UniProt functional annotation for P23396



	UniProt functional annotation for P23396

UniProt code: P23396.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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 during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). 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 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408). {ECO:0000269|PubMed:14706345, ECO:0000269|PubMed:14988002, ECO:0000269|PubMed:15518571, ECO:0000269|PubMed:15707971, ECO:0000269|PubMed:17049931, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:18610840, ECO:0000269|PubMed:18973764, ECO:0000269|PubMed:19656744, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:22510408, ECO:0000269|PubMed:23131551, ECO:0000269|PubMed:23911537, ECO:0000269|PubMed:7775413, ECO:0000269|PubMed:8706699}.

Catalytic activity: Reaction=(DNA)-(deoxyribonucleoside 5'-phosphate)-(deoxyribose 5'- phosphate)-(deoxyribonucleoside 5'-phosphate) = (DNA)-3'- (deoxyribonucleoside 5'-phosphate)-(2,3-dehydro-2,3-deoxyribose 5'- phosphate) + H(+) + phospho-5'-(DNA); Xref=Rhea:RHEA:66592, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695, ChEBI:CHEBI:167181; EC=4.2.99.18; Evidence={ECO:0000269|PubMed:7775413};

Activity regulation: Endonuclease activity is inhibited by MgCl2 on apurinic/apyrimidinic DNA but not on UV-irradiated DNA. {ECO:0000269|PubMed:15707971}.

Biophysicochemical properties: pH dependence: Optimum pH is between 8.0 and 9.0 with activity decreasing sharply below 8.0. {ECO:0000269|PubMed:15707971};

Subunit: Component of the 40S small ribosomal subunit (PubMed:8706699). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with HNRPD (PubMed:24423872). Interacts with PRMT1; the interaction methylates RPS3 (PubMed:19460357). Interacts with SUMO1; the interaction sumoylates RPS3 (PubMed:21968017). Interacts with UBC9 (PubMed:21968017). Interacts with CDK1; the interaction phosphorylates RPS3 (PubMed:21871177). Interacts with PRKCD; the interaction phosphorylates RPS3 (PubMed:19059439). Interacts with PKB/AKT; the interaction phosphorylates RPS3 (PubMed:20605787). Interacts with E2F1; the interaction occurs in the absence of nerve growth factor and increases transcription of pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with the base excision repair proteins APEX1 and OGG1; interaction with OGG1 increases OGG1 N- glycosylase activity (PubMed:15518571). Interacts with UNG; the interaction increases the uracil excision activity of UNG1 (PubMed:18973764). Interacts with HSP90; the interaction prevents the ubiquitination and proteasome-dependent degradation of RPS3 and is suppressed by increased ROS levels (PubMed:16314389). Interacts with TOM70; the interaction promotes translocation of RPS3 to the mitochondrion (PubMed:23911537). Interacts (via N-terminus) with RELA (via N-terminus); the interaction enhances the DNA-binding activity of the NF-kappa-B p65-p50 complex (PubMed:18045535). Interacts with NFKBIA; the interaction is direct and may bridge the interaction between RPS3 and RELA (PubMed:24457201). Interacts with IKKB; the interaction phosphorylates RPS3 and enhances its translocation to the nucleus (PubMed:21399639). Interacts (via KH domain) with MDM2 and TP53 (PubMed:19656744). Interacts with TRADD (PubMed:22510408). Interacts (via N-terminus) with E.coli O157:H7 (strain EDL933) nleH1 and nleH2; the interaction with nleH1 inhibits phosphorylation by IKKB, reduces RPS3 nuclear abundance and inhibits transcriptional activation by the NF-kappa-B p65-p50 complex (PubMed:20041225, PubMed:21399639). Identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon (PubMed:19541769). Interacts with CRY1 (By similarity). {ECO:0000250|UniProtKB:P62908, ECO:0000269|PubMed:15518571, ECO:0000269|PubMed:16314389, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:18973764, ECO:0000269|PubMed:19059439, ECO:0000269|PubMed:19460357, ECO:0000269|PubMed:19541769, ECO:0000269|PubMed:19656744, ECO:0000269|PubMed:20041225, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:21399639, ECO:0000269|PubMed:21871177, ECO:0000269|PubMed:21968017, ECO:0000269|PubMed:22510408, ECO:0000269|PubMed:23911537, ECO:0000269|PubMed:24423872, ECO:0000269|PubMed:24457201, ECO:0000269|PubMed:8706699, ECO:0000303|PubMed:21399639}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:16314389, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:17560175, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:21871177}. Nucleus {ECO:0000269|PubMed:17560175, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:19460357, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:21871177}. Nucleus, nucleolus {ECO:0000269|PubMed:16314389, ECO:0000269|PubMed:19460357}. Mitochondrion inner membrane {ECO:0000269|PubMed:23911537}; Peripheral membrane protein {ECO:0000269|PubMed:23911537}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:23131551}. Note=In normal cells, located mainly in the cytoplasm with small amounts in the nucleus but translocates to the nucleus in cells undergoing apoptosis (By similarity). Nuclear translocation is induced by DNA damaging agents such as hydrogen peroxide (PubMed:17560175). Accumulates in the mitochondrion in response to increased ROS levels (PubMed:23911537). Localizes to the spindle during mitosis (PubMed:23131551). Localized in cytoplasmic mRNP granules containing untranslated mRNAs (PubMed:17289661). {ECO:0000250|UniProtKB:P62908, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:17560175, ECO:0000269|PubMed:23131551, ECO:0000269|PubMed:23911537}.

Ptm: Methylation by PRMT1 is required for import into the nucleolus and for ribosome assembly. {ECO:0000269|PubMed:19460357}.

Ptm: Sumoylation by SUMO1 enhances protein stability through increased resistance to proteolysis. Sumoylation occurs at one or more of the three consensus sites, Lys-18, Lys-214 and Lys-230. {ECO:0000269|PubMed:21968017}.

Ptm: Phosphorylation at Thr-221 by CDK1 occurs mainly in G2/M phase (PubMed:21871177). Phosphorylation by PRKCD occurs on a non-ribosomal- associated form which results in translocation of RPS3 to the nucleus and enhances its endonuclease activity (PubMed:19059439). Phosphorylated on Ser-209 by IKKB in response to activation of the NF- kappa-B p65-p50 complex which enhances the association of RPS3 with importin-alpha and mediates the nuclear translocation of RPS3 (PubMed:21399639). Phosphorylation by MAPK is required for translocation to the nucleus following exposure of cells to DNA damaging agents such as hydrogen peroxide (PubMed:17560175). Phosphorylation by PKB/AKT mediates RPS3 nuclear translocation, enhances RPS3 endonuclease activity and suppresses RPS3-induced neuronal apoptosis (PubMed:20605787). {ECO:0000269|PubMed:17560175, ECO:0000269|PubMed:19059439, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:21399639, ECO:0000269|PubMed:21871177}.

Ptm: Ubiquitinated (PubMed:16314389). This is prevented by interaction with HSP90 which stabilizes the protein (PubMed:16314389). Monoubiquitinated at Lys-214 by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843). {ECO:0000269|PubMed:16314389, ECO:0000269|PubMed:28065601, ECO:0000269|PubMed:28132843}.

Ptm: Ufmylated by UFL1. {ECO:0000250|UniProtKB:P62908}.

Similarity: Belongs to the universal ribosomal protein uS3 family. {ECO:0000305}.

Sequence caution: Sequence=BAB93471.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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 during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). 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 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408). {ECO:0000269\|PubMed:14706345, ECO:0000269\|PubMed:14988002, ECO:0000269\|PubMed:15518571, ECO:0000269\|PubMed:15707971, ECO:0000269\|PubMed:17049931, ECO:0000269\|PubMed:18045535, ECO:0000269\|PubMed:18610840, ECO:0000269\|PubMed:18973764, ECO:0000269\|PubMed:19656744, ECO:0000269\|PubMed:20217897, ECO:0000269\|PubMed:20605787, ECO:0000269\|PubMed:22510408, ECO:0000269\|PubMed:23131551, ECO:0000269\|PubMed:23911537, ECO:0000269\|PubMed:7775413, ECO:0000269\|PubMed:8706699}.


Catalytic activity:		Reaction=(DNA)-(deoxyribonucleoside 5'-phosphate)-(deoxyribose 5'- phosphate)-(deoxyribonucleoside 5'-phosphate) = (DNA)-3'- (deoxyribonucleoside 5'-phosphate)-(2,3-dehydro-2,3-deoxyribose 5'- phosphate) + H(+) + phospho-5'-(DNA); Xref=Rhea:RHEA:66592, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695, ChEBI:CHEBI:167181; EC=4.2.99.18; Evidence={ECO:0000269\|PubMed:7775413};
Activity regulation:		Endonuclease activity is inhibited by MgCl2 on apurinic/apyrimidinic DNA but not on UV-irradiated DNA. {ECO:0000269\|PubMed:15707971}.
Biophysicochemical properties:		pH dependence: Optimum pH is between 8.0 and 9.0 with activity decreasing sharply below 8.0. {ECO:0000269\|PubMed:15707971};
Subunit:		Component of the 40S small ribosomal subunit (PubMed:8706699). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with HNRPD (PubMed:24423872). Interacts with PRMT1; the interaction methylates RPS3 (PubMed:19460357). Interacts with SUMO1; the interaction sumoylates RPS3 (PubMed:21968017). Interacts with UBC9 (PubMed:21968017). Interacts with CDK1; the interaction phosphorylates RPS3 (PubMed:21871177). Interacts with PRKCD; the interaction phosphorylates RPS3 (PubMed:19059439). Interacts with PKB/AKT; the interaction phosphorylates RPS3 (PubMed:20605787). Interacts with E2F1; the interaction occurs in the absence of nerve growth factor and increases transcription of pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with the base excision repair proteins APEX1 and OGG1; interaction with OGG1 increases OGG1 N- glycosylase activity (PubMed:15518571). Interacts with UNG; the interaction increases the uracil excision activity of UNG1 (PubMed:18973764). Interacts with HSP90; the interaction prevents the ubiquitination and proteasome-dependent degradation of RPS3 and is suppressed by increased ROS levels (PubMed:16314389). Interacts with TOM70; the interaction promotes translocation of RPS3 to the mitochondrion (PubMed:23911537). Interacts (via N-terminus) with RELA (via N-terminus); the interaction enhances the DNA-binding activity of the NF-kappa-B p65-p50 complex (PubMed:18045535). Interacts with NFKBIA; the interaction is direct and may bridge the interaction between RPS3 and RELA (PubMed:24457201). Interacts with IKKB; the interaction phosphorylates RPS3 and enhances its translocation to the nucleus (PubMed:21399639). Interacts (via KH domain) with MDM2 and TP53 (PubMed:19656744). Interacts with TRADD (PubMed:22510408). Interacts (via N-terminus) with E.coli O157:H7 (strain EDL933) nleH1 and nleH2; the interaction with nleH1 inhibits phosphorylation by IKKB, reduces RPS3 nuclear abundance and inhibits transcriptional activation by the NF-kappa-B p65-p50 complex (PubMed:20041225, PubMed:21399639). Identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon (PubMed:19541769). Interacts with CRY1 (By similarity). {ECO:0000250\|UniProtKB:P62908, ECO:0000269\|PubMed:15518571, ECO:0000269\|PubMed:16314389, ECO:0000269\|PubMed:17289661, ECO:0000269\|PubMed:18045535, ECO:0000269\|PubMed:18973764, ECO:0000269\|PubMed:19059439, ECO:0000269\|PubMed:19460357, ECO:0000269\|PubMed:19541769, ECO:0000269\|PubMed:19656744, ECO:0000269\|PubMed:20041225, ECO:0000269\|PubMed:20605787, ECO:0000269\|PubMed:21399639, ECO:0000269\|PubMed:21871177, ECO:0000269\|PubMed:21968017, ECO:0000269\|PubMed:22510408, ECO:0000269\|PubMed:23911537, ECO:0000269\|PubMed:24423872, ECO:0000269\|PubMed:24457201, ECO:0000269\|PubMed:8706699, ECO:0000303\|PubMed:21399639}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:16314389, ECO:0000269\|PubMed:17289661, ECO:0000269\|PubMed:17560175, ECO:0000269\|PubMed:18045535, ECO:0000269\|PubMed:20217897, ECO:0000269\|PubMed:21871177}. Nucleus {ECO:0000269\|PubMed:17560175, ECO:0000269\|PubMed:18045535, ECO:0000269\|PubMed:19460357, ECO:0000269\|PubMed:20217897, ECO:0000269\|PubMed:21871177}. Nucleus, nucleolus {ECO:0000269\|PubMed:16314389, ECO:0000269\|PubMed:19460357}. Mitochondrion inner membrane {ECO:0000269\|PubMed:23911537}; Peripheral membrane protein {ECO:0000269\|PubMed:23911537}. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:23131551}. Note=In normal cells, located mainly in the cytoplasm with small amounts in the nucleus but translocates to the nucleus in cells undergoing apoptosis (By similarity). Nuclear translocation is induced by DNA damaging agents such as hydrogen peroxide (PubMed:17560175). Accumulates in the mitochondrion in response to increased ROS levels (PubMed:23911537). Localizes to the spindle during mitosis (PubMed:23131551). Localized in cytoplasmic mRNP granules containing untranslated mRNAs (PubMed:17289661). {ECO:0000250\|UniProtKB:P62908, ECO:0000269\|PubMed:17289661, ECO:0000269\|PubMed:17560175, ECO:0000269\|PubMed:23131551, ECO:0000269\|PubMed:23911537}.
Ptm:		Methylation by PRMT1 is required for import into the nucleolus and for ribosome assembly. {ECO:0000269\|PubMed:19460357}.
Ptm:		Sumoylation by SUMO1 enhances protein stability through increased resistance to proteolysis. Sumoylation occurs at one or more of the three consensus sites, Lys-18, Lys-214 and Lys-230. {ECO:0000269\|PubMed:21968017}.
Ptm:		Phosphorylation at Thr-221 by CDK1 occurs mainly in G2/M phase (PubMed:21871177). Phosphorylation by PRKCD occurs on a non-ribosomal- associated form which results in translocation of RPS3 to the nucleus and enhances its endonuclease activity (PubMed:19059439). Phosphorylated on Ser-209 by IKKB in response to activation of the NF- kappa-B p65-p50 complex which enhances the association of RPS3 with importin-alpha and mediates the nuclear translocation of RPS3 (PubMed:21399639). Phosphorylation by MAPK is required for translocation to the nucleus following exposure of cells to DNA damaging agents such as hydrogen peroxide (PubMed:17560175). Phosphorylation by PKB/AKT mediates RPS3 nuclear translocation, enhances RPS3 endonuclease activity and suppresses RPS3-induced neuronal apoptosis (PubMed:20605787). {ECO:0000269\|PubMed:17560175, ECO:0000269\|PubMed:19059439, ECO:0000269\|PubMed:20605787, ECO:0000269\|PubMed:21399639, ECO:0000269\|PubMed:21871177}.
Ptm:		Ubiquitinated (PubMed:16314389). This is prevented by interaction with HSP90 which stabilizes the protein (PubMed:16314389). Monoubiquitinated at Lys-214 by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843). {ECO:0000269\|PubMed:16314389, ECO:0000269\|PubMed:28065601, ECO:0000269\|PubMed:28132843}.
Ptm:		Ufmylated by UFL1. {ECO:0000250\|UniProtKB:P62908}.
Similarity:		Belongs to the universal ribosomal protein uS3 family. {ECO:0000305}.
Sequence caution:		Sequence=BAB93471.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};