60S ribosomal protein L11 (RPL11)
The protein contains 178 amino acids for an estimated molecular weight of 20252 Da.
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:19061985, PubMed:12962325, PubMed:24120868). It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:24120868). Promotes nucleolar location of PML (By similarity). (updated: Jan. 31, 2018)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
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| Variant | Description |
|---|---|
| DBA7 |
Biological Process
Cellular protein metabolic process
Cytoplasmic translation
Gene expression
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Negative regulation of protein neddylation
Negative regulation of ubiquitin protein ligase activity
Negative regulation of ubiquitin-dependent protein catabolic process
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Positive regulation of gene expression
Positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator
Positive regulation of protein binding
Protein localization to nucleus
Protein stabilization
Protein targeting
Regulation of signal transduction by p53 class mediator
Ribosomal large subunit assembly
Ribosomal large subunit biogenesis
RRNA processing
SRP-dependent cotranslational protein targeting to membrane
Translation
Translational elongation
Translational initiation
Translational termination
Viral life cycle
Viral process
Viral transcription
The reference OMIM entry for this protein is 604175
Ribosomal protein l11; rpl11
DESCRIPTION
The mammalian ribosome is composed of 4 RNA species (see 180450) and approximately 80 different proteins (see 180466), including RPL11 (Kenmochi et al., 1998).CLONING
Using PCR, Mishin et al. (1995) isolated a human placenta cDNA encoding RPL11. The deduced RPL11 protein has 178 amino acids.GENE STRUCTURE
Boria et al. (2010) stated that the RPL11 gene contains 6 exons spanning 4.6 kb.MAPPING
By somatic cell hybrid and radiation hybrid mapping analyses, Kenmochi et al. (1998) mapped the human RPL11 gene to chromosome 1p. Graphodatsky et al. (1999) localized the RPL11 gene to chromosome 1p36.1-p35 using FISH.GENE FUNCTION
Impeding ribosomal biogenesis generates ribosomal stress that activates p53 (TP53; 191170) to stop cell growth. Dai et al. (2006) stated that ribosomal proteins L5 (RPL5; 603634), L11, and L23 (RPL23; 603662) interact with MDM2 (164785) and inhibit MDM2-mediated p53 ubiquitination and degradation in response to ribosomal stress. They found that L5 and L23 inhibited MDM2 autoubiquitination and MDM2-mediated ubiquitination of p53 in human cell lines. In contrast, L11 increased the cellular level of ubiquitinated MDM2 and stabilized p53. These effects required the autoubiquitination activity of MDM2 and involved direct binding of L11 to MDM2 via its central MDM2-binding domain. Fumagalli et al. (2009) showed that RPL11-mediated p53 induction in human cell lines was a general response to inhibition of 40S or 60S ribosome biogenesis and did not require nucleolar disruption. Inhibition of 40S ribosome biogenesis led to increased ribosome-free RPL11 due to derepression of the polypyrimidine tract at its 5-prime transcriptional start site (the 5-prime TOP), followed by increased RPL11 mRNA translation. Fumagalli et al. (2009) hypothesized that impairment of the assembly of RPL11 into nascent 60S ribosomes allows excess RPL11 to inhibit MDM2 and stabilize p53. In contrast, when 40S ribosome biogenesis is impaired, 60S ribosome biogenesis continues, leading to translational upregulation of mRNAs with 5-prime TOPs, including that for RPL11, despite inhibition of global protein synthesis. Sasaki et al. (2011) found that conditional deletion of Pict1 (GLTSCR2; 605691) expression in mouse embryonic stem (ES) cells inhibited cell growth due to cell cycle arrest and enhanced apoptosis. Mass spectrometric analysis of peptides that immunoprecipitated with epitope-tagged PICT1 in transfected 293T cells showed that PICT1 interacted with RPL11. Knockdown of Pict1 in mouse ES cells resulted in translocation of Rpl11 from the nucleolus to the nucleoplasm, permitting its interaction with Mdm2 and inhibition of p53 ubiquitination. Sasaki et al. (2011) concluded that PICT1 is a potent regulator of the MDM2-p53 pathway.MOLECULAR GENETICS
Gazda et al. (2008) screened 196 probands with Diamond-Blackfan anemia (see DBA7, 612562) for mutations in 25 genes encoding ribosomal proteins and identified 11 different mutations in the RPL11 gene in 13 probands and 5 additional family members (see, e.g., 604175.0001-604175.0004). The mutations segregated with disease in multiplex families and were not found in at least 150 controls. Analysis of pre-rRNAs from lymphoblastoid cells established from DBA patients revealed accumulation of 32S and 12S pre-rRNA as well as smaller precursors of 5.8S rRNA compared to controls, indicating defective maturation of internal transcribed space ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 604175 was added.