40S ribosomal protein S3 (RPS3)
The protein contains 243 amino acids for an estimated molecular weight of 26688 Da.
Involved in translation as a component of the 40S small ribosomal subunit (PubMed:8706699). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (PubMed:15707971). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Has also been shown to bind with similar affinity to intact and damaged DNA (PubMed:18610840). Stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571). Enhances the uracil excision activity of UNG1 (PubMed:18973764). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (PubMed:18045535). Represses its own translation by binding to its cognate mRNA (PubMed:20217897). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). Involved in spindle formation and chromosome movement dur (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Apoptotic process
Cell division
Cellular protein metabolic process
Cellular response to DNA damage stimulus
Cellular response to hydrogen peroxide
Cellular response to reactive oxygen species
Cellular response to tumor necrosis factor
Chromosome segregation
Cytoplasmic translation
DNA catabolic process, endonucleolytic
DNA damage response, detection of DNA damage
DNA repair
Gene expression
Mitotic nuclear division
Negative regulation of DNA repair
Negative regulation of protein ubiquitination
Negative regulation of translation
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Positive regulation of activated T cell proliferation
Positive regulation of apoptotic signaling pathway
Positive regulation of base-excision repair
Positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis
Positive regulation of DNA N-glycosylase activity
Positive regulation of DNA repair
Positive regulation of endodeoxyribonuclease activity
Positive regulation of gene expression
Positive regulation of interleukin-2 production
Positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage
Positive regulation of JUN kinase activity
Positive regulation of microtubule polymerization
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of protein-containing complex assembly
Positive regulation of T cell receptor signaling pathway
Regulation of apoptotic process
Regulation of translation
Response to oxidative stress
Response to TNF agonist
RRNA processing
Spindle assembly
SRP-dependent cotranslational protein targeting to membrane
Transcription, DNA-templated
Translation
Translational elongation
Translational initiation
Translational termination
Viral life cycle
Viral process
Viral transcription
Cellular Component
Cytoplasm
Cytosol
Cytosolic ribosome
Cytosolic small ribosomal subunit
Endoplasmic reticulum
Extracellular exosome
Extracellular matrix
Focal adhesion
Intracellular ribonucleoprotein complex
Membrane
Mitochondrial inner membrane
Mitochondrial matrix
Mitotic spindle
NF-kappaB complex
Nucleolus
Nucleoplasm
Nucleus
Plasma membrane
Polysome
Postsynaptic density
Ribonucleoprotein complex
Ribosome
Ruffle membrane
Spindle
Molecular Function
Class I DNA-(apurinic or apyrimidinic site) endonuclease activity
Class III/IV DNA-(apurinic or apyrimidinic site) endonuclease activity
Damaged DNA binding
DNA binding
DNA-(apurinic or apyrimidinic site) endonuclease activity
Endodeoxyribonuclease activity
Enzyme binding
Hsp70 protein binding
Hsp90 protein binding
Iron-sulfur cluster binding
Kinase binding
Microtubule binding
MRNA binding
NF-kappaB binding
Oxidized purine DNA binding
Oxidized purine nucleobase lesion DNA N-glycosylase activity
Oxidized pyrimidine DNA binding
Poly(A) RNA binding
Protein complex binding
Protein kinase A binding
Protein kinase binding
Protein-containing complex binding
RNA binding
Small ribosomal subunit rRNA binding
Structural constituent of ribosome
Supercoiled DNA binding
Transcription factor binding
Tubulin binding
Ubiquitin-like protein conjugating enzyme binding
The reference OMIM entry for this protein is 600454
Ribosomal protein s3; rps3
DESCRIPTION
The ribosomal protein S3 has 2 apparently distinct functions: (1) as a ribosomal protein, RPS3 contributes to the domain of the ribosome where translation is initiated, and (2) as an endonuclease, RPS3 apparently participates in repair of UV damage. Moreover, the first intron of human RPS3 transcripts is processed to generate U15A (600455), a small nucleolar RNA ('snoRNA') (Tycowski et al., 1993). Thus, this is an example of nested genes or a gene within a gene (summary by Polakiewicz et al., 1995).CLONING
Zhang et al. (1990) isolated a human epithelial cDNA encoding RPS3. The deduced RPS3 protein has 243 amino acids. Northern blot analysis indicated that RPS3 is expressed as an approximately 900-bp transcript. To search for genes whose level of expression changes during tumorigenesis, Pogue-Geile et al. (1991) screened a cDNA library derived from a colon adenocarcinoma with cDNAs prepared from the carcinoma and from adjacent normal mucosa. They isolated cDNAs encoding RPS3. Northern blot analysis detected a 1-kb RPS3 transcript which was more abundant in 8 of 8 colon adenocarcinomas and 7 of 10 adenomatous polyps relative to adjacent normal colonic mucosa. The predicted RPS3 protein had no obvious structural motifs. The human and rat RPS3 coding sequences are 90% identical, and the encoded proteins differ by only 1 amino acid.MAPPING
By a combination of somatic cell hybrid analysis, fluorescence in situ hybridization, and YAC/STS content mapping, Polakiewicz et al. (1995) demonstrated that the RPS3/U15A genes map to the immediate vicinity of D11S356 and D11S533 on 11q13.3-q13.5. Kenmochi et al. (1998) confirmed the mapping assignment reported by Polakiewicz et al. (1995). ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 16, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 26, 2017: Protein entry updated
Automatic update: model status changed
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 600454 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed