Ribonucleoside-diphosphate reductase large subunit (RRM1)

The protein contains 792 amino acids for an estimated molecular weight of 90070 Da.

 

Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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VariantDescription
dbSNP:rs2228123
dbSNP:rs2229196

The reference OMIM entry for this protein is 180410

Ribonucleotide reductase, m1 subunit; rrm1
Ribonucleotide reductase, large subunit
Ribonucleotide reductase, r1 subunit; r1

DESCRIPTION

The RRM1 gene encodes the large subunit (R1) of ribonucleotide reductase, the heterodimeric enzyme that catalyzes the rate-limiting step for the production of deoxyribonucleotides needed for DNA synthesis (summary by Pavloff et al., 1992).

CLONING

Pavloff et al. (1992) cloned human RRM1 and RRM2 (180390) cDNAs from a breast carcinoma cDNA library. The deduced 792-amino acid RRM1 protein has a molecular mass of 90 kD and shares about 98% sequence homology with the mouse Rrm1 protein.

MAPPING

By immunoblotting of somatic cell hybrid extracts, Engstrom and Francke (1985) mapped the gene for the R1 subunit of ribonucleotide reductase to 11pter-p11. This assignment was confirmed by Southern analysis of hybrid cell DNAs, and the RRM1 locus was sublocalized to the distal band 11p15 by in situ hybridization (Brissenden et al., 1988). Byrne and Smith (1991) identified a RFLP at the RRM1 locus.

GENE STRUCTURE

Parker et al. (1994) used a fragment of human RRM1 cDNA to isolate a genomic clone that encompassed the 5-prime flanking region of RRM1. Primer extension and PCR experiments defined 6 potential cap sites. Parker et al. (1995) characterized the TATA-less promoter region of the human RRM1 gene and found 2 domains that were conserved with respect to the mouse sequence. One of these sequences was shown to bind the transcription factor SP1 (189906). Pitterle et al. (1999) demonstrated that the RRM1 gene contains 19 exons, spans over 45 kb, and is oriented from telomere to centromere with exon 19 nearest to D11S12.

GENE FUNCTION

In dividing cells, ribonucleotide reductase is essential for the production of deoxyribonucleotides before DNA synthesis in S phase. Neither of its 2 subunits, R1 or R2 (180390), are detectable in quiescent cells. In cycling cells, RRM1 mRNA and protein are present throughout the cell cycle (summary by Parker et al., 1994). Byrne and Smith (1993) found that the RRM1 gene, which is located at 11p15.5, is not imprinted in Wilms tumor or in hepatoblastoma. They demonstrated transcription of both alleles in 6 Wilms tumors, 1 hepatoblastoma, and samples from adjacent kidney and liver from individuals who were constitutionally heterozygous for a TaqI polymorphism. Because the RRM1 gene is located in a region of loss of heterozygosity (LOH) in lung tumors, Pitterle et al. (1999) screened all 19 RRM1 exons in 12 pairs of normal and tumor DNA samples and identified no mutations. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 180410 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed