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FLASH GENE
Symbol RRM2 contributors: mct - updated : 13-07-2017
HGNC name ribonucleotide reductase M2 polypeptide
HGNC id 10452
Location 2p25.1      Physical location : 10.262.694 - 10.271.548
Synonym name
  • ribonucleotide reductase (RnR) M2
    • Synonym symbol(s) R2, RR2, RR2M
    EC.number 1.17.4.1
    DNA
    TYPE functioning gene
    STRUCTURE 8.85 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box) (TATA box)
    text structure TATA box upstream the first initiation site 3 consensus CAAT boxes between the two transcription start sites
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3452 - 449 - 2001 11978970
    10 - 3284 - 389 - 2001 11978970
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Digestiveintestinelarge intestinecolon highly
     intestinesmall intestine  highly
     liver   lowly
     stomach    
    Lymphoid/Immunelymph node    
     spleen    
    Reproductivemale systemtestis  highly
    Respiratorylung   lowly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a Cyclin F-binding motif, in a region of RRM2 located between amino acids 40-65, containing two putative CY motifs
    • HOMOLOGY
    interspecies homolog to murine Rrm2
    Homologene
    FAMILY ribonucleoside diphosphate reductase small chain family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    text
  • is largely cytoplasmic
  • its expression is S phase-specific and required for DNA replication
    • basic FUNCTION
  • ribonucleoside diphosphate reductase activity
  • promoter responsible for cell-cycle specific expression
  • plays an active role in tumor progression
  • its activity is a prosurvival function inactivated by proteolysis during apoptosis
  • plays a significant role in the regulation of cell invasiveness, cell migration and tumor metastasis
    • CELLULAR PROCESS nucleotide, replication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism purine/pyrimidine
    signaling
    pyrimidine biosynthetic pathway
    a component component of the ribonucleotide reductase
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
    binding two iron ions
    protein
  • heterodimerizing with RRM1
  • positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of THBS1 and VEGFA
  • is a new interactor of the F-box protein CCNF
  • Cyclin F directly controls the ubiquitin-mediated degradation of RRM2
  • RRM2 regulates BCL2 protein stability, with RRM2 suppression leading to increased BCL2 degradation, and critical link between RRM2 and BCL2 in apoptosis signaling
  • E2F1 can promote colorectal cancer proliferation, migration, invasion and metastasis by regulating RRM2 transactivation
  • CDKL3 is a promotor for glioma, probably through the regulation of RRM2 and activation of the JNK signalling pathway
    • cell & other
    REGULATION
    Other regulated in a cell cycle dependent manner
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    associated with poor prognosis of gastric cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    RRM2 is a novel target for effective diagnosis and treatment of gastric cancer
    cancerskin 
    inhibition of RRM2 converts the transient response of melanoma cells to BRAF inhibitor to a stable response and may be a novel combinatorial strategy to prolong therapeutic response of melanoma patients
    cancerreproductiveuterus
    inhibition of RRM2 activity may be a novel therapeutic strategy for human cervical cancer
    cancerdigestivecolon
    novel therapeutic target, thus highlighting the potential utility of RRM2 inhibitors in colorectal cancer with oncogenic KRAS
    ANIMAL & CELL MODELS