ID RIR2B_HUMAN Reviewed; 351 AA. AC Q7LG56; B4E2N4; Q17R22; Q75PQ6; Q75PQ7; Q75PY8; Q75PY9; Q86YE3; Q9NPD6; AC Q9NTD8; Q9NUW3; DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 189. DE RecName: Full=Ribonucleoside-diphosphate reductase subunit M2 B; DE EC=1.17.4.1; DE AltName: Full=TP53-inducible ribonucleotide reductase M2 B; DE AltName: Full=p53-inducible ribonucleotide reductase small subunit 2-like protein; DE Short=p53R2; GN Name=RRM2B; Synonyms=P53R2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, AND RP INDUCTION. RX PubMed=10716435; DOI=10.1038/35003506; RA Tanaka H., Arakawa H., Yamaguchi T., Shiraishi K., Fukuda S., Matsui K., RA Takei Y., Nakamura Y.; RT "A ribonucleotide reductase gene involved in a p53-dependent cell-cycle RT checkpoint for DNA damage."; RL Nature 404:42-49(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5). RA Ugai H., Yokoyama K.K.; RT "Homo sapiens p53-inducible ribonucleotide reductase small subunit 2 RT splicing variants."; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-351 (ISOFORM 6). RC TISSUE=Placenta, and Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Amygdala; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP FUNCTION, AND SUBUNIT. RX PubMed=11517226; DOI=10.1074/jbc.m106088200; RA Guittet O., Haakansson P., Voevodskaya N., Fridd S., Graeslund A., RA Arakawa H., Nakamura Y., Thelander L.; RT "Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro RT with the R1 protein, which is expressed both in resting cells in response RT to DNA damage and in proliferating cells."; RL J. Biol. Chem. 276:40647-40651(2001). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND VARIANT LEU-115. RX PubMed=11719458; RA Yamaguchi T., Matsuda K., Sagiya Y., Iwadate M., Fujino M.A., Nakamura Y., RA Arakawa H.; RT "p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle RT checkpoint."; RL Cancer Res. 61:8256-8262(2001). RN [11] RP SUBCELLULAR LOCATION, AND INTERACTION WITH TP53 AND RRM1. RX PubMed=12615712; RA Xue L., Zhou B., Liu X., Qiu W., Jin Z., Yen Y.; RT "Wild-type p53 regulates human ribonucleotide reductase by protein-protein RT interaction with p53R2 as well as hRRM2 subunits."; RL Cancer Res. 63:980-986(2003). RN [12] RP TISSUE SPECIFICITY. RX PubMed=14583450; RA Zhou B., Liu X., Mo X., Xue L., Darwish D., Qiu W., Shih J., Hwu E.B., RA Luh F., Yen Y.; RT "The human ribonucleotide reductase subunit hRRM2 complements p53R2 in RT response to UV-induced DNA repair in cells with mutant p53."; RL Cancer Res. 63:6583-6594(2003). RN [13] RP CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=16376858; DOI=10.1016/j.bbrc.2005.12.019; RA Qiu W., Zhou B., Darwish D., Shao J., Yen Y.; RT "Characterization of enzymatic properties of human ribonucleotide reductase RT holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits."; RL Biochem. Biophys. Res. Commun. 340:428-434(2006). RN [14] RP INVOLVEMENT IN PEOA5. RX PubMed=19664747; DOI=10.1016/j.ajhg.2009.07.009; RA Tyynismaa H., Ylikallio E., Patel M., Molnar M.J., Haller R.G., RA Suomalainen A.; RT "A heterozygous truncating mutation in RRM2B causes autosomal-dominant RT progressive external ophthalmoplegia with multiple mtDNA deletions."; RL Am. J. Hum. Genet. 85:290-295(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH IRON IONS, AND RP COFACTOR. RX PubMed=19728742; DOI=10.1021/bi9001425; RA Smith P., Zhou B., Ho N., Yuan Y.C., Su L., Tsai S.C., Yen Y.; RT "2.6 A X-ray crystal structure of human p53R2, a p53-inducible RT ribonucleotide reductase."; RL Biochemistry 48:11134-11141(2009). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 20-322 IN COMPLEX WITH IRON IONS. RG Structural genomics consortium (SGC); RT "Human ribonucleotide reductase, subunit M2 B."; RL Submitted (FEB-2009) to the PDB data bank. RN [18] RP VARIANTS MTDPS8A ARG-64; GLU-85 DEL; GLY-194; LYS-194 AND PHE-236. RX PubMed=17486094; DOI=10.1038/ng2040; RA Bourdon A., Minai L., Serre V., Jais J.-P., Sarzi E., Aubert S., RA Chretien D., de Lonlay P., Paquis-Flucklinger V., Arakawa H., Nakamura Y., RA Munnich A., Roetig A.; RT "Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase RT (p53R2), causes severe mitochondrial DNA depletion."; RL Nat. Genet. 39:776-780(2007). RN [19] RP VARIANTS MTDPS8A SER-224; ILE-282 AND VAL-317. RX PubMed=18504129; DOI=10.1016/j.nmd.2008.04.006; RA Bornstein B., Area E., Flanigan K.M., Ganesh J., Jayakar P., Swoboda K.J., RA Coku J., Naini A., Shanske S., Tanji K., Hirano M., DiMauro S.; RT "Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene."; RL Neuromuscul. Disord. 18:453-459(2008). RN [20] RP VARIANTS MTDPS8B HIS-110 AND HIS-121. RX PubMed=19667227; DOI=10.1001/archneurol.2009.139; RA Shaibani A., Shchelochkov O.A., Zhang S., Katsonis P., Lichtarge O., RA Wong L.J., Shinawi M.; RT "Mitochondrial neurogastrointestinal encephalopathy due to mutations in RT RRM2B."; RL Arch. Neurol. 66:1028-1032(2009). RN [21] RP VARIANT SER-33. RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679; RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y., RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H., RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y., RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K., RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M., RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K., RA Ohtake A., Okazaki Y.; RT "A comprehensive genomic analysis reveals the genetic landscape of RT mitochondrial respiratory chain complex deficiencies."; RL PLoS Genet. 12:E1005679-E1005679(2016). RN [22] RP VARIANT RCDFRD ASP-262, AND INVOLVEMENT IN RCDFRD. RX PubMed=32827185; DOI=10.1002/humu.24094; RA Roberts L., Julius S., Dawlat S., Yildiz S., Rebello G., Meldau S., RA Pillay K., Esterhuizen A., Vorster A., Benefeld G., da Rocha J., RA Beighton P., Sellars S.L., Thandrayen K., Pettifor J.M., Ramesar R.S.; RT "Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss RT caused by a mutation in RRM2B."; RL Hum. Mutat. 41:1871-1876(2020). CC -!- FUNCTION: Plays a pivotal role in cell survival by repairing damaged CC DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for CC DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free CC radical center required for catalysis. Forms an active ribonucleotide CC reductase (RNR) complex with RRM1 which is expressed both in resting CC and proliferating cells in response to DNA damage. CC {ECO:0000269|PubMed:10716435, ECO:0000269|PubMed:11517226, CC ECO:0000269|PubMed:11719458}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'- CC diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'- CC diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA- CC COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, CC ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10014, CC ECO:0000269|PubMed:16376858}; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; CC Evidence={ECO:0000269|PubMed:19728742}; CC Note=Binds 2 iron ions per subunit. {ECO:0000269|PubMed:19728742}; CC -!- SUBUNIT: Heterotetramer with large (RRM1) subunit. Interacts with CC p53/TP53. Interacts with RRM1 in response to DNA damage. CC {ECO:0000269|PubMed:11517226, ECO:0000269|PubMed:12615712, CC ECO:0000269|PubMed:16376858, ECO:0000269|PubMed:19728742, CC ECO:0000269|Ref.17}. CC -!- INTERACTION: CC Q7LG56; Q13315: ATM; NbExp=3; IntAct=EBI-9009083, EBI-495465; CC Q7LG56; Q00987: MDM2; NbExp=2; IntAct=EBI-9009083, EBI-389668; CC Q7LG56; O43929: ORC4; NbExp=4; IntAct=EBI-9009083, EBI-374889; CC Q7LG56; Q9H4P4: RNF41; NbExp=3; IntAct=EBI-9009083, EBI-2130266; CC Q7LG56; Q7LG56: RRM2B; NbExp=3; IntAct=EBI-9009083, EBI-9009083; CC Q7LG56-1; Q00987: MDM2; NbExp=2; IntAct=EBI-15741413, EBI-389668; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates from CC cytoplasm to nucleus in response to DNA damage. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q7LG56-1; Sequence=Displayed; CC Name=2; Synonyms=Long form; CC IsoId=Q7LG56-2; Sequence=VSP_017670; CC Name=3; Synonyms=Short form gamma; CC IsoId=Q7LG56-3; Sequence=VSP_017669; CC Name=4; Synonyms=Short form beta; CC IsoId=Q7LG56-4; Sequence=VSP_017668; CC Name=5; Synonyms=Short form; CC IsoId=Q7LG56-5; Sequence=VSP_017671, VSP_017672; CC Name=6; CC IsoId=Q7LG56-6; Sequence=VSP_053585; CC -!- TISSUE SPECIFICITY: Widely expressed at a high level in skeletal muscle CC and at a weak level in thymus. Expressed in epithelial dysplasias and CC squamous cell carcinoma. {ECO:0000269|PubMed:14583450}. CC -!- INDUCTION: In response to DNA damage in a wild-type p53/TP53-dependent CC manner. {ECO:0000269|PubMed:10716435}. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 8A (MTDPS8A) CC [MIM:612075]: A disorder due to mitochondrial dysfunction characterized CC by various combinations of neonatal hypotonia, neurological CC deterioration, respiratory distress, lactic acidosis, and renal CC tubulopathy. {ECO:0000269|PubMed:17486094, CC ECO:0000269|PubMed:18504129}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 8B (MTDPS8B) CC [MIM:612075]: A disease due to mitochondrial dysfunction and CC characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, CC cachexia, peripheral neuropathy. {ECO:0000269|PubMed:19667227}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA CC deletions, autosomal dominant, 5 (PEOA5) [MIM:613077]: A disorder CC characterized by progressive weakness of ocular muscles and levator CC muscle of the upper eyelid. In a minority of cases, it is associated CC with skeletal myopathy, which predominantly involves axial or proximal CC muscles and which causes abnormal fatigability and even permanent CC muscle weakness. Ragged-red fibers and atrophy are found on muscle CC biopsy. A large proportion of chronic ophthalmoplegias are associated CC with other symptoms, leading to a multisystemic pattern of this CC disease. Additional symptoms are variable, and may include cataracts, CC hearing loss, sensory axonal neuropathy, ataxia, depression, CC hypogonadism, and parkinsonism. {ECO:0000269|PubMed:19664747}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Rod-cone dystrophy, sensorineural deafness, and Fanconi-type CC renal dysfunction (RCDFRD) [MIM:268315]: An autosomal recessive disease CC characterized by visual impairment due to rod-cone dystrophy, CC sensorineural hearing loss, and Fanconi-type renal dysfunction CC resulting in rickets-like skeletal changes. Death may occur in CC childhood or young adulthood due to renal failure. Disease onset is CC before age 5 years. {ECO:0000269|PubMed:32827185}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 5]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small CC chain family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG65196.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=EAW91842.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/rrm2b/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB036063; BAA92434.1; -; mRNA. DR EMBL; AB036532; BAA92493.1; -; Genomic_DNA. DR EMBL; AB163437; BAD11774.1; -; mRNA. DR EMBL; AB163438; BAD11775.1; -; mRNA. DR EMBL; AB166669; BAD12265.1; -; mRNA. DR EMBL; AB166670; BAD12266.1; -; mRNA. DR EMBL; AB166671; BAD12267.1; -; mRNA. DR EMBL; AK001965; BAA92005.1; -; mRNA. DR EMBL; AK304354; BAG65196.1; ALT_INIT; mRNA. DR EMBL; DC308409; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL137348; CAB70703.2; -; mRNA. DR EMBL; DQ027001; AAY29059.1; -; Genomic_DNA. DR EMBL; AP001328; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP002907; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW91842.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC042468; AAH42468.1; -; mRNA. DR EMBL; BC108261; AAI08262.1; -; mRNA. DR EMBL; BC117496; AAI17497.1; -; mRNA. DR EMBL; BC130628; AAI30629.1; -; mRNA. DR CCDS; CCDS34932.1; -. [Q7LG56-1] DR CCDS; CCDS55267.1; -. [Q7LG56-2] DR PIR; T46249; T46249. DR RefSeq; NP_001165948.1; NM_001172477.1. [Q7LG56-6] DR RefSeq; NP_001165949.1; NM_001172478.1. [Q7LG56-2] DR RefSeq; NP_056528.2; NM_015713.4. [Q7LG56-1] DR PDB; 2VUX; X-ray; 2.80 A; A/B=20-322. DR PDB; 3HF1; X-ray; 2.60 A; A/B=1-351. DR PDB; 4DJN; X-ray; 2.20 A; A/B=13-322. DR PDBsum; 2VUX; -. DR PDBsum; 3HF1; -. DR PDBsum; 4DJN; -. DR AlphaFoldDB; Q7LG56; -. DR SMR; Q7LG56; -. DR BioGRID; 119071; 72. DR ComplexPortal; CPX-369; Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant. DR DIP; DIP-24264N; -. DR DIP; DIP-48627N; -. DR IntAct; Q7LG56; 19. DR STRING; 9606.ENSP00000251810; -. DR BindingDB; Q7LG56; -. DR ChEMBL; CHEMBL3301398; -. DR DrugBank; DB00242; Cladribine. DR GlyGen; Q7LG56; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q7LG56; -. DR PhosphoSitePlus; Q7LG56; -. DR BioMuta; RRM2B; -. DR DMDM; 74727333; -. DR EPD; Q7LG56; -. DR jPOST; Q7LG56; -. DR MassIVE; Q7LG56; -. DR MaxQB; Q7LG56; -. DR PaxDb; 9606-ENSP00000251810; -. DR PeptideAtlas; Q7LG56; -. DR ProteomicsDB; 5837; -. DR ProteomicsDB; 68860; -. [Q7LG56-1] DR ProteomicsDB; 68861; -. [Q7LG56-2] DR ProteomicsDB; 68862; -. [Q7LG56-3] DR ProteomicsDB; 68863; -. [Q7LG56-4] DR ProteomicsDB; 68864; -. [Q7LG56-5] DR Pumba; Q7LG56; -. DR Antibodypedia; 3483; 401 antibodies from 38 providers. DR DNASU; 50484; -. DR Ensembl; ENST00000251810.8; ENSP00000251810.3; ENSG00000048392.13. [Q7LG56-1] DR Ensembl; ENST00000395912.6; ENSP00000379248.2; ENSG00000048392.13. [Q7LG56-2] DR Ensembl; ENST00000519317.5; ENSP00000430641.1; ENSG00000048392.13. [Q7LG56-3] DR Ensembl; ENST00000519962.5; ENSP00000429140.1; ENSG00000048392.13. [Q7LG56-4] DR Ensembl; ENST00000522394.1; ENSP00000429578.1; ENSG00000048392.13. [Q7LG56-5] DR GeneID; 50484; -. DR KEGG; hsa:50484; -. DR MANE-Select; ENST00000251810.8; ENSP00000251810.3; NM_015713.5; NP_056528.2. DR UCSC; uc003ykn.4; human. [Q7LG56-1] DR AGR; HGNC:17296; -. DR CTD; 50484; -. DR DisGeNET; 50484; -. DR GeneCards; RRM2B; -. DR GeneReviews; RRM2B; -. DR HGNC; HGNC:17296; RRM2B. DR HPA; ENSG00000048392; Low tissue specificity. DR MalaCards; RRM2B; -. DR MIM; 268315; phenotype. DR MIM; 604712; gene. DR MIM; 612075; phenotype. DR MIM; 613077; phenotype. DR neXtProt; NX_Q7LG56; -. DR OpenTargets; ENSG00000048392; -. DR Orphanet; 329336; Adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy. DR Orphanet; 254892; Autosomal dominant progressive external ophthalmoplegia. DR Orphanet; 480; Kearns-Sayre syndrome. DR Orphanet; 255235; Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy. DR Orphanet; 298; Mitochondrial neurogastrointestinal encephalomyopathy. DR PharmGKB; PA34866; -. DR VEuPathDB; HostDB:ENSG00000048392; -. DR eggNOG; KOG1567; Eukaryota. DR GeneTree; ENSGT00390000013305; -. DR HOGENOM; CLU_035339_2_0_1; -. DR InParanoid; Q7LG56; -. DR OMA; LEPMFLG; -. DR OrthoDB; 5487627at2759; -. DR PhylomeDB; Q7LG56; -. DR TreeFam; TF300465; -. DR BRENDA; 1.17.4.1; 2681. DR PathwayCommons; Q7LG56; -. DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR SignaLink; Q7LG56; -. DR SIGNOR; Q7LG56; -. DR BioGRID-ORCS; 50484; 17 hits in 1170 CRISPR screens. DR ChiTaRS; RRM2B; human. DR EvolutionaryTrace; Q7LG56; -. DR GeneWiki; RRM2B; -. DR GenomeRNAi; 50484; -. DR Pharos; Q7LG56; Tbio. DR PRO; PR:Q7LG56; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q7LG56; Protein. DR Bgee; ENSG00000048392; Expressed in secondary oocyte and 188 other cell types or tissues. DR ExpressionAtlas; Q7LG56; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; ISS:ComplexPortal. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IBA:GO_Central. DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; IDA:ComplexPortal. DR GO; GO:0009200; P:deoxyribonucleoside triphosphate metabolic process; IEA:Ensembl. DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IBA:GO_Central. DR GO; GO:0006281; P:DNA repair; IDA:ComplexPortal. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; NAS:ComplexPortal. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:ComplexPortal. DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IEA:Ensembl. DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; IDA:ComplexPortal. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IDA:ComplexPortal. DR GO; GO:0003014; P:renal system process; IEA:Ensembl. DR GO; GO:0014075; P:response to amine; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; IDA:ComplexPortal. DR CDD; cd01049; RNRR2; 1. DR Gene3D; 1.10.620.20; Ribonucleotide Reductase, subunit A; 1. DR InterPro; IPR009078; Ferritin-like_SF. DR InterPro; IPR012348; RNR-like. DR InterPro; IPR033909; RNR_small. DR InterPro; IPR030475; RNR_small_AS. DR InterPro; IPR000358; RNR_small_fam. DR PANTHER; PTHR23409; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE SMALL CHAIN; 1. DR PANTHER; PTHR23409:SF19; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE SUBUNIT M2 B; 1. DR Pfam; PF00268; Ribonuc_red_sm; 1. DR SUPFAM; SSF47240; Ferritin-like; 1. DR PROSITE; PS00368; RIBORED_SMALL; 1. DR Genevisible; Q7LG56; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Deafness; KW Deoxyribonucleotide synthesis; Disease variant; DNA damage; DNA repair; KW Iron; Metal-binding; Neuropathy; Nucleus; Oxidoreductase; KW Primary mitochondrial disease; Progressive external ophthalmoplegia; KW Reference proteome. FT CHAIN 1..351 FT /note="Ribonucleoside-diphosphate reductase subunit M2 B" FT /id="PRO_0000228150" FT REGION 1..32 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 138 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014" FT BINDING 100 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="1" FT BINDING 131 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="1" FT BINDING 131 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT BINDING 134 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="1" FT BINDING 194 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT BINDING 228 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT BINDING 231 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_label="2" FT VAR_SEQ 1..16 FT /note="MGDPERPEAAGLDQDE -> MLLLRLPPHRSHASPLDCKLQDRCRKCYSPRS FT GQACPPALAAAWLRRCERRGGRPRGGRRKELTLGLRPARCSAPGPAKDDAWRPQAG FT (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_053585" FT VAR_SEQ 17..301 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_017668" FT VAR_SEQ 17..228 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_017669" FT VAR_SEQ 17..68 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_017670" FT VAR_SEQ 42..43 FT /note="FV -> SF (in isoform 5)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_017671" FT VAR_SEQ 44..351 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_017672" FT VARIANT 33 FT /note="P -> S (found in a patient with combined respiratory FT complex deficiencies, muscle weakness and hearing loss; FT uncertain significance; dbSNP:rs387906892)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076280" FT VARIANT 64 FT /note="W -> R (in MTDPS8A; dbSNP:rs515726182)" FT /evidence="ECO:0000269|PubMed:17486094" FT /id="VAR_046217" FT VARIANT 85 FT /note="Missing (in MTDPS8A; dbSNP:rs515726184)" FT /evidence="ECO:0000269|PubMed:17486094" FT /id="VAR_046218" FT VARIANT 110 FT /note="R -> H (in MTDPS8B; dbSNP:rs267607025)" FT /evidence="ECO:0000269|PubMed:19667227" FT /id="VAR_065122" FT VARIANT 115 FT /note="V -> L (in colorectal adenocarcinomas cell line; FT loss of ribonucleotide reductase activity)" FT /evidence="ECO:0000269|PubMed:11719458" FT /id="VAR_025699" FT VARIANT 121 FT /note="R -> H (in MTDPS8B; dbSNP:rs267607024)" FT /evidence="ECO:0000269|PubMed:19667227" FT /id="VAR_065123" FT VARIANT 194 FT /note="E -> G (in MTDPS8A; dbSNP:rs515726191)" FT /evidence="ECO:0000269|PubMed:17486094" FT /id="VAR_046219" FT VARIANT 194 FT /note="E -> K (in MTDPS8A; dbSNP:rs121918308)" FT /evidence="ECO:0000269|PubMed:17486094" FT /id="VAR_046220" FT VARIANT 224 FT /note="I -> S (in MTDPS8A; without tubulopathy; FT dbSNP:rs515726196)" FT /evidence="ECO:0000269|PubMed:18504129" FT /id="VAR_046221" FT VARIANT 236 FT /note="C -> F (in MTDPS8A; dbSNP:rs121918309)" FT /evidence="ECO:0000269|PubMed:17486094" FT /id="VAR_046222" FT VARIANT 262 FT /note="E -> D (in RCDFRD; dbSNP:rs1810682433)" FT /evidence="ECO:0000269|PubMed:32827185" FT /id="VAR_086956" FT VARIANT 282 FT /note="M -> I (in MTDPS8A; without tubulopathy; FT dbSNP:rs182614164)" FT /evidence="ECO:0000269|PubMed:18504129" FT /id="VAR_046223" FT VARIANT 317 FT /note="L -> V (in MTDPS8A; without tubulopathy; FT dbSNP:rs515726198)" FT /evidence="ECO:0000269|PubMed:18504129" FT /id="VAR_046224" FT CONFLICT 277 FT /note="M -> V (in Ref. 3; BAA92005)" FT /evidence="ECO:0000305" FT HELIX 29..31 FT /evidence="ECO:0007829|PDB:4DJN" FT TURN 33..35 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 37..39 FT /evidence="ECO:0007829|PDB:4DJN" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 50..61 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 66..68 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 74..78 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 83..109 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 111..114 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 118..145 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 149..156 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 158..161 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 163..177 FT /evidence="ECO:0007829|PDB:4DJN" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 183..195 FT /evidence="ECO:0007829|PDB:4DJN" FT TURN 196..198 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 199..210 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 215..240 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 248..267 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 272..275 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 279..296 FT /evidence="ECO:0007829|PDB:4DJN" FT HELIX 310..312 FT /evidence="ECO:0007829|PDB:4DJN" SQ SEQUENCE 351 AA; 40737 MW; 6D008687EEF40994 CRC64; MGDPERPEAA GLDQDERSSS DTNESEIKSN EEPLLRKSSR RFVIFPIQYP DIWKMYKQAQ ASFWTAEEVD LSKDLPHWNK LKADEKYFIS HILAFFAASD GIVNENLVER FSQEVQVPEA RCFYGFQILI ENVHSEMYSL LIDTYIRDPK KREFLFNAIE TMPYVKKKAD WALRWIADRK STFGERVVAF AAVEGVFFSG SFAAIFWLKK RGLMPGLTFS NELISRDEGL HCDFACLMFQ YLVNKPSEER VREIIVDAVK IEQEFLTEAL PVGLIGMNCI LMKQYIEFVA DRLLVELGFS KVFQAENPFD FMENISLEGK TNFFEKRVSE YQRFAVMAET TDNVFTLDAD F //