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    RRM2 ribonucleotide reductase regulatory subunit M2 [ Homo sapiens (human) ]

    Gene ID: 6241, updated on 10-Dec-2024

    Summary

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    Official Symbol
    RRM2provided by HGNC
    Official Full Name
    ribonucleotide reductase regulatory subunit M2provided by HGNC
    Primary source
    HGNC:HGNC:10452
    See related
    Ensembl:ENSG00000171848 MIM:180390; AllianceGenome:HGNC:10452
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    R2; RR2; RR2M; C2orf48
    Summary
    This gene encodes one of two non-identical subunits for ribonucleotide reductase. This reductase catalyzes the formation of deoxyribonucleotides from ribonucleotides. Synthesis of the encoded protein (M2) is regulated in a cell-cycle dependent fashion. Transcription from this gene can initiate from alternative promoters, which results in two isoforms that differ in the lengths of their N-termini. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Sep 2009]
    Expression
    Biased expression in bone marrow (RPKM 28.1), lymph node (RPKM 20.5) and 13 other tissues See more
    Orthologs
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    Genomic context

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    See RRM2 in Genome Data Viewer
    Location:
    2p25.1
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (10122568..10211010)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (10151280..10239549)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (10262695..10351136)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:10197717-10198660 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:10198661-10199603 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10200462-10201324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10201325-10202185 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10203342-10203940 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10203941-10204538 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10204790-10205668 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10205669-10206546 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10211417-10211918 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11154 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11155 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11156 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11157 Neighboring gene cystin 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15296 Neighboring gene uncharacterized LOC124900536 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:10231300-10231817 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15297 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:10259653-10260596 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:10260597-10261539 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:10261588-10262143 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:10262327-10262827 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr2:10273128-10273791 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11159 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10282796-10283457 Neighboring gene small nucleolar RNA SNORA2/SNORA34 family Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10303055-10303660 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10303661-10304265 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10309414-10310044 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10311305-10311934 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10311935-10312564 Neighboring gene uncharacterized LOC105373424 Neighboring gene microRNA 4261 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10357075-10357867 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10366095-10366704 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:10393383-10394004 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10395247-10395866 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:10411801-10412301 Neighboring gene uncharacterized LOC124907731 Neighboring gene RNA, 7SL, cytoplasmic 66, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Differential processing of let-7a precursors influences RRM2 expression and chemosensitivity in pancreatic cancer: role of LIN-28 and SET oncoprotein. Bhutia YD, et al. PLoS One, 2013. PMID 23335963, Free PMC Article
    2. Novel human-derived EML4-ALK fusion cell lines identify ribonucleotide reductase RRM2 as a target of activated ALK in NSCLC. Bokhari AA, et al. Lung Cancer, 2022 Sep. PMID 35933914
    3. Stable suppression of the R2 subunit of ribonucleotide reductase by R2-targeted short interference RNA sensitizes p53(-/-) HCT-116 colon cancer cells to DNA-damaging agents and ribonucleotide reductase inhibitors. Lin ZP, et al. J Biol Chem, 2004 Jun 25. PMID 15096505
    4. Tumor suppressive activity of PIWI-interacting RNA in human fibrosarcoma mediated through repression of RRM2. Das B, et al. Mol Carcinog, 2019 Mar. PMID 30362638
    5. Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer. Morikawa T, et al. Histopathology, 2010 Dec. PMID 21166702

    See all (208) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RRM2 Is a CTNNB1 Transport Regulator Promoting Colon Cancer Progression.
      Title: RRM2 Is a CTNNB1 Transport Regulator Promoting Colon Cancer Progression.
    2. IGF2BP3 regulates the expression of RRM2 and promotes the progression of rheumatoid arthritis via RRM2/Akt/MMP-9 pathway.
      Title: IGF2BP3 regulates the expression of RRM2 and promotes the progression of rheumatoid arthritis via RRM2/Akt/MMP-9 pathway.
    3. A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer.
      Title: A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer.
    4. Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.
      Title: Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.
    5. E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma.
      Title: E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma.
    6. Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients.
      Title: Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients.
    7. USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2.
      Title: USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2.
    8. Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production.
      Title: Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production.
    9. MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells.
      Title: MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells.
    10. Ribonucleotide reductase subunit switching in hepatoblastoma drug response and relapse.
      Title: Ribonucleotide reductase subunit switching in hepatoblastoma drug response and relapse.
    Submit: New GeneRIF Correction See all GeneRIFs (129)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Pol gag-pol HIV-1 Pol is identified to have a physical interaction with ribonucleotide reductase M2 (RRM2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ25102, MGC121034, MGC121036

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ferric iron binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in 2'-deoxyribonucleotide biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in blastocyst development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in deoxyribonucleotide biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in deoxyribonucleotide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of G1/S transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein heterotetramerization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ribonucleoside diphosphate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of ribonucleoside-diphosphate reductase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ribonucleoside-diphosphate reductase subunit M2
    Names
    ribonucleotide reductase M2 polypeptide
    ribonucleotide reductase small chain
    ribonucleotide reductase small subunit
    uncharacterized protein C2orf48
    NP_001025.1
    NP_001159403.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001034.4 → NP_001025.1  ribonucleoside-diphosphate reductase subunit M2 isoform 2

      See identical proteins and their annotated locations for NP_001025.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternative downstream promoter, and it thus has a shorter 5' UTR and uses a downstream translational start codon, compared to variant 1. The encoded isoform (2) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AC104794, AC118058, BM994533, X59618
      Consensus CDS
      CCDS1669.1
      UniProtKB/Swiss-Prot
      B2R9B5, J3KP43, P31350, Q5WRU7
      UniProtKB/TrEMBL
      A0A286YFD6
      Related
      ENSP00000302955.4, ENST00000304567.10
      Conserved Domains (1) summary
      PLN02492
      Location:70 → 389
      PLN02492; ribonucleoside-diphosphate reductase

    2. NM_001165931.1 → NP_001159403.1  ribonucleoside-diphosphate reductase subunit M2 isoform 1

      See identical proteins and their annotated locations for NP_001159403.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC104794, AC118058, BM994533, DA477511, X59618
      Consensus CDS
      CCDS54334.1
      Related
      ENSP00000353770.2, ENST00000360566.6
      Conserved Domains (1) summary
      PLN02492
      Location:130 → 449
      PLN02492; ribonucleoside-diphosphate reductase

    RNA

    1. NR_164157.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC007240, AC104794

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      10122568..10211010
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      10151280..10239549
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_161344.1: Suppressed sequence

      Description
      NR_161344.1: This RefSeq was removed because currently there is insufficient support for the transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P31350.1 GenPept UniProtKB/Swiss-Prot:P31350
    Q96LS8.1 GenPept UniProtKB/Swiss-Prot:Q96LS8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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