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Identification
HMDB Protein ID HMDBP07407
Secondary Accession Numbers
  • 13094
Name Ribonucleoside-diphosphate reductase subunit M2 B
Synonyms
  1. TP53-inducible ribonucleotide reductase M2 B
  2. p53-inducible ribonucleotide reductase small subunit 2-like protein
  3. p53R2
Gene Name RRM2B
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage.
Pathways
  • Beta Ureidopropionase Deficiency
  • Dihydropyrimidinase Deficiency
  • DNA replication
  • Gemcitabine Action Pathway
  • Gemcitabine Metabolism Pathway
  • Glutathione metabolism
  • MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)
  • p53 signaling pathway
  • Purine Metabolism
  • Purine metabolism
  • Pyrimidine Metabolism
  • Pyrimidine metabolism
  • UMP Synthase Deficiency (Orotic Aciduria)
Reactions
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + Water → ribonucleoside diphosphate + thioredoxin details
dADP + Thioredoxin disulfide + Water → Thioredoxin + ADP details
dGDP + Thioredoxin disulfide + Water → Guanosine diphosphate + Thioredoxin details
dCDP + Thioredoxin disulfide + Water → Thioredoxin + CDP details
2'-Deoxyribonucleoside diphosphate + Tryparedoxin disulfide + Water → Ribonucleoside diphosphate + Tryparedoxin details
2'-Deoxyribonucleoside diphosphate + Trypanothione disulfide + Water → Ribonucleoside diphosphate + Trypanothione details
GO Classification
Biological Process
mitochondrial DNA replication
negative regulation of apoptotic process
nucleobase-containing small molecule interconversion
DNA repair
response to oxidative stress
kidney development
deoxyribonucleotide biosynthetic process
deoxyribonucleoside diphosphate metabolic process
deoxyribonucleoside triphosphate metabolic process
renal system process
Cellular Component
mitochondrion
nucleoplasm
ribonucleoside-diphosphate reductase complex
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
oxidoreductase activity, acting on ch or ch2 groups
oxidoreductase activity, acting on ch or ch2 groups, disulfide as acceptor
ribonucleoside-diphosphate reductase activity
oxidoreductase activity
Molecular Function
transition metal ion binding
ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Process
metabolic process
nitrogen compound metabolic process
cellular nitrogen compound metabolic process
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
nucleobase, nucleoside and nucleotide metabolic process
nucleoside phosphate metabolic process
nucleotide metabolic process
nucleoside diphosphate metabolic process
deoxyribonucleoside diphosphate metabolic process
oxidation reduction
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location 8
Locus 8q23.1
SNPs RRM2B
Gene Sequence
>1056 bp
ATGGGCGACCCGGAAAGGCCGGAAGCGGCCGGGCTGGATCAGGATGAGAGATCATCTTCA
GACACCAACGAAAGTGAAATAAAGTCAAATGAAGAGCCACTCCTAAGAAAGAGTTCTCGC
CGGTTTGTCATCTTTCCAATCCAGTACCCTGATATTTGGAAAATGTATAAACAGGCACAG
GCTTCCTTCTGGACAGCAGAAGAGGTCGACTTATCAAAGGATCTCCCTCACTGGAACAAG
CTTAAAGCAGATGAGAAGTACTTCATCTCTCACATCTTAGCCTTTTTTGCAGCCAGTGAT
GGAATTGTAAATGAAAATTTGGTGGAGCGCTTTAGTCAGGAGGTGCAGGTTCCAGAGGCT
CGCTGTTTCTATGGCTTTCAAATTCTCATCGAGAATGTTCACTCAGAGATGTACAGTTTG
CTGATAGACACTTACATCAGAGATCCCAAGAAAAGGGAATTTTTATTTAATGCAATTGAA
ACCATGCCCTATGTTAAGAAAAAAGCAGATTGGGCCTTGCGATGGATAGCAGATAGAAAA
TCTACTTTTGGGGAAAGAGTGGTGGCCTTTGCTGCTGTAGAAGGAGTTTTCTTCTCAGGA
TCTTTTGCTGCTATATTCTGGCTAAAGAAGAGAGGTCTTATGCCAGGACTCACTTTTTCC
AATGAACTCATCAGCAGAGATGAAGGACTTCACTGTGACTTTGCTTGCCTGATGTTCCAA
TACTTAGTAAATAAGCCTTCAGAAGAAAGGGTCAGGGAGATCATTGTTGATGCTGTCAAA
ATTGAGCAGGAGTTTTTAACAGAAGCCTTGCCAGTTGGCCTCATTGGAATGAATTGCATT
TTGATGAAACAGTACATTGAGTTTGTAGCTGACAGATTACTTGTGGAACTTGGATTCTCA
AAGGTTTTTCAGGCAGAAAATCCTTTTGATTTTATGGAAAACATTTCTTTAGAAGGAAAA
ACAAATTTCTTTGAGAAACGAGTTTCAGAGTATCAGCGTTTTGCAGTTATGGCAGAAACC
ACAGATAACGTCTTCACCTTGGATGCAGATTTTTAA
Protein Properties
Number of Residues 351
Molecular Weight 48786.6
Theoretical pI 7.988
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Ribonucleoside-diphosphate reductase subunit M2 B
MGDPERPEAAGLDQDERSSSDTNESEIKSNEEPLLRKSSRRFVIFPIQYPDIWKMYKQAQ
ASFWTAEEVDLSKDLPHWNKLKADEKYFISHILAFFAASDGIVNENLVERFSQEVQVPEA
RCFYGFQILIENVHSEMYSLLIDTYIRDPKKREFLFNAIETMPYVKKKADWALRWIADRK
STFGERVVAFAAVEGVFFSGSFAAIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFQ
YLVNKPSEERVREIIVDAVKIEQEFLTEALPVGLIGMNCILMKQYIEFVADRLLVELGFS
KVFQAENPFDFMENISLEGKTNFFEKRVSEYQRFAVMAETTDNVFTLDADF
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q7LG56
UniProtKB/Swiss-Prot Entry Name RIR2B_HUMAN
PDB IDs
GenBank Gene ID AB036063
GeneCard ID RRM2B
GenAtlas ID RRM2B
HGNC ID HGNC:17296
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  4. Xue L, Zhou B, Liu X, Qiu W, Jin Z, Yen Y: Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits. Cancer Res. 2003 Mar 1;63(5):980-6. [PubMed:12615712 ]
  5. Qiu W, Zhou B, Darwish D, Shao J, Yen Y: Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Biochem Biophys Res Commun. 2006 Feb 10;340(2):428-34. Epub 2005 Dec 15. [PubMed:16376858 ]
  6. Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y, Nakamura Y: A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature. 2000 Mar 2;404(6773):42-9. [PubMed:10716435 ]
  7. Guittet O, Hakansson P, Voevodskaya N, Fridd S, Graslund A, Arakawa H, Nakamura Y, Thelander L: Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells. J Biol Chem. 2001 Nov 2;276(44):40647-51. Epub 2001 Aug 21. [PubMed:11517226 ]
  8. Yamaguchi T, Matsuda K, Sagiya Y, Iwadate M, Fujino MA, Nakamura Y, Arakawa H: p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Cancer Res. 2001 Nov 15;61(22):8256-62. [PubMed:11719458 ]
  9. Zhou B, Liu X, Mo X, Xue L, Darwish D, Qiu W, Shih J, Hwu EB, Luh F, Yen Y: The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53. Cancer Res. 2003 Oct 15;63(20):6583-94. [PubMed:14583450 ]
  10. Tyynismaa H, Ylikallio E, Patel M, Molnar MJ, Haller RG, Suomalainen A: A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. Am J Hum Genet. 2009 Aug;85(2):290-5. doi: 10.1016/j.ajhg.2009.07.009. Epub 2009 Aug 6. [PubMed:19664747 ]
  11. Smith P, Zhou B, Ho N, Yuan YC, Su L, Tsai SC, Yen Y: 2.6 A X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase . Biochemistry. 2009 Nov 24;48(46):11134-41. doi: 10.1021/bi9001425. [PubMed:19728742 ]
  12. Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, Aubert S, Chretien D, de Lonlay P, Paquis-Flucklinger V, Arakawa H, Nakamura Y, Munnich A, Rotig A: Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet. 2007 Jun;39(6):776-80. Epub 2007 May 7. [PubMed:17486094 ]
  13. Bornstein B, Area E, Flanigan KM, Ganesh J, Jayakar P, Swoboda KJ, Coku J, Naini A, Shanske S, Tanji K, Hirano M, DiMauro S: Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. Neuromuscul Disord. 2008 Jun;18(6):453-9. doi: 10.1016/j.nmd.2008.04.006. Epub 2008 May 27. [PubMed:18504129 ]