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FLASH GENE
Symbol RRM2B contributors: mct - updated : 22-10-2015
HGNC name ribonucleotide reductase M2 B (TP53 inducible)
HGNC id 17296
Corresponding disease
MDDS5 mitochondrial DNA depletion syndrome, encephalomyopathic form
PEO5 progressive external ophthalmoplegia 5
Location 8q22.3      Physical location : 103.216.728 - 103.251.346
Synonym name
  • p53-inducible ribonucleotide reductase small subunit 2 long form
  • p53-inducible ribonucleotide reductase small subunit 2 short form gamma
  • Synonym symbol(s) P53R2, DKFZp686M05248, MGC102856, MGC42116, MTDPS8A, MTDPS8B
    EC.number 1.17.4.1
    DNA
    TYPE functioning gene
    STRUCTURE 34.62 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    COX6C 8q22-q23 cytochrome c oxidase subunit VIc DKFZP434I092 8q22.3 DKFZP434I092 protein LOC286151 8q22.3 similar to RIKEN cDNA 4930533G20 POLR2K 8q22 polymerase (RNA) II (DNA directed) polypeptide K, 7.0kDa SPAG1 8q22 sperm associated antigen 1 RNF19 8q22 ring finger protein 19 LOC157567 8q22.3 hypothetical protein LOC157567 MGC39715 8q22.3 hypothetical protein MGC39715 PABPC1 8q22.2-q23 poly(A) binding protein, cytoplasmic 1 LOC392256 YWHAZ 2p25.2-p25.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide LOC51123 8q22.3 HSPC038 protein FKSG17 8q22.3 HSPC038 protein TFCP2L3 8q22.3 HSPC038 protein NCALD 8q22-q23 neurocalcin delta LOC392257 8 similar to IAP-associated factor VIAF1; phosducin-like 2 RRM2B 8q23.1 ribonucleotide reductase M2 B (TP53 inducible) DD5 8q22 ribonucleotide reductase M2 B (TP53 inducible) ODF1 8q22.3 outer dense fiber of sperm tails 1 TIEG 8q22.2 TGFB inducible early growth response OAZIN 8q22.3 ornithine decarboxylase antizyme inhibitor LOC389679 8 similar to hypothetical protein ATP6V1C1 8q22.3 ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C, isoform 1 LOC389680 8 similar to MGC39526 protein BAALC 8q22.3 brain and acute leukemia, cytoplasmic FZD6 8q22.3-q23.1 frizzled homolog 6 (Drosophila) CTHRC1 8q22.3 collagen triple helix repeat containing 1 MFTC 8q22.3 mitochondrial folate transporter/carrier DKFZP564O0463 8q22.3 DKFZP564O0463 protein TARBP2P 8q22-q24 TAR (HIV) RNA binding protein 2 pseudogene RIMS2 8q22.3 regulating synaptic membrane exocytosis 2 DCSTAMP 8q23 DC-specific transmembrane protein DPYS 8q22 dihydropyrimidinase ST7 7q31.1-q31.3 suppression of tumorigenicity 7 LOC392258 8 similar to ribosomal protein L29
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 4776 - 299 - 2000 10716435
    9 - 4932 40.7 351 - 2000 10716435
    9 - 4913 - 423 - 2000 10716435
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid    
     thyroid    
    Lymphoid/Immunelymph node    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle
    life cycle quiescence
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    intraspecies homolog to RRM2 (80p 100)
    Homologene
    FAMILY
  • ribonucleoside diphosphate reductase small chain family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • is expressed throughout the cell cycle and in quiescent cells where it provides dNTPs for mitochondrial DNA synthesis
  • basic FUNCTION
  • TP53-controled small ribonucleotide reductase, catalyzing the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
  • direct interaction of TP53 with RRM2 and the nuclear accumulation of ribonucleotide reductase subunits after UV exposure might play a pivotal role in DNA repair
  • play essential roles in DNA repair, mtDNA synthesis, and protection against oxidative stress
  • play key roles in forming ribonucleotide reductase holoenzyme and supplying nucleotide precursors for DNA replication and repair
  • may play a key role in defending oxidative stress by scavenging ROS, and this antioxidant property is also important for its enzymatic activity
  • plays critical roles not only in DNA damage repair but also in proliferation of cancer cells
  • required for mitochondrial DNA replication and DNA repair in quiescent cells
  • in postmitotic mammalian cells, RRM2B substitutes for protein R2 as a subunit of ribonucleotide reductase
  • its activity is required for the stability of the mt genome in differentiated tissues, shifting the attention from DNA repair to mtDNA maintenance
  • DNA damage-inducible small subunit of ribonucleotide reductase, the rate-limiting enzyme in de novo deoxyribonucleoside triphosphate synthesis
  • plays a crucial role in maintaining chromosomal stability and preventing chronic-inflammation-associated tumorigenesis
  • its activity is a prosurvival function inactivated by proteolysis during apoptosis
  • critical ribonucleotide reductase (RR) subunit that exists as TP53-inducible and TP53-dependent molecule
  • critical role of RRM2B in mitochondrial homeostasis and the inflammation signaling pathway in a TP53-independent manner
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer of a large (M1) and a small chain (M2)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • binds 2 iron ions per subunit
  • protein
  • interacting with RRM1
  • direct interaction with TP53 and RRM2
  • TP53-inducible ribonucleotide reductase
  • RRM2B as well as its heterodimeric partner RRM1, are associated with ATM
  • MAP2K2 is an endogenous regulator of RRM2B, suggesting that it may associate with RRM2B and upregulate its activity
  • transcriptionally and functionally regulated independent of TP53 pathway by FOXO3
  • role of E2F1 in the regulation of RRM2B expression in DNA damage response (DDR)
  • FOXO3 was identified as a novel regulator of RRM2B
  • cell & other
    REGULATION
    induced by by ultraviolet light in a p53-dependent manner
    by stress signals prior to the onset of senescence and prevents premature oxidative stress-induced senescence
    Other regulated by p53 for supplying nucleotides to repair damaged DNA
    regulation of its activity via ATM-mediated phosphorylation at Ser(72) and MDM2-dependent turnover of RRM2B dephosphorylated at the same residue
    ASSOCIATED DISORDERS
    corresponding disease(s) MDDS5 , PEO5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis, in esophageal squamous cell carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    is a potential target for cancer therapy
    cancer  
    potential target for anticancer drugs as well as a diagnostic marker in cancer
    ANIMAL & CELL MODELS