RNR4 (CRT3, YGR180C) encodes the second, catalytically inactive small (beta') subunit of the class Ia ribonucleotide reductase of Saccharomyces cerevisiae, a fungal-specific paralog of the radical-bearing Rnr2. Rnr4 lacks three of the conserved iron ligands, binds no iron, and its residual 'radical' tyrosine is dispensable, yet it is essential (or required for normal growth, depending on strain background) because it forms an obligate 1:1 heterodimer with Rnr2 that folds and stabilises Rnr2, allows assembly of the di-iron tyrosyl radical cofactor on Rnr2, and promotes docking of the small subunit onto the Rnr1 (or Rnr3) large subunit. rnr4 null extracts have about 15-fold less radical and very low activity, and RNR2 and RNR4 cannot replace one another. The Rnr2-Rnr4 heterodimer is held in the nucleus by Wtm1 and imported by Dif1 outside S phase and moves to the cytoplasm in S phase or after DNA damage, where it joins the large subunit to reduce ribonucleoside diphosphates to dNDPs. RNR4 transcription is induced by DNA damage through the Mec1-Rad53-Dun1 pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IDA PMID:10535923 Purification of ribonucleotide reductase subunits Y1, Y2, Y3... | ACCEPT | Summary: Nguyen et al.: Y4 is required for assembly of the diiron-tyrosyl radical in Y2; adding Y4 with Fe2+ and O2 activates Y2. contributes_to is the correct qualifier for this non-catalytic subunit. Reason: Core contribution of Rnr4 to RNR activity. Supporting Evidence: PMID:10535923 Y4 appears to play an important role in diiron-Y. assembly of Y2. |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IDA PMID:10716984 Yeast ribonucleotide reductase has a heterodimeric iron-radi... | ACCEPT | Summary: Chabes et al.: Rnr4 folds and stabilises Rnr2 in a 1:1 heterodimer, the only active form of the small subunit. Reason: Core contribution; correct qualifier. Supporting Evidence: PMID:10716984 we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. PMID:10716984 the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:23252/EC 1.17.4.1 mapping applied to the whole R2 family. Rnr4 does not catalyse the reaction itself (no iron, dispensable tyrosine), but is an obligatory component of the active enzyme. Note: Rnr4 is catalytically inactive, so 'contributes_to' is the more accurate qualifier than 'enables'; the term itself is correct. Reason: Term correct for the complex Rnr4 belongs to; qualifier imprecise. Supporting Evidence: PMID:9315671 Rnr4p lacks a number of sequence elements thought to be essential for iron binding, and mutation of the critical tyrosine residue does not affect Rnr4p function. PMID:10716984 the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IGI PMID:9315670 Identification of RNR4, encoding a second essential small su... | ACCEPT | Summary: IGI (Huang and Elledge 1997) with RNR1: rnr4 lethality is suppressed by RNR1 overexpression, consistent with Rnr4 acting in the same enzyme. Note: Rnr4 is catalytically inactive, so 'contributes_to' is the more accurate qualifier than 'enables'; the term itself is correct. Reason: Deferring to curator (abstract-only); supports Rnr4 role in RNR activity. Supporting Evidence: PMID:9315670 The lethality of RNR4 deletion mutations can be suppressed by overexpression of RNR1 and RNR3 |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IGI PMID:9315670 Identification of RNR4, encoding a second essential small su... | ACCEPT | Summary: IGI (Huang and Elledge 1997) with RNR3: RNR3 overexpression also suppresses rnr4 lethality. Note: Rnr4 is catalytically inactive, so 'contributes_to' is the more accurate qualifier than 'enables'; the term itself is correct. Reason: Deferring to curator (abstract-only). Supporting Evidence: PMID:9315670 The lethality of RNR4 deletion mutations can be suppressed by overexpression of RNR1 and RNR3 |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IGI PMID:9315671 Rnr4p, a novel ribonucleotide reductase small-subunit protei... | ACCEPT | Summary: IGI (Wang et al. 1997) with RNR1. Note: Rnr4 is catalytically inactive, so 'contributes_to' is the more accurate qualifier than 'enables'; the term itself is correct. Reason: Deferring to curator (abstract-only); consistent with biochemical evidence. Supporting Evidence: PMID:9315671 These results suggest that Rnr4p is catalytically inactive but, nonetheless, does play a role in the ribonucleotide reductase complex. |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IMP PMID:16285741 The active form of the Saccharomyces cerevisiae ribonucleoti... | ACCEPT | Summary: Perlstein et al. 2005: rnr4-delta extracts have 15-fold less tyrosyl radical and <0.01 vs 0.06 nmol/min/mg activity; beta' is required for cofactor assembly in vivo. Reason: Direct in vivo evidence; correct qualifier. Supporting Evidence: PMID:16285741 The Y* content of rnr4delta is 15-fold less than that of wt PMID:16285741 These studies together demonstrate that beta' plays a crucial role in cluster assembly in vitro and in vivo and that the active form of the yeast R2 is betabeta'. |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | IMP PMID:9315671 Rnr4p, a novel ribonucleotide reductase small-subunit protei... | ACCEPT | Summary: Wang et al. 1997: rnr4 extracts lack RNR activity, restored by adding Rnr4 protein, though Rnr4 is itself catalytically inactive. Note: Rnr4 is catalytically inactive, so 'contributes_to' is the more accurate qualifier than 'enables'; the term itself is correct. Reason: Experimental support for Rnr4 contribution. Supporting Evidence: PMID:9315671 rnr4 mutant extracts are deficient in ribonucleotide reductase activity, and this deficiency can be remedied by the addition of exogenous Rnr4p. PMID:9315671 These results suggest that Rnr4p is catalytically inactive but, nonetheless, does play a role in the ribonucleotide reductase complex. |
| GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-7222-1) with RNR1-4 complexes; contributes_to is correct. Reason: Correct. Supporting Evidence: PMID:10716984 the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit |
| GO:0005515 protein binding | IPI PMID:10716984 Yeast ribonucleotide reductase has a heterodimeric iron-radi... | MODIFY | Summary: IPI Rnr4-Rnr2 (Chabes et al. 2000): stable 1:1 beta-beta' heterodimer. Reason: Replace bare binding with protein heterodimerization activity, the core activity of Rnr4. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:10716984 we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. |
| GO:0005515 protein binding | IPI PMID:10716984 Yeast ribonucleotide reductase has a heterodimeric iron-radi... | REMOVE | Summary: IPI Rnr4-Rnr1 (Chabes et al. 2000): Rnr2/Rnr4 cosediment with Rnr1 as alpha2-beta-beta'. Reason: Bare protein binding to the large subunit; the alpha-beta-beta' association is captured by RNR complex membership and contributes_to RNR activity. Removal does not dispute the interaction. Supporting Evidence: PMID:10716984 In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer |
| GO:0005515 protein binding | IPI PMID:11526233 Structure of the yeast ribonucleotide reductase Y2Y4 heterod... | MODIFY | Summary: IPI Rnr4-Rnr2 from the Y2Y4 heterodimer crystal structure. Reason: Replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:11526233 The heterodimer interface is similar to the mouse R2 homodimer interface in size and interacting residues |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Rnr4-Wtm2 from the Ho et al. 2002 HMS-PCI mass-spectrometry complex screen. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Rnr4-Rnr2 from the Gavin et al. 2006 TAP proteome survey. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:10716984 we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Rnr4-Wtm1 from the Gavin et al. 2006 TAP proteome survey. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005515 protein binding | IPI PMID:16432237 Nuclear localization of the Saccharomyces cerevisiae ribonuc... | MODIFY | Summary: IPI Rnr4-Rnr2 from Zhang et al. 2006 (beta-beta' co-purification with Wtm1/Wtm2). Reason: Replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005515 protein binding | IPI PMID:16432237 Nuclear localization of the Saccharomyces cerevisiae ribonuc... | REMOVE | Summary: IPI Rnr4-Wtm1 from Zhang et al. 2006; Wtm1 is required for nuclear localisation of beta-beta'. Reason: Bare protein binding to the WD40 anchor Wtm1, which retains Rnr2-Rnr4 in the nucleus; the functional consequence is captured by the nucleus localisation annotations. Removal does not dispute the interaction. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. PMID:18851834 We previously reported that Wtm1 anchors Rnr2-Rnr4 in the nucleus. |
| GO:0005515 protein binding | IPI PMID:16537480 Structures of eukaryotic ribonucleotide reductase I define g... | REMOVE | Summary: IPI Rnr4-Rnr1 from Xu et al. 2006 (an Rnr4 C-terminal peptide bound to Rnr1 in a crystal). Reason: Bare protein binding to the large subunit; the alpha-beta-beta' association is captured by RNR complex membership and contributes_to RNR activity. Removal does not dispute the interaction. Supporting Evidence: PMID:16537480 Rnr2, the beta subunit (in yeast, a heterodimer of Rnr2 and Rnr4), houses the diferric-tyrosyl radical crucial for catalysis. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | REMOVE | Summary: Rnr4-Wtm2 from the Yu et al. 2008 binary yeast two-hybrid map. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | REMOVE | Summary: Rnr4-Wtm1 from the Yu et al. 2008 binary yeast two-hybrid map. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005515 protein binding | IPI PMID:21336276 Structural basis for allosteric regulation of human ribonucl... | MODIFY | Summary: IPI Rnr4-Rnr2 from Fairman et al. 2011, which used yeast beta-beta' for holocomplex EM. Reason: Replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:10716984 we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. |
| GO:0005515 protein binding | IPI PMID:21336276 Structural basis for allosteric regulation of human ribonucl... | REMOVE | Summary: IPI Rnr4-Rnr1 from Fairman et al. 2011 (alpha6-beta-beta' holocomplex). Reason: Bare protein binding to the large subunit; the alpha-beta-beta' association is captured by RNR complex membership and contributes_to RNR activity. Removal does not dispute the interaction. Supporting Evidence: PMID:10716984 In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Rnr4-Rnr2 from the Michaelis et al. 2023 proteome-scale interactome. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:10716984 we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Rnr4-Rnr1 from the Michaelis et al. 2023 proteome-scale interactome. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:10716984 In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Rnr4-Wtm2 from the Michaelis et al. 2023 proteome-scale interactome. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Rnr4-Wtm1 from the Michaelis et al. 2023 proteome-scale interactome. Reason: High-throughput interaction screen; bare 'protein binding' carries no functional information. The Rnr2-Rnr4 heterodimer is captured by protein heterodimerization activity, and the Wtm1/Wtm2 association by nuclear localisation of the beta-beta' heterodimer. Supporting Evidence: PMID:16432237 Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with betabeta'. |
| GO:0005634 nucleus | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: Tkach et al. 2012 genome-wide GFP localisation screen (with and without DNA damage) detects Rnr4 in the nucleus, matching small-scale data. Reason: Consistent with IDA evidence. Supporting Evidence: PMID:12732713 Rnr2 and Rnr4 are predominantly present in the nucleus |
| GO:0005634 nucleus | IDA PMID:12732713 Subcellular localization of yeast ribonucleotide reductase r... | ACCEPT | Summary: Yao et al. immunofluorescence: Rnr2 and Rnr4 are predominantly nuclear in unperturbed cells (regulatory storage compartment). Reason: Direct evidence. Supporting Evidence: PMID:12732713 Rnr2 and Rnr4 are predominantly present in the nucleus |
| GO:0005634 nucleus | IDA PMID:9315670 Identification of RNR4, encoding a second essential small su... | ACCEPT | Summary: Huang and Elledge 1997 (abstract-only in cache) localisation data; consistent with later immunofluorescence. Reason: Deferring to curator; consistent with PMID:12732713. Supporting Evidence: PMID:12732713 Rnr2 and Rnr4 are predominantly present in the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping (Nucleus). Correct. Reason: Correct. Supporting Evidence: file:yeast/RNR4/RNR4-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12732713, |
| GO:0005737 cytoplasm | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: Tkach et al. 2012 HT localisation: Rnr4 relocalises to the cytoplasm after DNA damage, as described in small-scale studies. Reason: Consistent with IDA. Supporting Evidence: PMID:12732713 Under genotoxic stress, Rnr2 and Rnr4 become redistributed to the cytoplasm in a checkpoint-dependent manner. |
| GO:0005737 cytoplasm | IDA PMID:12732713 Subcellular localization of yeast ribonucleotide reductase r... | ACCEPT | Summary: Yao et al.: Rnr2/Rnr4 move to the cytoplasm in S phase or after genotoxic stress, where the active holoenzyme forms. Reason: Site of the active enzyme. Supporting Evidence: PMID:12732713 Under genotoxic stress, Rnr2 and Rnr4 become redistributed to the cytoplasm in a checkpoint-dependent manner. |
| GO:0005737 cytoplasm | NAS PMID:16537480 Structures of eukaryotic ribonucleotide reductase I define g... | ACCEPT | Summary: NAS from the Rnr1 structure paper; consistent with IDA. Reason: Consistent. Supporting Evidence: PMID:12732713 Under genotoxic stress, Rnr2 and Rnr4 become redistributed to the cytoplasm in a checkpoint-dependent manner. |
| GO:0005737 cytoplasm | NAS PMID:18851834 Dif1 is a DNA-damage-regulated facilitator of nuclear import... | ACCEPT | Summary: NAS from Lee et al. 2008 (Dif1): Rnr2-Rnr4 enters the cytoplasm to bind Rnr1. Reason: Consistent with IDA. Supporting Evidence: PMID:18851834 In response to S phase or DNA damage, Rnr2-Rnr4 enters the cytoplasm to bind Rnr1, forming an active complex. |
| GO:0005737 cytoplasm | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA places RNR activity in cytoplasm (is_active_in). Correct. Reason: Correct. Supporting Evidence: PMID:18851834 In response to S phase or DNA damage, Rnr2-Rnr4 enters the cytoplasm to bind Rnr1, forming an active complex. |
| GO:0005971 ribonucleoside-diphosphate reductase complex | IDA PMID:10716984 Yeast ribonucleotide reductase has a heterodimeric iron-radi... | ACCEPT | Summary: Chabes et al. 2000: Rnr4 cosediments with Rnr2 and Rnr1 in the holoenzyme. Reason: Core complex membership. Supporting Evidence: PMID:10716984 In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer |
| GO:0005971 ribonucleoside-diphosphate reductase complex | IDA PMID:11526233 Structure of the yeast ribonucleotide reductase Y2Y4 heterod... | ACCEPT | Summary: Voegtli et al. 2001 Y2Y4 heterodimer structure. Reason: Core complex membership. Supporting Evidence: PMID:11526233 The heterodimer interface is similar to the mouse R2 homodimer interface in size and interacting residues |
| GO:0005971 ribonucleoside-diphosphate reductase complex | IPI PMID:10716984 Yeast ribonucleotide reductase has a heterodimeric iron-radi... | ACCEPT | Summary: IPI from Chabes et al. 2000. Reason: Core complex membership. Supporting Evidence: PMID:10716984 In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer |
| GO:0005971 ribonucleoside-diphosphate reductase complex | IPI PMID:9315670 Identification of RNR4, encoding a second essential small su... | ACCEPT | Summary: IPI with RNR2 (SGD:S000003563) from Huang and Elledge 1997 co-immunoprecipitation. Reason: Core complex membership. Supporting Evidence: PMID:9315670 RNR2 and RNR4 may be present in the same reductase complex in vivo, since they coimmunoprecipitate from cell extracts. |
| GO:0009263 deoxyribonucleotide biosynthetic process | IDA PMID:10535923 Purification of ribonucleotide reductase subunits Y1, Y2, Y3... | ACCEPT | Summary: Nguyen et al.: Y4 is needed to generate active Y2. Reason: Core process. Supporting Evidence: PMID:10535923 Y4 appears to play an important role in diiron-Y. assembly of Y2. |
| GO:0009263 deoxyribonucleotide biosynthetic process | IDA PMID:10716984 Yeast ribonucleotide reductase has a heterodimeric iron-radi... | ACCEPT | Summary: Chabes et al.: Rnr2/Rnr4 heterodimer is the active small subunit. Reason: Core process. Supporting Evidence: PMID:10716984 the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit |
| GO:0009263 deoxyribonucleotide biosynthetic process | IDA PMID:5459124 Ribonucleotide reductase from Saccharomyces cerevisiae. | ACCEPT | Summary: Vitols et al. 1970 yeast RNR activity (no abstract cached); process correct for Rnr4 as an obligatory subunit. Reason: Deferring to curator; process supported by PMID:16285741. Supporting Evidence: PMID:16285741 These studies together demonstrate that beta' plays a crucial role in cluster assembly in vitro and in vivo and that the active form of the yeast R2 is betabeta'. |
| GO:0009263 deoxyribonucleotide biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR000358/IPR033909 (RNR small subunit) mapping; correct process for the complex Rnr4 belongs to. Reason: Correct. Supporting Evidence: file:yeast/RNR4/RNR4-uniprot.txt corresponding ribonucleotides. RNR4 is required for proper folding of |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | REMOVE | Summary: InterPro IPR012348 (ferritin-like fold) mapping to oxidoreductase activity. Rnr4 lacks the iron ligands, binds no iron, and its tyrosine is dispensable: it is a pseudo-R2 with no redox chemistry of its own. Reason: Pseudoenzyme over-annotation from fold-level mapping; contradicted by biochemical and structural data. Supporting Evidence: PMID:9315671 Rnr4p lacks a number of sequence elements thought to be essential for iron binding, and mutation of the critical tyrosine residue does not affect Rnr4p function. PMID:10716984 No iron was detected in Rnr4p. PMID:11526233 No metal-binding site is observed in Y4. |
| GO:0046982 protein heterodimerization activity | IDA PMID:11526233 Structure of the yeast ribonucleotide reductase Y2Y4 heterod... | ACCEPT | Summary: Voegtli et al. crystallised the Y2Y4 heterodimer; heterodimerisation with Rnr2 is the molecular basis of Rnr4 function (folding/stabilising Rnr2 for cofactor assembly). Reason: Core activity of Rnr4. Supporting Evidence: PMID:11526233 The heterodimer interface is similar to the mouse R2 homodimer interface in size and interacting residues PMID:10716984 we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. |
| GO:0106387 'de novo' GMP biosynthetic process | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways PWY-7222-1 GO-CAM tags GDP reduction as part_of 'de novo' GMP biosynthesis. RNR produces dGDP and has no role in GMP synthesis. Reason: Pathway-to-GO mapping error; GO:0009263 already annotated. Supporting Evidence: file:yeast/RNR4/RNR4-uniprot.txt corresponding ribonucleotides. RNR4 is required for proper folding of |
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Download this section (compressed HTML)Q: Why did budding yeast (and related fungi) evolve an inactive beta' partner rather than an Rnr2 homodimer, and does Rnr4 confer a regulatory advantage (e.g. nuclear retention or checkpoint control)?
Q: Does Rnr4 contribute residues to the radical transfer pathway or only stabilise Rnr2?
Experiment: Measure radical transfer (PCET) kinetics in Rnr1:Rnr2-Rnr4 with point mutants at the Rnr4 C-terminal docking tail versus the Rnr2 tail, using unnatural-amino-acid radical traps.
Hypothesis: Rnr4 is a structural scaffold without a role in radical transfer
Type: biochemistry / spectroscopy
Ribonucleotide-diphosphate reductase (RNR) small subunit; the RNR complex catalyzes the rate-limiting step in dNTP synthesis and is regulated by DNA replication and DNA damage checkpoint pathways via localization of the small subunits; relocalizes from nucleus to cytoplasm upon DNA replication stress; RNR4 has a paralog, RNR2, that arose from the whole genome duplication
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