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    RRM1 ribonucleotide reductase catalytic subunit M1 [ Homo sapiens (human) ]

    Gene ID: 6240, updated on 28-Oct-2024

    Summary

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    Official Symbol
    RRM1provided by HGNC
    Official Full Name
    ribonucleotide reductase catalytic subunit M1provided by HGNC
    Primary source
    HGNC:HGNC:10451
    See related
    Ensembl:ENSG00000167325 MIM:180410; AllianceGenome:HGNC:10451
    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
    R1; RR1; RIR1; PEOB6
    Summary
    This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
    Expression
    Ubiquitous expression in skin (RPKM 18.5), lymph node (RPKM 18.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RRM1 in Genome Data Viewer
    Location:
    11p15.4
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (4094685..4138932)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (4159950..4204024)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (4115915..4160162)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene stromal interaction molecule 1 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 21 Neighboring gene ribosomal protein S29 pseudogene 20 Neighboring gene Sharpr-MPRA regulatory region 1570 Neighboring gene Sharpr-MPRA regulatory region 9588 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4320 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4321 Neighboring gene olfactory receptor family 55 subfamily B member 1 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:4199970-4200497 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:4200498-4201024 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3094 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:4210694-4210919 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:4214784-4215284 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:4215285-4215785 Neighboring gene long intergenic non-protein coding RNA 2749

    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 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. Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition. Shu Z, et al. Oncogene, 2020 Aug. PMID 32712628
    2. Association of RRM1 -37A>C polymorphism with clinical outcome in colorectal cancer patients treated with gemcitabine-based chemotherapy. Rodriguez J, et al. Eur J Cancer, 2011 Apr. PMID 21220199
    3. Tranilast strongly sensitizes pancreatic cancer cells to gemcitabine via decreasing protein expression of ribonucleotide reductase 1. Mitsuno M, et al. Int J Oncol, 2010 Feb. PMID 20043067
    4. Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells. Kato T, et al. PLoS One, 2021. PMID 34111175, Free PMC Article
    5. A fluorimetric readout reporting the kinetics of nucleotide-induced human ribonucleotide reductase oligomerization. Fu Y, et al. Chembiochem, 2014 Nov 24. PMID 25256246, Free PMC Article

    See all (220) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Prognostic value of RRM1 and its effect on chemoresistance in pancreatic cancer.
      Title: Prognostic value of RRM1 and its effect on chemoresistance in pancreatic cancer.
    2. RRM1 is mediated by histone acetylation through gemcitabine resistance and contributes to invasiveness and ECM remodeling in pancreatic cancer.
      Title: RRM1 is mediated by histone acetylation through gemcitabine resistance and contributes to invasiveness and ECM remodeling in pancreatic cancer.
    3. Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma.
      Title: Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma.
    4. Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells.
      Title: Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells.
    5. Double-staining Immunohistochemistry Reveals in Malignant Pleural Mesothelioma the Coexpression of ERCC1 and RRM1 as a Frequent Biological Event Related to Poorer Survival.
      Title: Double-staining Immunohistochemistry Reveals in Malignant Pleural Mesothelioma the Coexpression of ERCC1 and RRM1 as a Frequent Biological Event Related to Poorer Survival.
    6. Expression patterns and prognostic significances of RRM1 and ERCC1 in pancreatic carcinoma and cholangiocarcinoma.
      Title: Expression patterns and prognostic significances of RRM1 and ERCC1 in pancreatic carcinoma and cholangiocarcinoma.
    7. RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin.
      Title: RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin.
    8. Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells.
      Title: Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells.
    9. LINC02535 co-functions with PCBP2 to regulate DNA damage repair in cervical cancer by stabilizing RRM1 mRNA.
      Title: LINC02535 co-functions with PCBP2 to regulate DNA damage repair in cervical cancer by stabilizing RRM1 mRNA.
    10. Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition.
      Title: Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition.
    Submit: New GeneRIF Correction See all GeneRIFs (113)

    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

    Associated conditions

    Description Tests
    Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6
    MedGen: C5882731 OMIM: 620647 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Expression of HIV-1 Tat upregulates the abundance of ribonucleotide reductase M1 (RRM1) in the nucleoli of Jurkat T-cells 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables disordered domain specific binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ribonucleoside-diphosphate reductase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    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
    		  
    Process Evidence Code Pubs
    involved_in 2'-deoxyribonucleotide biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA synthesis involved in DNA repair NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in cell proliferation in forebrain 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 male gonad development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitochondrial DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of G0 to G1 transition IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of G1/S transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of G2/M 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 pyrimidine nucleobase metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to ionizing radiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in retina development in camera-type eye 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
    located_in cell projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear envelope IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of ribonucleoside-diphosphate reductase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of ribonucleoside-diphosphate reductase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of ribonucleoside-diphosphate reductase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    ribonucleoside-diphosphate reductase large subunit
    Names
    ribonucleoside-diphosphate reductase subunit M1
    ribonucleotide reductase M1 polypeptide
    ribonucleotide reductase, R1 subunit
    NP_001024.1
    NP_001304993.1
    NP_001304994.1
    NP_001317122.1

    NCBI Reference Sequences (RefSeq)

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    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.

    Genomic

    1. NG_027992.2 RefSeqGene

      Range
      5106..49239
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_324

    mRNA and Protein(s)

    1. NM_001033.5 → NP_001024.1  ribonucleoside-diphosphate reductase large subunit isoform 1

      See identical proteins and their annotated locations for NP_001024.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC015689, BC006498, BP229960, BQ775841, CB853003, X59617
      Consensus CDS
      CCDS7750.1
      UniProtKB/Swiss-Prot
      P23921, Q9UNN2
      UniProtKB/TrEMBL
      Q53GZ5
      Related
      ENSP00000300738.5, ENST00000300738.10
      Conserved Domains (1) summary
      PLN02437
      Location:1 → 792
      PLN02437; ribonucleoside--diphosphate reductase large subunit

    2. NM_001318064.1 → NP_001304993.1  ribonucleoside-diphosphate reductase large subunit isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream translation start site compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC015689, AK303394, BP229960, BQ775841, CB853003, X59617
      UniProtKB/TrEMBL
      B4E0I8
      Conserved Domains (2) summary
      cd01679
      Location:70 → 644
      RNR_I; Class I ribonucleotide reductase
      pfam02867
      Location:119 → 641
      Ribonuc_red_lgC; Ribonucleotide reductase, barrel domain

    3. NM_001318065.1 → NP_001304994.1  ribonucleoside-diphosphate reductase large subunit isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, and uses a downstream translation start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC015689, AK301922, AK311593, BC006498, BQ775841, CB853003
      UniProtKB/TrEMBL
      B4DXD1
      Conserved Domains (1) summary
      cl38938
      Location:1 → 454
      RNR_PFL; Ribonucleotide reductase and Pyruvate formate lyase

    4. NM_001330193.1 → NP_001317122.1  ribonucleoside-diphosphate reductase large subunit isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (4) has a shorter N-terminus than isoform 1.
      Source sequence(s)
      AC015689, AK311593, BF681281, BM464333
      Consensus CDS
      CCDS81547.1
      UniProtKB/TrEMBL
      B4DXB0, E9PL69
      Related
      ENSP00000431464.1, ENST00000534285.5
      Conserved Domains (2) summary
      cd01679
      Location:3 → 519
      RNR_I; Class I ribonucleotide reductase
      pfam02867
      Location:1 → 516
      Ribonuc_red_lgC; Ribonucleotide reductase, barrel domain

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      4094685..4138932
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      4159950..4204024
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P23921.1 GenPept UniProtKB/Swiss-Prot:P23921

    Gene LinkOut

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

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