RPS27 (ribosomal protein S27)

2011-08-01   Tiffany Pierson , Brendan C Stack Jr 

Department of Otolaryngology-Head, Neck Surgery, University of Arkansas for Medical Sciences, AR 72205, USA





The RPS27 gene is comprised of 1.39 kb and consists of 4 exons. This gene is a member of the Human CCDS set: CCDS1059.


The transcript is 350 base pairs long.


Multiple RPS27 pseudogenes are dispersed throughout the genome. The RPS27L pseudogene, located at 15q22.2, is known to encode a protein that shares 96% of its amino acid sequence with RPS27 (Balasubramanian et al., 2009).



RPS27 is a 9461 Da protein composed of 84 amino acids. The protein contains a C4 zinc finger domain, similar to steroid and thyroid hormones, which enables DNA binding. RPS27 is found in both the cytoplasm and the nucleus.


Ubiquitous expression. Expressed at high levels in actively dividing cells and in cancers of ectodermal origin, as well as in melanoma (Fernandez-Pol et al., 1993). When overexpressed, it is secreted into serum (Lee et al., 2004).


1. Component of the 40S ribosomal subunit in the cytoplasm: ribosomes carry out translation of proteins. The eukaryotic ribosome is made up of a small 40S and a large 60S subunit. Together these subunits are comprised of 4 different rRNA species and almost 80 different RPs (ribosomal proteins). As a component of the 40S subunit, RPS27 is found near RPS18 and covalently bound to translation initiation factor eIF3.
2. A mediator of cellular proliferation and survival: expression is induced by a variety of growth factors and other signaling molecules, including TGF-beta and cAMP; RPS27 can bind to cAMP response elements of DNA (Fernandez-Pol et al., 1993).
3. Oncogenesis (see below).


Member of the ribosomal protein S27e family.



Single nucleotide polymorphisms have been identified, but have not been linked to disease.

Implicated in

Entity name
Various carcinomas and melanoma
RPS27 overexpression has been reported in many cancers including prostate cancer (Fernandez-Pol et al., 1997), colorectal cancer (Ganger et al., 1997), liver cancer (Ganger et al., 2001), breast cancer (Atsuta et al., 2002), head and neck squamous cell cancer (HNSCC) (Stack et al., 1999; Stack et al., 2004; Lee et al., 2004), gastric cancer (Wang, et al., 2006), as well as, melanoma (Santa Cruz et al., 1997).
Since high serum levels of RPS27 have been found in cancer patients, especially in head and neck squamous cell carcinoma (HNSCC), the protein can be used as a tumor marker (Fernandez-Pol et al., 1996; Lee et al., 2004; Stack et al. 2004).
It was reported that RPS27 levels correlate with tumor stage in patients with gastric cancer, thus high levels serve as a poor prognostic indicator (Wang et al., 2006).
The mechanism behind RPS27 overexpression is currently under investigation. One explanation recently offered arises from the relationship between RPS27, MDM2 and p53: RPS27 is a p53 repressible protein (He and Sun, 2007; Li et al., 2007). A 2011 study found that it competes with p53 for a central acidic binding domain on MDM2. Once bound, MDM2 is stimulated to ubiquinate and degrade the RPS27 or p53, whichever it is bound to. When RPS27 levels are elevated, it can out-compete p53 for MDM2 binding and subsequent degradation, thus stabilizing p53 levels. This would be an appropriate cellular response to genotoxic stress. The same study also found that mutant p53 cannot suppress RPS27, only the wild-type can. Since mutated p53 is found in almost 50% of all human cancers, RPS27 overexpression logically follows. Furthermore, stabilization of mutant p53 levels associated with RPS27 abundance could provide malignant cells with a growth advantage (Xiong et al., 2011).
RPS27 knockdown was found to enhance spontaneous apoptosis of tumor cells via caspase-3 activation (Wang et al., 2006; Yang et al., 2011).
HNSCC: some have questioned if RPS27 overexpression is the cause or result of cancer. A 2010 study overexpressed RPS27 in a line of HNSCC cells to study the impact on tumor behavior. They found that RPS27 overexpression resulted in reduced cancer cell growth, proliferation rate and angiogenesis. RPS27 overexpression was also found to reduce the mRNA of Paxillin, a focal adhesion protein up regulated in HNSCC and many other cancer cells. RPS27 induced Paxillin repression offers a possible explanation for the decreased HNSCC growth (Dai et al., 2010).


Pubmed IDLast YearTitleAuthors
121755292002Identification of metallopanstimulin-1 as a member of a tumor associated antigen in patients with breast cancer.Atsuta Y et al
191239372009Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes.Balasubramanian S et al
196420982010Extraribosomal function of metallopanstimulin-1: reducing paxillin in head and neck squamous cell carcinoma and inhibiting tumor growth.Dai Y et al
91791901997Expression of metallopanstimulin and oncogenesis in human prostatic carcinoma.Fernandez-Pol JA et al
114252642001Differential expression of metallopanstimulin/S27 ribosomal protein in hepatic regeneration and neoplasia.Ganger DR et al
171109292006MDMX regulation of p53 response to ribosomal stress.Gilkes DM et al
170577332007Ribosomal protein S27L is a direct p53 target that regulates apoptosis.He H et al
154676192004A new assay to screen for head and neck squamous cell carcinoma using the tumor marker metallopanstimulin.Lee WJ et al
180564582007Ribosomal protein S27-like, a p53-inducible modulator of cell fate in response to genotoxic stress.Li J et al
94048501997Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin.Santa Cruz DJ et al
155983482004Metallopanstimulin as a marker for head and neck cancer.Stack BC Jr et al
169145862006In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity.Wang YW et al
211700872011Ribosomal protein S27-like and S27 interplay with p53-MDM2 axis as a target, a substrate and a regulator.Xiong X et al
217966322012Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: the role of apoptosis induction of gastric cancer cells.Yang ZY et al

Other Information

Locus ID:

NCBI: 6232
MIM: 603702
HGNC: 10416
Ensembl: ENSG00000177954


dbSNP: 6232
ClinVar: 6232
TCGA: ENSG00000177954


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Ribosome, eukaryotesKEGGhsa_M00177
Ribosome, eukaryotesKEGGM00177
Metabolism of proteinsREACTOMER-HSA-392499
Eukaryotic Translation InitiationREACTOMER-HSA-72613
Cap-dependent Translation InitiationREACTOMER-HSA-72737
Formation of a pool of free 40S subunitsREACTOMER-HSA-72689
Formation of the ternary complex, and subsequently, the 43S complexREACTOMER-HSA-72695
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43SREACTOMER-HSA-72662
Translation initiation complex formationREACTOMER-HSA-72649
Ribosomal scanning and start codon recognitionREACTOMER-HSA-72702
GTP hydrolysis and joining of the 60S ribosomal subunitREACTOMER-HSA-72706
L13a-mediated translational silencing of Ceruloplasmin expressionREACTOMER-HSA-156827
SRP-dependent cotranslational protein targeting to membraneREACTOMER-HSA-1799339
Eukaryotic Translation ElongationREACTOMER-HSA-156842
Peptide chain elongationREACTOMER-HSA-156902
Eukaryotic Translation TerminationREACTOMER-HSA-72764
Infectious diseaseREACTOMER-HSA-5663205
Influenza InfectionREACTOMER-HSA-168254
Influenza Life CycleREACTOMER-HSA-168255
Influenza Viral RNA Transcription and ReplicationREACTOMER-HSA-168273
Viral mRNA TranslationREACTOMER-HSA-192823
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate ForminsREACTOMER-HSA-5663220
Gene ExpressionREACTOMER-HSA-74160
Nonsense-Mediated Decay (NMD)REACTOMER-HSA-927802
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)REACTOMER-HSA-975957
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)REACTOMER-HSA-975956
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic PrometaphaseREACTOMER-HSA-68877
Resolution of Sister Chromatid CohesionREACTOMER-HSA-2500257
Mitotic Metaphase and AnaphaseREACTOMER-HSA-2555396
Mitotic AnaphaseREACTOMER-HSA-68882
Separation of Sister ChromatidsREACTOMER-HSA-2467813
Metabolism of amino acids and derivativesREACTOMER-HSA-71291
Selenoamino acid metabolismREACTOMER-HSA-2408522
Selenocysteine synthesisREACTOMER-HSA-2408557
rRNA processingREACTOMER-HSA-72312
Major pathway of rRNA processing in the nucleolus and cytosolREACTOMER-HSA-6791226
rRNA processing in the nucleus and cytosolREACTOMER-HSA-8868773


Pubmed IDYearTitleCitations
211700872011Ribosomal protein S27-like and S27 interplay with p53-MDM2 axis as a target, a substrate and a regulator.46
254249022015Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia.34
284415292017Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation.24
249131452014A highly recurrent RPS27 5'UTR mutation in melanoma.22
169145862006In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity.14
217966322012Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: the role of apoptosis induction of gastric cancer cells.10
196420982010Extraribosomal function of metallopanstimulin-1: reducing paxillin in head and neck squamous cell carcinoma and inhibiting tumor growth.7
227985062012Increased serum level of RPMPS-1/S27 protein in patients with various types of cancer is useful for the early detection, prevention and therapy.5
215188172011Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication.4
289418022017CFTR modulates RPS27 gene expression using chloride anion as signaling effector.4


Tiffany Pierson ; Brendan C Stack Jr

RPS27 (ribosomal protein S27)

Atlas Genet Cytogenet Oncol Haematol. 2011-08-01

Online version: http://atlasgeneticsoncology.org/gene/45550/rps27-(ribosomal-protein-s27)