Small ribosomal subunit protein uS3

Function

Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Has endonuclease activity and plays a role in repair of damaged DNA. Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA. Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS). Has also been shown to bind with similar affinity to intact and damaged DNA. Stimulates the N-glycosylase activity of the base excision protein OGG1. Enhances the uracil excision activity of UNG1. Also stimulates the cleavage of the phosphodiester backbone by APEX1. When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage. Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide. 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. Represses its own translation by binding to its cognate mRNA. Binds to and protects TP53/p53 from MDM2-mediated ubiquitination. Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization. Involved in induction of apoptosis through its role in activation of CASP8. Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5. Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation.

Classification

Family (Pfam)

PF07650 KH_2, PF00189 Ribosomal_S3_C

InterPro

KH_dom-like_a/b, KH_dom_type_2, KH_sf_prok-type, Ribosomal_S3_C_sf, Ribosomal_uS3, Ribosomal_uS3_C, Ribosomal_uS3_CS, Ribosomal_uS3_euk_arc

Functional cluster

Archaeal Ribosomal & Replication Proteins

Experimental structures · PDB · 165

• 1WH9 NMR
• 4UG0 EM
• 4V6X EM 5.00A
• 5A2Q EM 3.90A
• 5AJ0 EM 3.50A
• 5FLX EM 3.90A
• 5LKS EM 3.60A
• 5OA3 EM 4.30A
• 5T2C EM 3.60A
• 5VYC X-ray 6.00A
• 6FEC EM 6.30A
• 6G51 EM 4.10A
• … and 153 more

A predicted model is available from AlphaFold.

Gene Ontology · 69

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0022626 cytosolic ribosome
• GO:0022627 cytosolic small ribosomal subunit
• GO:0005783 endoplasmic reticulum
• GO:0070062 extracellular exosome
• GO:0005925 focal adhesion
• GO:0016020 membrane
• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix
• GO:0072686 mitotic spindle
• GO:0071159 NF-kappaB complex
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0014069 postsynaptic density
• GO:1990904 ribonucleoprotein complex
• GO:0005840 ribosome
• GO:0032587 ruffle membrane
• GO:0140078 class I DNA-(apurinic or apyrimidinic site) endonuclease activity
• GO:0003684 damaged DNA binding
• GO:0003677 DNA binding
• GO:0004520 DNA endonuclease activity
• GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0140297 DNA-binding transcription factor binding
• GO:0019899 enzyme binding
• GO:0030544 Hsp70 protein binding
• GO:0051879 Hsp90 protein binding
• GO:0051536 iron-sulfur cluster binding
• GO:0019900 kinase binding
• GO:0008017 microtubule binding
• GO:0003729 mRNA binding
• GO:0032357 oxidized purine DNA binding
• GO:0032358 oxidized pyrimidine DNA binding
• GO:0051018 protein kinase A binding
• GO:0019901 protein kinase binding
• GO:0003723 RNA binding
• GO:0070181 small ribosomal subunit rRNA binding
• GO:0003735 structural constituent of ribosome
• GO:0097100 supercoiled DNA binding
• GO:0015631 tubulin binding
• GO:0044390 ubiquitin-like protein conjugating enzyme binding
• GO:0006915 apoptotic process
• GO:0006284 base-excision repair
• GO:0051301 cell division
• GO:0070301 cellular response to hydrogen peroxide
• GO:0034614 cellular response to reactive oxygen species
• GO:0007059 chromosome segregation
• GO:0002181 cytoplasmic translation
• GO:0002183 cytoplasmic translational initiation
• GO:0006974 DNA damage response
• GO:0006281 DNA repair
• GO:0006351 DNA-templated transcription
• GO:0045738 negative regulation of DNA repair
• GO:0031397 negative regulation of protein ubiquitination
• GO:0017148 negative regulation of translation
• GO:2001235 positive regulation of apoptotic signaling pathway
• GO:1905053 positive regulation of base-excision repair
• GO:0045739 positive regulation of DNA repair
• GO:2000144 positive regulation of DNA-templated transcription initiation
• GO:0010628 positive regulation of gene expression
• GO:1902231 positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage
• GO:0031116 positive regulation of microtubule polymerization
• GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction
• GO:0042981 regulation of apoptotic process
• GO:0061481 response to TNF agonist
• GO:0051225 spindle assembly

Drugs targeting this protein · 2

• CYCLOHEXIMIDE inhibitor
• ATALUREN modulator

Related proteins · sequence + function similarity

• Small ribosomal subunit protein uS3 1.00
• Small ribosomal subunit protein uS3 1.00
• Small ribosomal subunit protein uS3 1.00
• Small ribosomal subunit protein uS3 1.00
• Small ribosomal subunit protein uS3 1.00
• Small ribosomal subunit protein uS3 1.00
• Small ribosomal subunit protein uS3A 0.99
• Small ribosomal subunit protein uS3B 0.99
• Small ribosomal subunit protein uS3 0.98
• Small ribosomal subunit protein uS3 0.98
• Small ribosomal subunit protein uS3 0.95
• Small ribosomal subunit protein uS3 0.93

Co-cited proteins · studied together in the literature

• E3 ubiquitin-protein ligase RNF10 5 shared papers
• Small ribosomal subunit protein uS3 2 shared papers
• Small ribosomal subunit protein uS5 8 shared papers
• Small ribosomal subunit protein uS3 1 shared papers
• Serine/threonine-protein kinase RIO3 2 shared papers
• Small ribosomal subunit protein eS10 5 shared papers
• Small ribosomal subunit protein uS10 5 shared papers
• Ubiquitin carboxyl-terminal hydrolase 10 4 shared papers
• E3 ubiquitin-protein ligase ZNF598 3 shared papers
• Heterogeneous nuclear ribonucleoprotein D0 2 shared papers
• Eukaryotic translation initiation factor 3 subunit C 1 shared papers
• Insulin-like growth factor 2 mRNA-binding protein 1 2 shared papers

Literature · 68 cited papers

• RIOK3 mediates the degradation of 40S ribosomes. Mol. Cell · 2025
• The integrated stress response regulates 18S nonfunctional rRNA decay in mammals. Mol. Cell · 2025
• E3 ubiquitin ligase RNF10 promotes dissociation of stalled ribosomes and responds to ribosomal subunit imbalance. Nat. Commun. · 2024
• iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation. Cell Rep. · 2021
• The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes compromised in translation. Cell Rep. · 2021
• Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized. Elife · 2020
• The G3BP1-family-USP10 deubiquitinase complex rescues ubiquitinated 40S subunits of ribosomes stalled in translation from lysosomal degradation. Mol. Cell · 2020
• Ubiquitination of stalled ribosome triggers ribosome-associated quality control. Nat. Commun. · 2017
• ZNF598 and RACK1 regulate mammalian ribosome-associated quality control function by mediating regulatory 40S ribosomal ubiquitylation. Mol. Cell · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Initiation of quality control during poly(A) translation requires site-specific ribosome ubiquitination. Mol. Cell · 2016
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• … and 56 more in the literature graph