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RRM2B

Protein FULL name:

ribonucleoside-diphosphate reductase subunit M2 B isoform 1 [Homo sapiens].


RRM2B (Homo sapiens) is product of expression of RRM2B gene.






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.

CATALYTIC ACTIVITY: 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin.

COFACTOR: Binds 2 iron ions per subunit.

PATHWAY: Genetic information processing; DNA replication.

SUBUNIT: Heterotetramer with large (RRM1) subunit. Interacts with p53/TP53. Interacts with RRM1 in response to DNA damage.

SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates from cytoplasm to nucleus in response to DNA damage.

TISSUE SPECIFICITY: Widely expressed at a high level in skeletal muscle and at a weak level in thymus. Expressed in epithelial dysplasias and squamous cell carcinoma.

INDUCTION: In response to DNA damage in a wild-type p53/TP53- dependent manner.

DISEASE: Defects in RRM2B are the cause of encephalomyopathic mitochondrial depletion syndrome with renal tubulopathy (EMDSRT) [MIM:612075]. Mitochondrial DNA depletion syndrome (MDS) is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA (mtDNA) copy number. The encephalomyopathic form with renal tubulopathy is presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis.

DISEASE: Defects in RRM2B are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 5 (PEOA5) [MIM:613077]. A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.

SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small chain family.

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 42544136
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q7LG56 Q7LG56
PFAM: - Q7LG56 (Link - using uniprot id)
InterPro: - Q7LG56 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MGDPERPEAAGLDQDERSSSDTNESEIKSNEEPLLRKSSRRFVIFPIQYP
DIWKMYKQAQASFWTAEEVDLSKDLPHWNKLKADEKYFISHILAFFAASD
GIVNENLVERFSQEVQVPEARCFYGFQILIENVHSEMYSLLIDTYIRDPK
KREFLFNAIETMPYVKKKADWALRWIADRKSTFGERVVAFAAVEGVFFSG
SFAAIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFQYLVNKPSEER
VREIIVDAVKIEQEFLTEALPVGLIGMNCILMKQYIEFVADRLLVELGFS
KVFQAENPFDFMENISLEGKTNFFEKRVSEYQRFAVMAETTDNVFTLDAD
F

RRM2B (Homo sapiens) is able to recognize following damages:
RRM2B (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y, Nakamura Y Nature March 2, 2000
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. Guittet O, Hakansson P, Voevodskaya N, Fridd S, Graslund A, Arakawa H, Nakamura Y, Thelander L J Biol Chem Nov. 2, 2001
p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Yamaguchi T, Matsuda K, Sagiya Y, Iwadate M, Fujino MA, Nakamura Y, Arakawa H Cancer Res Nov. 15, 2001
Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits. Xue L, Zhou B, Liu X, Qiu W, Jin Z, Yen Y Cancer Res March 1, 2003
The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53. Zhou B, Liu X, Mo X, Xue L, Darwish D, Qiu W, Shih J, Hwu EB, Luh F, Yen Y Cancer Res Oct. 15, 2003
Complete sequencing and characterization of 21,243 full-length human cDNAs. 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 Nat Genet Feb. 1, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). 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 Genome Res Oct. 1, 2004
Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Qiu W, Zhou B, Darwish D, Shao J, Yen Y Biochem Biophys Res Commun Jan. 10, 2006
The full-ORF clone resource of the German cDNA Consortium. 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 BMC Genomics Jan. 1, 2007
Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. 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 Nat Genet June 1, 2007
Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. Bornstein B, Area E, Flanigan KM, Ganesh J, Jayakar P, Swoboda KJ, Coku J, Naini A, Shanske S, Tanji K, Hirano M, DiMauro S Neuromuscul Disord June 1, 2008
A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. Tyynismaa H, Ylikallio E, Patel M, Molnar MJ, Haller RG, Suomalainen A Am J Hum Genet Aug. 1, 2009
2.6 A X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase . Smith P, Zhou B, Ho N, Yuan YC, Su L, Tsai SC, Yen Y Biochemistry Nov. 24, 2009


Last modification of this entry: Oct. 11, 2010.

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