RIR2B_HUMAN
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 03-AUG-2022, entry version 180.
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).
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 -!- PATHWAY: Genetic information processing; DNA replication.
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 -!- 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/";
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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; 64.
DR ComplexPortal; CPX-369; Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant.
DR DIP; DIP-24264N; -.
DR DIP; DIP-48627N; -.
DR IntAct; Q7LG56; 16.
DR STRING; 9606.ENSP00000251810; -.
DR BindingDB; Q7LG56; -.
DR ChEMBL; CHEMBL3301398; -.
DR DrugBank; DB00242; Cladribine.
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; Q7LG56; -.
DR PeptideAtlas; Q7LG56; -.
DR PRIDE; 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 Antibodypedia; 3483; 363 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 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; 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; APELQIY; -.
DR OrthoDB; 680824at2759; -.
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 UniPathway; UPA00326; -.
DR BioGRID-ORCS; 50484; 16 hits in 1084 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 186 other tissues.
DR ExpressionAtlas; Q7LG56; baseline and differential.
DR Genevisible; Q7LG56; HS.
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: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; IC: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; -; 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; PTHR23409; 1.
DR Pfam; PF00268; Ribonuc_red_sm; 1.
DR SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS00368; RIBORED_SMALL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm;
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 unknown pathological 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 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
