Romo1 expression.

Paper title : The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

Doi : https://doi.org/10.1101/gr.2596504

Abstract : The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

Paper title : A critical role for Romo1-derived ROS in cell proliferation.

Doi : https://doi.org/10.1016/j.bbrc.2008.02.098

Abstract : Low levels of endogenous reactive oxygen species (ROS) originating from NADPH oxidase have been implicated in various signaling pathways induced by growth factors and mediated by cytokines. However, the main source of ROS is known to be the mitochondria, and increased levels of ROS from the mitochondria have been observed in many cancer cells. Thus far, the mechanism of ROS production in cancer cell proliferation in the mitochondria is not well-understood. We recently identified a novel protein, ROS modulator 1 (Romo1), and reported that increased expression of Romo1-triggered ROS production in the mitochondria. The experiments conducted in the present study showed that Romo1-derived ROS were indispensable for the proliferation of both normal and cancer cells. Furthermore, whilst cell growth was inhibited by blocking the ERK pathway in cells transfected with siRNA directed against Romo1, the cell growth was recovered by addition of exogenous hydrogen peroxide. The results of this study suggest that Romo1-induced ROS may play an important role in redox signaling in cancer cells.

Paper title : The novel conserved mitochondrial inner-membrane protein MTGM regulates mitochondrial morphology and cell proliferation.

Doi : https://doi.org/10.1242/jcs.038513

Abstract : Although several proteins involved in mediating mitochondrial division have been reported in mammals, the mechanism of the fission machinery remains to be elucidated. Here, we identified a human nuclear gene (named MTGM) that encodes a novel, small, integral mitochondrial inner-membrane protein and shows high expression in both human brain tumor cell lines and tumor tissues. The gene is evolutionarily highly conserved, and its orthologs are 100% identical at the amino acid level in all analyzed mammalian species. The gene product is characterized by an unusual tetrad of the GxxxG motif in the transmembrane segment. Overexpression of MTGM (mitochondrial targeting GxxxG motif) protein results in mitochondrial fragmentation and release of mitochondrial Smac/Diablo to the cytosol with no effect on apoptosis. MTGM-induced mitochondrial fission can be blocked by a dominant negative Drp1 mutant (Drp1-K38A). Overexpression of MTGM also results in inhibition of cell proliferation, stalling of cells in S phase and nuclear accumulation of gamma-H2AX. Knockdown of MTGM by RNA interference induces mitochondrial elongation, an increase of cell proliferation and inhibition of cell death induced by apoptotic stimuli. In conclusion, we suggest that MTGM is an integral mitochondrial inner-membrane protein that coordinately regulates mitochondrial morphology and cell proliferation.

Paper title : Upregulation of SYF2 Relates to Retinal Ganglion Cell Apoptosis and Retinal Glia Cell Proliferation After Light-Induced Retinal Damage.

Doi : https://doi.org/10.1007/s12031-015-0534-5

Abstract : SYF2 (SYF2 homologue, RNA splicing factor), also known as CCNDBP1-interactor or p29, belongs to the SYF2 family, which are involved in pre-mRNA splicing and cell cycle progression. Accumulating evidences demonstrate that SYF2 exerted multiple effects including pro-apoptosis, cell differentiation, and glial activation in the pathogenesis of various experimental central nervous system (CNS) diseases. However, SYF2 expression and functions in the retina are still with limited acquaintance. To investigate whether SYF2 was involved in retinal degeneration, we performed a light-induced retinal damage model in adult rats. The SYF2 protein expression was dramatically upregulated after retinal damage. Besides that, SYF2 localized in the retinal ganglion cell (RGC) layer (GCL), inner unclear layer (INL), and outer nuclear layer (ONL) after light exposure. In addition, the expression of cyclin D1, CDK4, and active caspase-3 was parallel with SYF2. We also found the co-localization of SYF2 with active caspase-3, PCNA, and CD11b. Collectively, SYF2 might participate in RGC apoptosis and retinal glia cell proliferation after light-induced retinal damage.

Paper title : N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

Doi : https://doi.org/10.1073/pnas.1210303109

Abstract : Protein N-terminal acetylation (Nt-acetylation) is an important mediator of protein function, stability, sorting, and localization. Although the responsible enzymes are thought to be fairly well characterized, the lack of identified in vivo substrates, the occurrence of Nt-acetylation substrates displaying yet uncharacterized N-terminal acetyltransferase (NAT) specificities, and emerging evidence of posttranslational Nt-acetylation, necessitate the use of genetic models and quantitative proteomics. NatB, which targets Met-Glu-, Met-Asp-, and Met-Asn-starting protein N termini, is presumed to Nt-acetylate 15% of all yeast and 18% of all human proteins. We here report on the evolutionary traits of NatB from yeast to human and demonstrate that ectopically expressed hNatB in a yNatB-Δ yeast strain partially complements the natB-Δ phenotypes and partially restores the yNatB Nt-acetylome. Overall, combining quantitative N-terminomics with yeast studies and knockdown of hNatB in human cell lines, led to the unambiguous identification of 180 human and 110 yeast NatB substrates. Interestingly, these substrates included Met-Gln- N-termini, which are thus now classified as in vivo NatB substrates. We also demonstrate the requirement of hNatB activity for maintaining the structure and function of actomyosin fibers and for proper cellular migration. In addition, expression of tropomyosin-1 restored the altered focal adhesions and cellular migration defects observed in hNatB-depleted HeLa cells, indicative for the conserved link between NatB, tropomyosin, and actin cable function from yeast to human.

Paper title : Antibacterial potential of hGlyrichin encoded by a human gene.

Doi : https://doi.org/10.1002/psc.1421

Abstract : Emerging multidrug-resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero-immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin-resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42-60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero-immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide.