NameRibonucleoside-diphosphate reductase subunit M2 B
Synonyms
  • 1.17.4.1
  • p53-inducible ribonucleotide reductase small subunit 2-like protein
  • P53R2
  • TP53-inducible ribonucleotide reductase M2 B
Gene NameRRM2B
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006951|Ribonucleoside-diphosphate reductase subunit M2 B
MGDPERPEAAGLDQDERSSSDTNESEIKSNEEPLLRKSSRRFVIFPIQYPDIWKMYKQAQ
ASFWTAEEVDLSKDLPHWNKLKADEKYFISHILAFFAASDGIVNENLVERFSQEVQVPEA
RCFYGFQILIENVHSEMYSLLIDTYIRDPKKREFLFNAIETMPYVKKKADWALRWIADRK
STFGERVVAFAAVEGVFFSGSFAAIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFQ
YLVNKPSEERVREIIVDAVKIEQEFLTEALPVGLIGMNCILMKQYIEFVADRLLVELGFS
KVFQAENPFDFMENISLEGKTNFFEKRVSEYQRFAVMAETTDNVFTLDADF
Number of residues351
Molecular Weight40736.11
Theoretical pI4.61
GO Classification
Functions
  • ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
  • metal ion binding
Processes
  • kidney development
  • nucleobase-containing small molecule metabolic process
  • deoxyribonucleotide biosynthetic process
  • nucleobase-containing small molecule interconversion
  • deoxyribonucleoside diphosphate metabolic process
  • renal system process
  • DNA repair
  • mitochondrial DNA replication
  • deoxyribonucleoside triphosphate metabolic process
  • response to oxidative stress
  • negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator
  • gene expression
  • small molecule metabolic process
  • transcription initiation from RNA polymerase II promoter
Components
  • extracellular exosome
  • nucleoplasm
  • cytoplasm
  • mitochondrion
  • ribonucleoside-diphosphate reductase complex
  • cytosol
General FunctionRibonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific FunctionPlays 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID7229086
UniProtKB IDQ7LG56
UniProtKB Entry NameRIR2B_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021362|Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B)
ATGTTGCTGTTGCGTCTTCCCCCTCACCGCAGTCACGCCAGCCCGTTAGATTGCAAGTTG
CAGGACCGCTGTAGGAAATGTTATTCGCCGCGGTCAGGACAGGCCTGTCCGCCCGCCCTC
GCCGCAGCCTGGCTTCGTCGTTGCGAGCGCCGGGGAGGCCGTCCCCGGGGAGGGCGGAGG
AAGGAGCTGACTTTGGGTTTGCGTCCCGCTCGCTGCTCTGCCCCGGGGCCAGCCAAGGAC
GACGCTTGGAGGCCTCAGGCCGGGAGATCATCTTCAGACACCAACGAAAGTGAAATAAAG
TCAAATGAAGAGCCACTCCTAAGAAAGAGTTCTCGCCGGTTTGTCATCTTTCCAATCCAG
TACCCTGATATTTGGAAAATGTATAAACAGGCACAGGCTTCCTTCTGGACAGCAGAAGAG
GTCGACTTATCAAAGGATCTCCCTCACTGGAACAAGCTTAAAGCAGATGAGAAGTACTTC
ATCTCTCACATCTTAGCCTTTTTTGCAGCCAGTGATGGAATTGTAAATGAAAATTTGGTG
GAGCGCTTTAGTCAGGAGGTGCAGGTTCCAGAGGCTCGCTGTTTCTATGGCTTTCAAATT
CTCATCGAGAATGTTCACTCAGAGATGTACAGTTTGCTGATAGACACTTACATCAGAGAT
CCCAAGAAAAGGGAATTTTTATTTAATGCAATTGAAACCATGCCCTATGTTAAGAAAAAA
GCAGATTGGGCCTTGCGATGGATAGCAGATAGAAAATCTACTTTTGGGGAAAGAGTGGTG
GCCTTTGCTGCTGTAGAAGGAGTTTTCTTCTCAGGATCTTTTGCTGCTATATTCTGGCTA
AAGAAGAGAGGTCTTATGCCAGGACTCACTTTTTCCAATGAACTCATCAGCAGAGATGAA
GGACTTCACTGTGACTTTGCTTGCCTGATGTTCCAATACTTAGTAAATAAGCCTTCAGAA
GAAAGGGTCAGGGAGATCATTGTTGATGCTGTCAAAATTGAGCAGGAGTTTTTAACAGAA
GCCTTGCCAGTTGGCCTCATTGGAATGAATTGCATTTTGATGAAACAGTACATTGAGTTT
GTAGCTGACAGATTACTTGTGGAACTTGGATTCTCAAAGGTTTTTCAGGCAGAAAATCCT
TTTGATTTTATGGAAAACATTTCTTTAGAAGGAAAAACAAATTTCTTTGAGAAACGAGTT
TCAGAGTATCAGCGTTTTGCAGTTATGGCAGAAACCACAGATAACGTCTTCACCTTGGAT
GCAGATTTTTAA
GenBank Gene IDAB036063
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:17296
Chromosome Location8
Locus8q23.1
References
  1. 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. 10716435
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  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. 17974005
  4. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. 16421571
  5. 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. 15489334
  6. 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. 11517226
  7. 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. 11719458
  8. 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. 12615712
  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. 14583450
  10. 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. 16376858
  11. 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. 19664747
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  13. 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. 19728742
  14. 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. 17486094
  15. 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. 18504129
  16. Shaibani A, Shchelochkov OA, Zhang S, Katsonis P, Lichtarge O, Wong LJ, Shinawi M: Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch Neurol. 2009 Aug;66(8):1028-32. doi: 10.1001/archneurol.2009.139. 19667227