Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009263 deoxyribonucleotide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to deoxyribonucleotide biosynthesis, the canonical process for ribonucleotide reductase small subunits. RRM2B/RRM1 RNR supplies dNTPs via de novo NDP->dNDP reduction. Reason: Core process for RNR small subunits; consistent with direct experimental evidence in this gene and with the IEA/IDA process annotations. Supporting Evidence: PMID:16376858 RR is responsible for the de novo
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation placing RNR activity in the cytosol. Ribonucleotide reduction is a cytosolic process in mammalian cells; the dNTPs produced diffuse to the nucleus or are imported into mitochondria. Reason: Cytosol is the principal, well-supported site of RNR activity for RRM2B (IBA, IDA-HPA, TAS-Reactome all agree). This is the core cellular location. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol
GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the ribonucleoside-diphosphate reductase molecular function. This is the defining catalytic activity of RRM2B as the radical-generating small subunit of the RRM1/RRM2B RNR holoenzyme (EC 1.17.4.1). Reason: Core molecular function, redundantly supported by direct IDA evidence in this gene (PMID:16376858, PMID:12615712), ISS, and IEA (RHEA:23252/EC:1.17.4.1). Supporting Evidence: PMID:16376858 conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates,
GO:0000731 DNA synthesis involved in DNA repair	IDA PMID:11719458 p53R2-dependent pathway for DNA synthesis in a p53-regulated...	ACCEPT	Summary: Direct evidence that p53R2-dependent RNR provides dNTPs for DNA synthesis during repair of damaged DNA in the p53 checkpoint. Inhibition of p53R2 reduced RR activity, DNA repair and survival after genotoxins. Reason: Well-supported specific process for RRM2B's DNA-damage-associated role (supplies dNTPs consumed during repair synthesis). Consistent with the DNA repair BP annotation. Supporting Evidence: PMID:11719458 p53R2-dependent DNA synthesis plays a pivotal role in cell survival by
GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the ribonucleoside-diphosphate reductase function from the mouse ortholog Rrm2b (UniProtKB:Q6PEE3). Same core catalytic activity as the IDA/IBA/IEA annotations. Reason: Duplicate of the core molecular function, transferred by curator from an experimentally characterized ortholog; consistent with direct human evidence. Supporting Evidence: PMID:16376858 conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates,
GO:0005634 nucleus	IDA PMID:11719458 p53R2-dependent pathway for DNA synthesis in a p53-regulated...	ACCEPT	Summary: p53R2 protein accumulated in nuclei after gamma-irradiation. UniProt records nuclear localization with translocation from cytoplasm to nucleus in response to DNA damage. Reason: Directly observed localization. Nucleus is a genuine, DNA-damage-associated location for RRM2B, though later work (PMID:18997010) argues the enzyme is predominantly cytosolic; kept as an observed non-core location. Supporting Evidence: PMID:11719458 The p53R2 product accumulated in nuclei
GO:0005737 cytoplasm	IDA PMID:11719458 p53R2-dependent pathway for DNA synthesis in a p53-regulated...	ACCEPT	Summary: Cytoplasmic localization of p53R2, consistent with the cytosolic site of ribonucleotide reduction and with UniProt (Cytoplasm; Nucleus). Reason: Directly observed location; the more specific cytosol term (GO:0005829) is the core location and is also annotated. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol
GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of the ribonucleoside-diphosphate reductase activity mapped from RHEA:23252 / EC:1.17.4.1, matching the UniProt catalytic activity. Reason: Duplicate of the experimentally supported core molecular function; the EC/RHEA mapping is correct for RRM2B. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt EC=1.17.4.1;
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation to nucleus from the UniProt Subcellular Location vocabulary. Redundant with the IDA nucleus annotation. Reason: Consistent with UniProt-documented nuclear localization (post-DNA-damage translocation); observed non-core location. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Cytoplasm. Nucleus. Note=Translocates from
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation to cytoplasm from the UniProt Subcellular Location vocabulary. Redundant with the IDA cytoplasm annotation. Reason: Consistent with UniProt and with cytosolic ribonucleotide reduction; the more specific cytosol term is the core location. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Cytoplasm. Nucleus. Note=Translocates from
GO:0005739 mitochondrion	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Electronic annotation to mitochondrion, logically inferred from the mitochondrial DNA replication process term (GO:0006264). RRM2B is not documented as a mitochondrial-matrix protein; the enzyme is cytosolic and supplies dNTPs that are imported into mitochondria. Reason: This is an inter-ontology logical inference from the mtDNA-replication process, not physical mitochondrial localization. Direct localization studies place RNR in the cytosol (PMID:18997010); p53R2 supports mtDNA synthesis by supplying cytosolic dNTPs rather than by residing in mitochondria. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol
GO:0006281 DNA repair	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning electronic annotation to DNA repair. RRM2B supplies dNTPs for DNA repair synthesis in the p53 checkpoint. Reason: Consistent with direct experimental evidence (IDA PMID:11719458) and the p53R2 DNA-damage literature; redundant but correct. Supporting Evidence: PMID:11719458 p53R2-dependent DNA synthesis plays a pivotal role in cell survival by
GO:0009185 ribonucleoside diphosphate metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to ribonucleoside diphosphate metabolism, the substrate side of the RNR reaction (NDP -> dNDP). Reason: Correct and consistent with the catalytic activity and with the IDA annotation of the same term (PMID:16376858). Somewhat general but not wrong. Supporting Evidence: PMID:16376858 conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates,
GO:0009263 deoxyribonucleotide biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation to deoxyribonucleotide biosynthesis from the RNR small-subunit domain signatures. Reason: Duplicate of the core IBA process annotation; the InterPro RNR small-chain family mapping is appropriate for RRM2B. Supporting Evidence: PMID:16376858 RR is responsible for the de novo
GO:0009265 2'-deoxyribonucleotide biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to 2'-deoxyribonucleotide biosynthesis, the product side of the RNR reaction. Reason: Correct and supported by direct IDA evidence for the same term (PMID:16376858). Supporting Evidence: PMID:16376858 conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates,
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO electronic annotation to the broad parent term oxidoreductase activity from a general RNR-like domain signature (IPR012348). Reason: Correct but uninformatively general given that the specific child term GO:0004748 (ribonucleoside-diphosphate reductase activity) is already annotated with direct evidence. The specific term should be used. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt EC=1.17.4.1;
GO:1901992 positive regulation of mitotic cell cycle phase transition	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA electronic annotation to positive regulation of a mitotic cell cycle phase transition. RRM2B is a metabolic enzyme; any cell-cycle effect is indirect (dNTP supply / p53 checkpoint) rather than a direct regulatory role. Reason: RRM2B does not directly regulate cell-cycle phase transitions; if anything, p53R2 induction promotes a DNA-damage checkpoint arrest (PMID:10716435), not a positive transition. This ARBA-inferred regulatory term over-interprets the enzyme's metabolic role. Supporting Evidence: PMID:10716435 caused G2/M arrest and prevented cells
GO:0005515 protein binding	IPI PMID:19015526 ATM-mediated serine 72 phosphorylation stabilizes ribonucleo...	MARK AS OVER ANNOTATED	Summary: IntAct-curated protein-binding evidence. In this study p53R2 interacts with ATM and with the ubiquitin ligase MDM2; ATM phosphorylates p53R2 at Ser72 to stabilize it against MDM2-mediated turnover after genotoxic stress. Reason: The bare 'protein binding' term is uninformative and does not capture a molecular function. The underlying interactions (ATM/MDM2) are real and regulatory but are better represented as regulation of protein stability; per curation policy the IPI is retained rather than removed. Supporting Evidence: PMID:19015526 MDM2, a ubiquitin ligase for p53, interacts and
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Protein-binding evidence from a proteome-scale high-throughput yeast two-hybrid interactome map (partner ORC4). Not a specific molecular function. Reason: Bare 'protein binding' from a systematic interactome screen is uninformative about molecular function and is not corroborated by a focused functional study; retained per policy rather than removed. Supporting Evidence: PMID:25416956 we describe a systematic map of ?14,000 high-quality human
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Protein-binding evidence from a large-scale interaction-perturbation study (partner RNF41). Not a specific molecular function. Reason: Bare 'protein binding' from a high-throughput screen; uninformative for molecular function. Retained per policy. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Q7LG56; Q9H4P4: RNF41
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Self-interaction (homotypic) evidence from a proteome-scale interactome map. RNR small subunits adopt a ferritin-like fold and can homodimerize; UniProt lists a Q7LG56-Q7LG56 self-interaction. Reason: Homodimerization is a structural property rather than an informative molecular function for RRM2B (the functional unit is the RRM1/RRM2B heteromeric RNR). Retained per policy. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Q7LG56; Q7LG56: RRM2B
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	MARK AS OVER ANNOTATED	Summary: Self-interaction evidence from a large-scale ORF-clone / variant interaction pipeline. Reason: Homodimerization is a structural feature, not an informative molecular function; retained per policy rather than removed. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Q7LG56; Q7LG56: RRM2B
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Self-interaction evidence from a large-scale study of interaction perturbation by genetic variants. Reason: Homodimerization is structural and uninformative as a molecular function; retained per policy. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Q7LG56; Q7LG56: RRM2B
GO:0006264 mitochondrial DNA replication	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-Compara electronic transfer from the mouse ortholog (Rrm2b, Q6PEE3) of the mitochondrial DNA replication process. p53R2 supplies dNTPs required for mtDNA synthesis in quiescent/post-mitotic cells. Reason: Consistent with the human IMP annotation (PMID:17486094) and with MTDPS8 disease biology; RRM2B provides the deoxyribonucleotide precursors for mtDNA replication. Supporting Evidence: PMID:17486094 in dNTP supply for mtDNA synthesis.
GO:0014075 response to amine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara electronic transfer from a rat ortholog (D4ADQ1) of 'response to amine'. This is a peripheral, non-specific phenotype-derived term not connected to RRM2B's characterized function. Reason: Electronic transfer of a vague stimulus-response term from a rodent ortholog; not supported by any human functional evidence and not part of the gene's core biology. Peripheral over-annotation. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt Belongs to the ribonucleoside diphosphate reductase small
GO:0070318 positive regulation of G0 to G1 transition	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-Compara electronic transfer from the mouse ortholog of 'positive regulation of G0 to G1 transition'. RRM2B/p53R2 supplies dNTPs in resting (G0/G1) cells, but a direct role in driving the G0->G1 transition is not established. Reason: RRM2B is a metabolic enzyme providing dNTPs; any effect on the G0-to-G1 transition is an indirect consequence of precursor supply, not a direct regulatory function. Over-interpreted regulatory term. Supporting Evidence: PMID:11517226 can supply resting cells with deoxyribonucleotides for DNA repair.
GO:0000731 DNA synthesis involved in DNA repair	IDA PMID:12615712 Wild-type p53 regulates human ribonucleotide reductase by pr...	ACCEPT	Summary: Direct evidence that, after UV irradiation, p53R2 and hRRM1 form an active RR complex in the nucleus to provide dNDPs for DNA repair. Reason: Well-supported specific process; duplicate of the IDA from PMID:11719458. RRM2B supplies dNTP precursors for DNA repair synthesis. Supporting Evidence: PMID:12615712 form an active RR complex to provide dNDPs for DNA
GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor	IDA PMID:12615712 Wild-type p53 regulates human ribonucleotide reductase by pr...	ACCEPT	Summary: Direct evidence for reconstituted, active ribonucleotide reductase activity from a p53R2/hRRM1 complex (in vivo RR activity assay tracking nuclear RR subunit accumulation). Reason: Core molecular function, directly demonstrated; consistent with the reconstitution assays of PMID:16376858. Supporting Evidence: PMID:12615712 form an active RR complex to provide dNDPs for DNA
GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor	IDA PMID:16376858 Characterization of enzymatic properties of human ribonucleo...	ACCEPT	Summary: Direct enzymatic characterization of RR holoenzyme reconstituted in vitro from p53R2 + hRRM1; [3H]CDP reduction assay confirmed functional ribonucleotide reductase activity. Reason: Definitive direct evidence for the core catalytic function of RRM2B as the RNR small subunit. Supporting Evidence: PMID:16376858 p53R2 proteins could interact with hRRM1 to form functional RR
GO:0005634 nucleus	IDA PMID:12615712 Wild-type p53 regulates human ribonucleotide reductase by pr...	ACCEPT	Summary: Confocal microscopy showed translocation of p53R2 (with hRRM1 and hRRM2) from cytoplasm to nucleus after UV treatment. Reason: Directly observed nuclear localization after DNA damage; observed non-core location (predominant site of RNR activity is cytosolic, PMID:18997010). Supporting Evidence: PMID:12615712 translocation of hRRM1, p53R2 and hRRM2 from the cytoplasm to the
GO:0005515 protein binding	IPI PMID:12615712 Wild-type p53 regulates human ribonucleotide reductase by pr...	MARK AS OVER ANNOTATED	Summary: Coimmunoprecipitation evidence that p53R2 binds p53/TP53 (UniProtKB:P04637), and that after UV it shifts from binding p53 to binding hRRM1. A functional regulatory interaction, but annotated to the uninformative 'protein binding' term. Reason: The bare 'protein binding' term does not capture a molecular function. The p53R2-TP53 interaction is biologically meaningful (links RNR to the p53 DNA-damage response) but would be better captured as a specific interaction/regulation term; retained per curation policy rather than removed. Supporting Evidence: PMID:12615712 bound to p53 in KB cells, which express wild-type p53.
GO:0005737 cytoplasm	IDA PMID:12615712 Wild-type p53 regulates human ribonucleotide reductase by pr...	ACCEPT	Summary: p53R2 localized to the cytoplasm prior to UV-induced nuclear translocation, consistent with cytosolic ribonucleotide reduction. Reason: Directly observed location; the specific cytosol term is the core location and is separately annotated. Supporting Evidence: PMID:12615712 translocation of hRRM1, p53R2 and hRRM2 from the cytoplasm to the
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence localization to the nucleoplasm. Reason: Consistent with the documented DNA-damage-associated nuclear pool of RRM2B; observed non-core location relative to the predominant cytosolic activity. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt GO:0005654; C:nucleoplasm; IDA:HPA.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence localization to the cytosol, the principal site of ribonucleotide reduction. Reason: Core cellular location, consistent with IBA/TAS and with PMID:18997010. Supporting Evidence: file:human/RRM2B/RRM2B-uniprot.txt GO:0005829; C:cytosol; IDA:HPA.
GO:0000731 DNA synthesis involved in DNA repair	NAS PMID:10716435 A ribonucleotide reductase gene involved in a p53-dependent ...	ACCEPT	Summary: Author statement (from the founding p53R2 paper) that p53R2 encodes a ribonucleotide reductase directly involved in the p53 checkpoint for repair of damaged DNA, supplying nucleotides for DNA repair synthesis. Reason: Consistent with the direct IDA evidence for the same term (PMID:11719458, PMID:12615712); RRM2B provides dNTPs for DNA repair synthesis. Supporting Evidence: PMID:10716435 reductase that is directly involved in the p53 checkpoint for repair of damaged
GO:0005829 cytosol	IDA PMID:18997010 Ribonucleotide reduction is a cytosolic process in mammalian...	ACCEPT	Summary: Three independent localization methods (cytosol/nuclei fractionation, immunofluorescence, fluorescent-tag transfection) showed p53R2 (and R1/R2) reside in the cytosol, arguing against DNA-damage-induced nuclear translocation as a regulatory mechanism. Reason: Strongest direct evidence for the core cytosolic localization of RRM2B/RNR; dNTPs made in the cytosol diffuse to the nucleus or are imported into mitochondria. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol
GO:0006264 mitochondrial DNA replication	IMP PMID:17486094 Mutation of RRM2B, encoding p53-controlled ribonucleotide re...	ACCEPT	Summary: Loss-of-function RRM2B mutations in humans cause severe mtDNA depletion, and the Rrm2b-/- mouse shows severe mtDNA depletion in various tissues, implying p53R2 has a crucial role in dNTP supply for mtDNA synthesis. Reason: Core physiological role established by human mutant phenotype and mouse knockout (MTDPS8). RRM2B does not itself replicate DNA but supplies the deoxyribonucleotide precursors essential for mtDNA replication; this is the disease-defining function. Supporting Evidence: PMID:17486094 in dNTP supply for mtDNA synthesis.
GO:0006281 DNA repair	IDA PMID:11719458 p53R2-dependent pathway for DNA synthesis in a p53-regulated...	ACCEPT	Summary: Inhibition of endogenous p53R2 reduced ribonucleotide reductase activity, DNA repair, and cell survival after exposure to genotoxins, establishing a role in DNA repair. Reason: Directly supported role; RRM2B supplies the dNTP precursors required for DNA repair synthesis in the p53-dependent checkpoint. Supporting Evidence: PMID:11719458 p53R2-dependent DNA synthesis plays a pivotal role in cell survival by
GO:0009185 ribonucleoside diphosphate metabolic process	IDA PMID:16376858 Characterization of enzymatic properties of human ribonucleo...	ACCEPT	Summary: Reconstituted p53R2/hRRM1 RNR catalyzes reduction of ribonucleoside diphosphates, the substrate side of the RNR reaction. Reason: Directly demonstrated; general metabolic-process framing of the RNR reaction, consistent with the more specific biosynthetic terms. Supporting Evidence: PMID:16376858 conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates,
GO:0009265 2'-deoxyribonucleotide biosynthetic process	IDA PMID:16376858 Characterization of enzymatic properties of human ribonucleo...	ACCEPT	Summary: Reconstituted p53R2/hRRM1 RNR produces deoxyribonucleoside diphosphates, the biosynthetic (product) side of the RNR reaction, essential for DNA synthesis and repair. Reason: Directly demonstrated core biosynthetic process for RRM2B; supported by in vitro reconstitution ([3H]CDP reduction). Supporting Evidence: PMID:16376858 which are essential for DNA synthesis and repair.
GO:0010971 positive regulation of G2/M transition of mitotic cell cycle	IDA PMID:10716435 A ribonucleotide reductase gene involved in a p53-dependent ...	MARK AS OVER ANNOTATED	Summary: In the founding paper, induction of p53R2 in p53-deficient cells caused G2/M arrest (a checkpoint), not a positive drive through the G2/M transition. RRM2B is a metabolic enzyme; any cell-cycle effect is indirect. Reason: The cited evidence describes G2/M arrest, which is the opposite direction from 'positive regulation of G2/M transition'. RRM2B does not directly regulate the G2/M transition; this term over-interprets an indirect checkpoint effect. Supporting Evidence: PMID:10716435 caused G2/M arrest and prevented cells
GO:0070318 positive regulation of G0 to G1 transition	IDA PMID:11517226 Mammalian p53R2 protein forms an active ribonucleotide reduc...	MARK AS OVER ANNOTATED	Summary: The cited paper shows an R1-p53R2 complex can supply resting (G0/G1) cells with deoxyribonucleotides for DNA repair; it does not demonstrate that RRM2B positively regulates the G0-to-G1 transition. Reason: RRM2B provides dNTPs in resting cells but a direct role in driving the G0->G1 transition is not established by this evidence; the regulatory term over-interprets the enzyme's metabolic function. Supporting Evidence: PMID:11517226 can supply resting cells with deoxyribonucleotides for DNA repair.
GO:0005829 cytosol	TAS Reactome:R-HSA-111804	ACCEPT	Summary: Reactome traceable-author-statement placing the RNR (M1M2B) NDP->dNDP reaction (thioredoxin) in the cytosol. Reason: Consistent with the core cytosolic localization of RNR (IBA/IDA); redundant but correct. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-5632892	ACCEPT	Summary: Reactome traceable-author-statement (TP53 stimulates transcription of RRM2B) placing RRM2B in the cytosol. Reason: Consistent with the core cytosolic localization; redundant but correct. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-8866405	ACCEPT	Summary: Reactome traceable-author-statement placing the RNR (M1M2B) NDP->dNDP reaction (glutaredoxin) in the cytosol. Reason: Consistent with the core cytosolic localization of RNR; redundant but correct. Supporting Evidence: PMID:18997010 find in all cases that ribonucleotide reductase resides in the cytosol

Core Functions

Radical-generating small subunit of ribonucleotide reductase; with the large catalytic subunit RRM1 it catalyzes the de novo reduction of ribonucleoside diphosphates to 2'-deoxyribonucleoside diphosphates (EC 1.17.4.1) via a diiron-tyrosyl free radical center, using thioredoxin/glutaredoxin as reductant.

Molecular Function:

ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor

Directly Involved In:

deoxyribonucleotide biosynthetic process

Cellular Locations:

cytosol

Supporting Evidence:

PMID:16376858
conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates,

p53/TP53-inducible provider of deoxyribonucleotide precursors for mitochondrial DNA synthesis. In quiescent and post-mitotic cells that lack RRM2, the RRM1/RRM2B complex supplies the dNTPs required for mtDNA replication; loss of RRM2B causes mitochondrial DNA depletion (MTDPS8).

Molecular Function:

ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor

Directly Involved In:

mitochondrial DNA replication

Cellular Locations:

cytosol

Supporting Evidence:

PMID:17486094
in dNTP supply for mtDNA synthesis.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10716435

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage.

PMID:11517226

Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells.

PMID:11719458

p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint.

PMID:12615712

Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits.

PMID:16376858

Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.

PMID:17486094

Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion.

PMID:18997010

Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage.

PMID:19015526

ATM-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53R2 protein against MDM2 to DNA damage.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25502805

A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.

PMID:25910212

Widespread macromolecular interaction perturbations in human genetic disorders.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

Reactome:R-HSA-111804

RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (thioredoxin)

Reactome:R-HSA-5632892

TP53 stimulates transcription of RRM2B gene

Reactome:R-HSA-8866405

RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin)

file:human/RRM2B/RRM2B-uniprot.txt

UniProtKB entry Q7LG56 (RIR2B_HUMAN)

📚 Additional Documentation

Notes

(RRM2B-notes.md)

RRM2B (p53R2) review notes

UniProtKB: Q7LG56 (RIR2B_HUMAN). Gene: RRM2B / P53R2. 351 aa. EC 1.17.4.1.

Core biology (grounded in UniProt + cached PMIDs)

RRM2B encodes the p53-inducible small subunit of ribonucleotide reductase (p53R2).
It is a paralog of the cell-cycle-regulated small subunit RRM2, but unlike RRM2 it is
induced by p53/TP53 in response to DNA damage and is present in resting/quiescent cells
[PMID:10716435, PMID:11517226]. Together with the large catalytic subunit RRM1 it forms an
active ribonucleotide reductase (RNR) that reduces ribonucleoside diphosphates (NDPs) to
2'-deoxyribonucleoside diphosphates (dNDPs) — the rate-limiting de novo step in dNTP supply
for DNA synthesis and repair [PMID:11517226, PMID:16376858].

EC 1.17.4.1 / RHEA:23252: "a 2'-deoxyribonucleoside 5'-diphosphate + [thioredoxin]-disulfide
H2O = a ribonucleoside 5'-diphosphate + [thioredoxin]-dithiol" (UniProt CATALYTIC ACTIVITY).
Cofactor: binds 2 iron ions per subunit; contains a diiron-tyrosyl free radical center
required for catalysis [PMID:19728742 (crystal structure); PMID:11517226 (iron-tyrosyl radical)].
UniProt Fe-binding residues: 100, 131, 134, 194, 228, 231; ACT_SITE 138.

Subcellular location

RNR is a cytosolic process. Pontarin et al. PMID:18997010 used three independent methods
and found R1/R2/p53R2 reside in the cytosol, arguing against the earlier nuclear-translocation
model and supporting a primary function of p53R2 for mtDNA replication. The earlier reports
described translocation cytoplasm->nucleus after DNA damage [PMID:11719458, PMID:12615712];
UniProt SUBCELLULAR LOCATION: "Cytoplasm. Nucleus. Note=Translocates from cytoplasm to nucleus
in response to DNA damage." HPA IDA supports cytosol + nucleoplasm.
Treat cytosol as the core location; nucleus/nucleoplasm/cytoplasm accepted as observed locations.
Mitochondrion IEA (GO_REF:0000108, inferred from GO:0006264) is not a documented physical
localization of the protein — RNR is cytosolic and supplies dNTPs that are imported into
mitochondria; mark over-annotated.

Disease / physiology

MTDPS8A/8B (mitochondrial DNA depletion syndrome 8, encephalomyopathic +/- tubulopathy):
RRM2B mutations cause severe mtDNA depletion; Rrm2b-/- mouse recapitulates this. p53R2 has a
crucial role in dNTP supply for mtDNA synthesis, distinct from DNA repair PMID:17486094.
PEOA5: autosomal dominant progressive external ophthalmoplegia with multiple mtDNA
deletions PMID:19664747.
RCDFRD: rod-cone dystrophy, deafness, Fanconi renal dysfunction PMID:32827185.
These establish the physiological role: providing dNTPs for mitochondrial DNA replication/
synthesis in post-mitotic/quiescent tissues (skeletal muscle high expression).

Annotation review reasoning

MF GO:0004748 (ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
acceptor): CORE. Direct IDA [PMID:16376858 catalytic activity; PMID:12615712], IBA, ISS, IEA
all agree. Accept.
GO:0016491 oxidoreductase activity (IEA, InterPro): correct but far too general given the
specific GO:0004748 is present -> MARK_AS_OVER_ANNOTATED (parent of the specific term).
BP dNTP synthesis: GO:0009263 (deoxyribonucleotide biosynthetic process), GO:0009265
(2'-deoxyribonucleotide biosynthetic process), GO:0009185 (ribonucleoside diphosphate metabolic
process) — all correct core/near-core process terms for RNR. Accept the specific ones; the
ComplexPortal IDA on 0009265 and 0009185 are supported by PMID:16376858. GO:0009185 is somewhat
general (metabolic vs biosynthetic) but correct.
DNA repair GO:0006281 / GO:0000731 (DNA synthesis involved in DNA repair): supported by
IDA PMID:11719458 and the p53-checkpoint literature. Accept as core/near-core (supplies dNTPs
for repair). NAS on 0000731 from PMID:10716435 accepted.
GO:0006264 mitochondrial DNA replication (IMP PMID:17486094; IEA): supported — p53R2 supplies
dNTPs for mtDNA synthesis; loss causes mtDNA depletion. Accept (KEEP_AS_NON_CORE style: it is the
in vivo physiological consequence; RRM2B itself doesn't replicate DNA but supplies precursors).
Keep as core process — this is arguably the most important physiological role.
Cell-cycle regulation terms: GO:1901992 (positive regulation of mitotic cell cycle phase
transition, IEA/ARBA), GO:0010971 (positive regulation of G2/M transition, IDA PMID:10716435),
GO:0070318 (positive regulation of G0 to G1 transition, IDA PMID:11517226 / IEA). PMID:10716435
shows p53R2 induction causes G2/M arrest (a checkpoint), which is not the same as "positive
regulation of G2/M transition". These are indirect/over-interpreted -> MARK_AS_OVER_ANNOTATED.
GO:0070318 IDA is cited to PMID:11517226 which is an in-vitro RNR activity paper about resting
cells; does not directly demonstrate positive regulation of G0->G1 -> MARK_AS_OVER_ANNOTATED.
GO:0014075 response to amine (IEA from rat ortholog, GO_REF:0000107): weakly supported,
electronic transfer from a rat paralog; peripheral -> MARK_AS_OVER_ANNOTATED.
protein binding GO:0005515 (IPI): bare, uninformative. 12615712 = TP53 (functional/regulatory),
19015526 = ATM/MDM2 (regulation of p53R2 stability). Per policy do NOT REMOVE bare protein-binding
IPIs -> MARK_AS_OVER_ANNOTATED (keep the functional context in reason).
identical protein binding GO:0042802 (IPI): RNR small subunits form homodimers (structural
ferritin-like fold; UniProt INTERACTION lists Q7LG56-Q7LG56). Large-scale screens (25416956,
25502805, 31515488). Uninformative for function -> MARK_AS_OVER_ANNOTATED.
Cytosol/cytoplasm/nucleus/nucleoplasm: cytosol (IBA/IDA/TAS/HPA) core; others accepted as
observed locations. Mitochondrion IEA over-annotated (see above).

core_functions (author-supplied, strictly validated)

MF: GO:0004748.
Process: GO:0009263 (deoxyribonucleotide biosynthetic process) — the de novo dNTP supply role.
Process: GO:0006264 (mitochondrial DNA replication) — the key physiological role (dNTP supply
for mtDNA synthesis; disease-defining).
Location: GO:0005829 (cytosol).

QA re-review 2026-07-23 (conservative, no changes)

Independent QA pass over the completed 45-annotation review. Outcome: no edits made —
no problems met the bar for a confident conservative fix.

Checks performed:
- uv run ai-gene-review validate -> ✓ Valid, no warnings.
- protein binding (GO:0005515) x3 IPI and identical protein binding (GO:0042802) x3 IPI
are all MARK_AS_OVER_ANNOTATED (none ACCEPTed), each retained-not-removed per curation
policy with the functional context (TP53, ATM/MDM2, ORC4/RNF41, homodimer) noted in the
reason. Compliant.
- Core function correctly captured and not over-generalized: two core_functions entries both
keyed on MF GO:0004748 (ribonucleoside-diphosphate reductase activity) — (1) de novo dNTP
supply via GO:0009263, (2) dNTP supply for mtDNA replication via GO:0006264 — both located to
cytosol (GO:0005829). MF is in the MF branch, both process ids in BP, location in CC: no
wrong-branch author-supplied ids.
- All PMIDs cited in supporting_text are cached but abstract-only (full_text_available: false);
validation confirms every supporting_text is a verbatim substring of the cached abstract.
- GOA/review completeness: GOA has 46 annotation rows, review has 45. The single delta is a
legitimate WITH/FROM duplicate — GO:0005515 IPI PMID:19015526 has two rows differing only in
partner (MDM2 UniProtKB:Q00987, ATM UniProtKB:Q13315), correctly collapsed to one review
annotation whose summary already names both partners. No annotation is missing.
- Description is clean project-independent biology (no this review/curation/PN framing).

Considered but deliberately left alone (not confident improvements):
- Several non-core observed locations (nucleus, nucleoplasm, cytoplasm) use ACCEPT with reasons
that describe them as "non-core observed location". KEEP_AS_NON_CORE would be marginally more
literal, but ACCEPT-with-note is a consistent, acceptable convention here; not changed.
- Cell-cycle IDA terms (GO:0010971 positive reg G2/M; GO:0070318 positive reg G0->G1) are
MARK_AS_OVER_ANNOTATED with sound arguments (cited papers show G2/M arrest / in-vitro resting
cell dNTP supply, not the annotated positive regulation). A stronger REMOVE is disallowed for
experimental annotations whose full text we have not read; over-annotated is the correct
conservative call. Left as-is.

📄 View Raw YAML

id: Q7LG56
gene_symbol: RRM2B
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: RRM2B (p53R2) is the p53/TP53-inducible small subunit of ribonucleotide
  reductase. Together with the large catalytic subunit RRM1 it forms an active ribonucleotide
  reductase (RNR) that reduces ribonucleoside diphosphates (NDPs) to 2'-deoxyribonucleoside
  diphosphates (dNDPs) via a diiron-tyrosyl free radical center (EC 1.17.4.1), the
  rate-limiting de novo step supplying dNTPs for DNA synthesis and repair. Unlike the
  S-phase/cell-cycle-regulated small subunit RRM2, RRM2B is induced by p53 in response
  to DNA damage and is present in quiescent and post-mitotic cells, where an RRM1/RRM2B
  complex provides dNTPs for DNA repair and, critically, for mitochondrial DNA synthesis.
  Ribonucleotide reduction is a cytosolic process; the deoxyribonucleotides produced
  diffuse to the nucleus or are imported into mitochondria. Loss-of-function mutations
  cause mitochondrial DNA depletion syndrome 8 (MTDPS8, encephalomyopathic form, with
  or without renal tubulopathy) and autosomal-dominant progressive external ophthalmoplegia
  with multiple mtDNA deletions.
alternative_products:
- name: '1'
  id: Q7LG56-1
- name: 2 (Long form)
  id: Q7LG56-2
  sequence_note: VSP_017670
- name: 3 (Short form gamma)
  id: Q7LG56-3
  sequence_note: VSP_017669
- name: 4 (Short form beta)
  id: Q7LG56-4
  sequence_note: VSP_017668
- name: 5 (Short form)
  id: Q7LG56-5
  sequence_note: VSP_017671, VSP_017672
- name: '6'
  id: Q7LG56-6
  sequence_note: VSP_053585
existing_annotations:
- term:
    id: GO:0009263
    label: deoxyribonucleotide biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) annotation to deoxyribonucleotide biosynthesis, the
      canonical process for ribonucleotide reductase small subunits. RRM2B/RRM1 RNR
      supplies dNTPs via de novo NDP->dNDP reduction.
    action: ACCEPT
    reason: Core process for RNR small subunits; consistent with direct experimental
      evidence in this gene and with the IEA/IDA process annotations.
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: RR is responsible for the de novo
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) annotation placing RNR activity in the cytosol. Ribonucleotide
      reduction is a cytosolic process in mammalian cells; the dNTPs produced diffuse
      to the nucleus or are imported into mitochondria.
    action: ACCEPT
    reason: Cytosol is the principal, well-supported site of RNR activity for RRM2B
      (IBA, IDA-HPA, TAS-Reactome all agree). This is the core cellular location.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
- term:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) annotation to the ribonucleoside-diphosphate reductase
      molecular function. This is the defining catalytic activity of RRM2B as the
      radical-generating small subunit of the RRM1/RRM2B RNR holoenzyme (EC 1.17.4.1).
    action: ACCEPT
    reason: Core molecular function, redundantly supported by direct IDA evidence
      in this gene (PMID:16376858, PMID:12615712), ISS, and IEA (RHEA:23252/EC:1.17.4.1).
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: conversion of ribonucleoside diphosphates to deoxyribonucleoside
        diphosphates,
- term:
    id: GO:0000731
    label: DNA synthesis involved in DNA repair
  evidence_type: IDA
  original_reference_id: PMID:11719458
  qualifier: involved_in
  review:
    summary: Direct evidence that p53R2-dependent RNR provides dNTPs for DNA synthesis
      during repair of damaged DNA in the p53 checkpoint. Inhibition of p53R2 reduced
      RR activity, DNA repair and survival after genotoxins.
    action: ACCEPT
    reason: Well-supported specific process for RRM2B's DNA-damage-associated role
      (supplies dNTPs consumed during repair synthesis). Consistent with the DNA
      repair BP annotation.
    supported_by:
    - reference_id: PMID:11719458
      supporting_text: p53R2-dependent DNA synthesis plays a pivotal role in cell
        survival by
- term:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity transfer of the ribonucleoside-diphosphate reductase
      function from the mouse ortholog Rrm2b (UniProtKB:Q6PEE3). Same core catalytic
      activity as the IDA/IBA/IEA annotations.
    action: ACCEPT
    reason: Duplicate of the core molecular function, transferred by curator from
      an experimentally characterized ortholog; consistent with direct human evidence.
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: conversion of ribonucleoside diphosphates to deoxyribonucleoside
        diphosphates,
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11719458
  qualifier: located_in
  review:
    summary: p53R2 protein accumulated in nuclei after gamma-irradiation. UniProt
      records nuclear localization with translocation from cytoplasm to nucleus in
      response to DNA damage.
    action: ACCEPT
    reason: Directly observed localization. Nucleus is a genuine, DNA-damage-associated
      location for RRM2B, though later work (PMID:18997010) argues the enzyme is predominantly
      cytosolic; kept as an observed non-core location.
    supported_by:
    - reference_id: PMID:11719458
      supporting_text: The p53R2 product accumulated in nuclei
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11719458
  qualifier: located_in
  review:
    summary: Cytoplasmic localization of p53R2, consistent with the cytosolic site
      of ribonucleotide reduction and with UniProt (Cytoplasm; Nucleus).
    action: ACCEPT
    reason: Directly observed location; the more specific cytosol term (GO:0005829)
      is the core location and is also annotated.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
- term:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation of the ribonucleoside-diphosphate reductase activity
      mapped from RHEA:23252 / EC:1.17.4.1, matching the UniProt catalytic activity.
    action: ACCEPT
    reason: Duplicate of the experimentally supported core molecular function; the
      EC/RHEA mapping is correct for RRM2B.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'EC=1.17.4.1;'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation to nucleus from the UniProt Subcellular Location
      vocabulary. Redundant with the IDA nucleus annotation.
    action: ACCEPT
    reason: Consistent with UniProt-documented nuclear localization (post-DNA-damage
      translocation); observed non-core location.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: Cytoplasm. Nucleus. Note=Translocates from
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation to cytoplasm from the UniProt Subcellular Location
      vocabulary. Redundant with the IDA cytoplasm annotation.
    action: ACCEPT
    reason: Consistent with UniProt and with cytosolic ribonucleotide reduction; the
      more specific cytosol term is the core location.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: Cytoplasm. Nucleus. Note=Translocates from
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: located_in
  review:
    summary: Electronic annotation to mitochondrion, logically inferred from the mitochondrial
      DNA replication process term (GO:0006264). RRM2B is not documented as a mitochondrial-matrix
      protein; the enzyme is cytosolic and supplies dNTPs that are imported into mitochondria.
    action: MARK_AS_OVER_ANNOTATED
    reason: This is an inter-ontology logical inference from the mtDNA-replication
      process, not physical mitochondrial localization. Direct localization studies
      place RNR in the cytosol (PMID:18997010); p53R2 supports mtDNA synthesis by
      supplying cytosolic dNTPs rather than by residing in mitochondria.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning electronic annotation to DNA repair. RRM2B supplies
      dNTPs for DNA repair synthesis in the p53 checkpoint.
    action: ACCEPT
    reason: Consistent with direct experimental evidence (IDA PMID:11719458) and the
      p53R2 DNA-damage literature; redundant but correct.
    supported_by:
    - reference_id: PMID:11719458
      supporting_text: p53R2-dependent DNA synthesis plays a pivotal role in cell
        survival by
- term:
    id: GO:0009185
    label: ribonucleoside diphosphate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA electronic annotation to ribonucleoside diphosphate metabolism,
      the substrate side of the RNR reaction (NDP -> dNDP).
    action: ACCEPT
    reason: Correct and consistent with the catalytic activity and with the IDA annotation
      of the same term (PMID:16376858). Somewhat general but not wrong.
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: conversion of ribonucleoside diphosphates to deoxyribonucleoside
        diphosphates,
- term:
    id: GO:0009263
    label: deoxyribonucleotide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO electronic annotation to deoxyribonucleotide biosynthesis
      from the RNR small-subunit domain signatures.
    action: ACCEPT
    reason: Duplicate of the core IBA process annotation; the InterPro RNR small-chain
      family mapping is appropriate for RRM2B.
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: RR is responsible for the de novo
- term:
    id: GO:0009265
    label: 2'-deoxyribonucleotide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA electronic annotation to 2'-deoxyribonucleotide biosynthesis, the
      product side of the RNR reaction.
    action: ACCEPT
    reason: Correct and supported by direct IDA evidence for the same term (PMID:16376858).
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: conversion of ribonucleoside diphosphates to deoxyribonucleoside
        diphosphates,
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic annotation to the broad parent term oxidoreductase
      activity from a general RNR-like domain signature (IPR012348).
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct but uninformatively general given that the specific child term
      GO:0004748 (ribonucleoside-diphosphate reductase activity) is already annotated
      with direct evidence. The specific term should be used.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'EC=1.17.4.1;'
- term:
    id: GO:1901992
    label: positive regulation of mitotic cell cycle phase transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA electronic annotation to positive regulation of a mitotic cell cycle
      phase transition. RRM2B is a metabolic enzyme; any cell-cycle effect is indirect
      (dNTP supply / p53 checkpoint) rather than a direct regulatory role.
    action: MARK_AS_OVER_ANNOTATED
    reason: RRM2B does not directly regulate cell-cycle phase transitions; if anything,
      p53R2 induction promotes a DNA-damage checkpoint arrest (PMID:10716435), not
      a positive transition. This ARBA-inferred regulatory term over-interprets the
      enzyme's metabolic role.
    supported_by:
    - reference_id: PMID:10716435
      supporting_text: caused G2/M arrest and prevented cells
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19015526
  qualifier: enables
  review:
    summary: IntAct-curated protein-binding evidence. In this study p53R2 interacts
      with ATM and with the ubiquitin ligase MDM2; ATM phosphorylates p53R2 at Ser72
      to stabilize it against MDM2-mediated turnover after genotoxic stress.
    action: MARK_AS_OVER_ANNOTATED
    reason: 'The bare ''protein binding'' term is uninformative and does not capture
      a molecular function. The underlying interactions (ATM/MDM2) are real and regulatory
      but are better represented as regulation of protein stability; per curation
      policy the IPI is retained rather than removed.'
    supported_by:
    - reference_id: PMID:19015526
      supporting_text: MDM2, a ubiquitin ligase for p53, interacts and
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Protein-binding evidence from a proteome-scale high-throughput yeast
      two-hybrid interactome map (partner ORC4). Not a specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' from a systematic interactome screen is uninformative
      about molecular function and is not corroborated by a focused functional study;
      retained per policy rather than removed.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: we describe a systematic map of ?14,000 high-quality human
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: Protein-binding evidence from a large-scale interaction-perturbation study
      (partner RNF41). Not a specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' from a high-throughput screen; uninformative for
      molecular function. Retained per policy.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'Q7LG56; Q9H4P4: RNF41'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Self-interaction (homotypic) evidence from a proteome-scale interactome
      map. RNR small subunits adopt a ferritin-like fold and can homodimerize; UniProt
      lists a Q7LG56-Q7LG56 self-interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: Homodimerization is a structural property rather than an informative molecular
      function for RRM2B (the functional unit is the RRM1/RRM2B heteromeric RNR).
      Retained per policy.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'Q7LG56; Q7LG56: RRM2B'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  qualifier: enables
  review:
    summary: Self-interaction evidence from a large-scale ORF-clone / variant interaction
      pipeline.
    action: MARK_AS_OVER_ANNOTATED
    reason: Homodimerization is a structural feature, not an informative molecular
      function; retained per policy rather than removed.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'Q7LG56; Q7LG56: RRM2B'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Self-interaction evidence from a large-scale study of interaction perturbation
      by genetic variants.
    action: MARK_AS_OVER_ANNOTATED
    reason: Homodimerization is structural and uninformative as a molecular function;
      retained per policy.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'Q7LG56; Q7LG56: RRM2B'
- term:
    id: GO:0006264
    label: mitochondrial DNA replication
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-Compara electronic transfer from the mouse ortholog (Rrm2b, Q6PEE3)
      of the mitochondrial DNA replication process. p53R2 supplies dNTPs required
      for mtDNA synthesis in quiescent/post-mitotic cells.
    action: ACCEPT
    reason: Consistent with the human IMP annotation (PMID:17486094) and with MTDPS8
      disease biology; RRM2B provides the deoxyribonucleotide precursors for mtDNA
      replication.
    supported_by:
    - reference_id: PMID:17486094
      supporting_text: in dNTP supply for mtDNA synthesis.
- term:
    id: GO:0014075
    label: response to amine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-Compara electronic transfer from a rat ortholog (D4ADQ1) of 'response
      to amine'. This is a peripheral, non-specific phenotype-derived term not connected
      to RRM2B's characterized function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Electronic transfer of a vague stimulus-response term from a rodent ortholog;
      not supported by any human functional evidence and not part of the gene's core
      biology. Peripheral over-annotation.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: Belongs to the ribonucleoside diphosphate reductase small
- term:
    id: GO:0070318
    label: positive regulation of G0 to G1 transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-Compara electronic transfer from the mouse ortholog of 'positive
      regulation of G0 to G1 transition'. RRM2B/p53R2 supplies dNTPs in resting (G0/G1)
      cells, but a direct role in driving the G0->G1 transition is not established.
    action: MARK_AS_OVER_ANNOTATED
    reason: RRM2B is a metabolic enzyme providing dNTPs; any effect on the G0-to-G1
      transition is an indirect consequence of precursor supply, not a direct regulatory
      function. Over-interpreted regulatory term.
    supported_by:
    - reference_id: PMID:11517226
      supporting_text: can supply resting cells with deoxyribonucleotides for DNA
        repair.
- term:
    id: GO:0000731
    label: DNA synthesis involved in DNA repair
  evidence_type: IDA
  original_reference_id: PMID:12615712
  qualifier: involved_in
  review:
    summary: Direct evidence that, after UV irradiation, p53R2 and hRRM1 form an active
      RR complex in the nucleus to provide dNDPs for DNA repair.
    action: ACCEPT
    reason: Well-supported specific process; duplicate of the IDA from PMID:11719458.
      RRM2B supplies dNTP precursors for DNA repair synthesis.
    supported_by:
    - reference_id: PMID:12615712
      supporting_text: form an active RR complex to provide dNDPs for DNA
- term:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  evidence_type: IDA
  original_reference_id: PMID:12615712
  qualifier: enables
  review:
    summary: Direct evidence for reconstituted, active ribonucleotide reductase activity
      from a p53R2/hRRM1 complex (in vivo RR activity assay tracking nuclear RR subunit
      accumulation).
    action: ACCEPT
    reason: Core molecular function, directly demonstrated; consistent with the reconstitution
      assays of PMID:16376858.
    supported_by:
    - reference_id: PMID:12615712
      supporting_text: form an active RR complex to provide dNDPs for DNA
- term:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  evidence_type: IDA
  original_reference_id: PMID:16376858
  qualifier: enables
  review:
    summary: Direct enzymatic characterization of RR holoenzyme reconstituted in vitro
      from p53R2 + hRRM1; [3H]CDP reduction assay confirmed functional ribonucleotide
      reductase activity.
    action: ACCEPT
    reason: Definitive direct evidence for the core catalytic function of RRM2B as
      the RNR small subunit.
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: p53R2 proteins could interact with hRRM1 to form functional
        RR
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12615712
  qualifier: located_in
  review:
    summary: Confocal microscopy showed translocation of p53R2 (with hRRM1 and hRRM2)
      from cytoplasm to nucleus after UV treatment.
    action: ACCEPT
    reason: Directly observed nuclear localization after DNA damage; observed non-core
      location (predominant site of RNR activity is cytosolic, PMID:18997010).
    supported_by:
    - reference_id: PMID:12615712
      supporting_text: translocation of hRRM1, p53R2 and hRRM2 from the cytoplasm
        to the
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12615712
  qualifier: enables
  review:
    summary: Coimmunoprecipitation evidence that p53R2 binds p53/TP53 (UniProtKB:P04637),
      and that after UV it shifts from binding p53 to binding hRRM1. A functional
      regulatory interaction, but annotated to the uninformative 'protein binding'
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The bare 'protein binding' term does not capture a molecular function.
      The p53R2-TP53 interaction is biologically meaningful (links RNR to the p53
      DNA-damage response) but would be better captured as a specific interaction/regulation
      term; retained per curation policy rather than removed.
    supported_by:
    - reference_id: PMID:12615712
      supporting_text: bound to p53 in KB cells, which express wild-type p53.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12615712
  qualifier: located_in
  review:
    summary: p53R2 localized to the cytoplasm prior to UV-induced nuclear translocation,
      consistent with cytosolic ribonucleotide reduction.
    action: ACCEPT
    reason: Directly observed location; the specific cytosol term is the core location
      and is separately annotated.
    supported_by:
    - reference_id: PMID:12615712
      supporting_text: translocation of hRRM1, p53R2 and hRRM2 from the cytoplasm
        to the
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Human Protein Atlas immunofluorescence localization to the nucleoplasm.
    action: ACCEPT
    reason: Consistent with the documented DNA-damage-associated nuclear pool of RRM2B;
      observed non-core location relative to the predominant cytosolic activity.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'GO:0005654; C:nucleoplasm; IDA:HPA.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Human Protein Atlas immunofluorescence localization to the cytosol, the
      principal site of ribonucleotide reduction.
    action: ACCEPT
    reason: Core cellular location, consistent with IBA/TAS and with PMID:18997010.
    supported_by:
    - reference_id: file:human/RRM2B/RRM2B-uniprot.txt
      supporting_text: 'GO:0005829; C:cytosol; IDA:HPA.'
- term:
    id: GO:0000731
    label: DNA synthesis involved in DNA repair
  evidence_type: NAS
  original_reference_id: PMID:10716435
  qualifier: involved_in
  review:
    summary: Author statement (from the founding p53R2 paper) that p53R2 encodes a
      ribonucleotide reductase directly involved in the p53 checkpoint for repair
      of damaged DNA, supplying nucleotides for DNA repair synthesis.
    action: ACCEPT
    reason: Consistent with the direct IDA evidence for the same term (PMID:11719458,
      PMID:12615712); RRM2B provides dNTPs for DNA repair synthesis.
    supported_by:
    - reference_id: PMID:10716435
      supporting_text: reductase that is directly involved in the p53 checkpoint for
        repair of damaged
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:18997010
  qualifier: located_in
  review:
    summary: Three independent localization methods (cytosol/nuclei fractionation,
      immunofluorescence, fluorescent-tag transfection) showed p53R2 (and R1/R2) reside
      in the cytosol, arguing against DNA-damage-induced nuclear translocation as
      a regulatory mechanism.
    action: ACCEPT
    reason: Strongest direct evidence for the core cytosolic localization of RRM2B/RNR;
      dNTPs made in the cytosol diffuse to the nucleus or are imported into mitochondria.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
- term:
    id: GO:0006264
    label: mitochondrial DNA replication
  evidence_type: IMP
  original_reference_id: PMID:17486094
  qualifier: involved_in
  review:
    summary: Loss-of-function RRM2B mutations in humans cause severe mtDNA depletion,
      and the Rrm2b-/- mouse shows severe mtDNA depletion in various tissues, implying
      p53R2 has a crucial role in dNTP supply for mtDNA synthesis.
    action: ACCEPT
    reason: Core physiological role established by human mutant phenotype and mouse
      knockout (MTDPS8). RRM2B does not itself replicate DNA but supplies the deoxyribonucleotide
      precursors essential for mtDNA replication; this is the disease-defining function.
    supported_by:
    - reference_id: PMID:17486094
      supporting_text: in dNTP supply for mtDNA synthesis.
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IDA
  original_reference_id: PMID:11719458
  qualifier: involved_in
  review:
    summary: Inhibition of endogenous p53R2 reduced ribonucleotide reductase activity,
      DNA repair, and cell survival after exposure to genotoxins, establishing a role
      in DNA repair.
    action: ACCEPT
    reason: Directly supported role; RRM2B supplies the dNTP precursors required for
      DNA repair synthesis in the p53-dependent checkpoint.
    supported_by:
    - reference_id: PMID:11719458
      supporting_text: p53R2-dependent DNA synthesis plays a pivotal role in cell
        survival by
- term:
    id: GO:0009185
    label: ribonucleoside diphosphate metabolic process
  evidence_type: IDA
  original_reference_id: PMID:16376858
  qualifier: involved_in
  review:
    summary: Reconstituted p53R2/hRRM1 RNR catalyzes reduction of ribonucleoside diphosphates,
      the substrate side of the RNR reaction.
    action: ACCEPT
    reason: Directly demonstrated; general metabolic-process framing of the RNR reaction,
      consistent with the more specific biosynthetic terms.
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: conversion of ribonucleoside diphosphates to deoxyribonucleoside
        diphosphates,
- term:
    id: GO:0009265
    label: 2'-deoxyribonucleotide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:16376858
  qualifier: involved_in
  review:
    summary: Reconstituted p53R2/hRRM1 RNR produces deoxyribonucleoside diphosphates,
      the biosynthetic (product) side of the RNR reaction, essential for DNA synthesis
      and repair.
    action: ACCEPT
    reason: Directly demonstrated core biosynthetic process for RRM2B; supported by
      in vitro reconstitution ([3H]CDP reduction).
    supported_by:
    - reference_id: PMID:16376858
      supporting_text: which are essential for DNA synthesis and repair.
- term:
    id: GO:0010971
    label: positive regulation of G2/M transition of mitotic cell cycle
  evidence_type: IDA
  original_reference_id: PMID:10716435
  qualifier: involved_in
  review:
    summary: In the founding paper, induction of p53R2 in p53-deficient cells caused
      G2/M arrest (a checkpoint), not a positive drive through the G2/M transition.
      RRM2B is a metabolic enzyme; any cell-cycle effect is indirect.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cited evidence describes G2/M arrest, which is the opposite direction
      from 'positive regulation of G2/M transition'. RRM2B does not directly regulate
      the G2/M transition; this term over-interprets an indirect checkpoint effect.
    supported_by:
    - reference_id: PMID:10716435
      supporting_text: caused G2/M arrest and prevented cells
- term:
    id: GO:0070318
    label: positive regulation of G0 to G1 transition
  evidence_type: IDA
  original_reference_id: PMID:11517226
  qualifier: involved_in
  review:
    summary: The cited paper shows an R1-p53R2 complex can supply resting (G0/G1) cells
      with deoxyribonucleotides for DNA repair; it does not demonstrate that RRM2B
      positively regulates the G0-to-G1 transition.
    action: MARK_AS_OVER_ANNOTATED
    reason: RRM2B provides dNTPs in resting cells but a direct role in driving the
      G0->G1 transition is not established by this evidence; the regulatory term over-interprets
      the enzyme's metabolic function.
    supported_by:
    - reference_id: PMID:11517226
      supporting_text: can supply resting cells with deoxyribonucleotides for DNA
        repair.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-111804
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing the RNR (M1M2B) NDP->dNDP
      reaction (thioredoxin) in the cytosol.
    action: ACCEPT
    reason: Consistent with the core cytosolic localization of RNR (IBA/IDA); redundant
      but correct.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5632892
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement (TP53 stimulates transcription of
      RRM2B) placing RRM2B in the cytosol.
    action: ACCEPT
    reason: Consistent with the core cytosolic localization; redundant but correct.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866405
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing the RNR (M1M2B) NDP->dNDP
      reaction (glutaredoxin) in the cytosol.
    action: ACCEPT
    reason: Consistent with the core cytosolic localization of RNR; redundant but
      correct.
    supported_by:
    - reference_id: PMID:18997010
      supporting_text: find in all cases that ribonucleotide reductase resides in
        the cytosol
core_functions:
- description: Radical-generating small subunit of ribonucleotide reductase; with
    the large catalytic subunit RRM1 it catalyzes the de novo reduction of ribonucleoside
    diphosphates to 2'-deoxyribonucleoside diphosphates (EC 1.17.4.1) via a diiron-tyrosyl
    free radical center, using thioredoxin/glutaredoxin as reductant.
  molecular_function:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  directly_involved_in:
  - id: GO:0009263
    label: deoxyribonucleotide biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:16376858
    supporting_text: conversion of ribonucleoside diphosphates to deoxyribonucleoside
      diphosphates,
- description: p53/TP53-inducible provider of deoxyribonucleotide precursors for mitochondrial
    DNA synthesis. In quiescent and post-mitotic cells that lack RRM2, the RRM1/RRM2B
    complex supplies the dNTPs required for mtDNA replication; loss of RRM2B causes
    mitochondrial DNA depletion (MTDPS8).
  molecular_function:
    id: GO:0004748
    label: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as
      acceptor
  directly_involved_in:
  - id: GO:0006264
    label: mitochondrial DNA replication
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:17486094
    supporting_text: in dNTP supply for mtDNA synthesis.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10716435
  title: A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint
    for DNA damage.
  findings: []
- id: PMID:11517226
  title: Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro
    with the R1 protein, which is expressed both in resting cells in response to DNA
    damage and in proliferating cells.
  findings: []
- id: PMID:11719458
  title: p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint.
  findings: []
- id: PMID:12615712
  title: Wild-type p53 regulates human ribonucleotide reductase by protein-protein
    interaction with p53R2 as well as hRRM2 subunits.
  findings: []
- id: PMID:16376858
  title: Characterization of enzymatic properties of human ribonucleotide reductase
    holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.
  findings: []
- id: PMID:17486094
  title: Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2),
    causes severe mitochondrial DNA depletion.
  findings: []
- id: PMID:18997010
  title: Ribonucleotide reduction is a cytosolic process in mammalian cells independently
    of DNA damage.
  findings: []
- id: PMID:19015526
  title: ATM-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase
    small subunit p53R2 protein against MDM2 to DNA damage.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25502805
  title: A massively parallel pipeline to clone DNA variants and examine molecular
    phenotypes of human disease mutations.
  findings: []
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
- id: Reactome:R-HSA-111804
  title: RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates
    (thioredoxin)
  findings: []
- id: Reactome:R-HSA-5632892
  title: TP53 stimulates transcription of RRM2B gene
  findings: []
- id: Reactome:R-HSA-8866405
  title: RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates
    (glutaredoxin)
  findings: []
- id: file:human/RRM2B/RRM2B-uniprot.txt
  title: UniProtKB entry Q7LG56 (RIR2B_HUMAN)
  findings: []

RRM2B

Gene Description