Reviewed,
UniProtKB/Swiss-Prot Q7LG56 (RIR2B_HUMAN)
Last modified
November 3, 2009.
Version 63.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Ribonucleoside-diphosphate reductase subunit M2 B EC=1.17.4.1 Alternative name(s): TP53-inducible ribonucleotide reductase M2 B p53-inducible ribonucleotide reductase small subunit 2-like protein Short name=p53R2 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 351 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. Ref.1 Ref.7 Ref.8 |
| Catalytic activity | 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin. |
| Cofactor | Binds 2 iron ions per subunit By similarity. |
| Pathway | |
| Subunit structure | Heterotetramer with large (RRM1) subunit. Interacts with p53/TP53. Interacts with RRM1 in response to DNA damage. Ref.7 Ref.9 |
| Subcellular location | Cytoplasm. Nucleus. Note: Translocates from cytoplasm to nucleus in response to DNA damage. Ref.8 Ref.9 |
| 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. Ref.10 |
| Induction | In response to DNA damage in a wild-type p53/TP53-dependent manner. Ref.1 |
| Involvement in 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. Ref.12 Ref.13 |
| Sequence similarities | Belongs to the ribonucleoside diphosphate reductase small chain family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | DNA damage DNA repair DNA replication |
| Cellular component | Cytoplasm Nucleus |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| Ligand | Iron Metal-binding |
| Molecular function | Oxidoreductase |
| Technical term | 3D-structure Complete proteome |
| Gene Ontology (GO) | |
| Biological process | DNA repair Inferred from electronic annotation. Source: UniProtKB-KW deoxyribonucleoside diphosphate metabolic processInferred from electronic annotation. Source: InterPro oxidation reductionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleusInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoside-diphosphate reductase activityInferred from electronic annotation. Source: EC |
| Complete GO annotation... | |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q7LG56-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q7LG56-2) Also known as: Long form; The sequence of this isoform differs from the canonical sequence as follows: 17-68: Missing. | ||||||
| Isoform 3 (identifier: Q7LG56-3) Also known as: Short form gamma; The sequence of this isoform differs from the canonical sequence as follows: 17-228: Missing. | ||||||
| Isoform 4 (identifier: Q7LG56-4) Also known as: Short form beta; The sequence of this isoform differs from the canonical sequence as follows: 17-301: Missing. | ||||||
| Isoform 5 (identifier: Q7LG56-5) Also known as: Short form; The sequence of this isoform differs from the canonical sequence as follows: 42-43: FV → SF 44-351: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 351 | 351 | Ribonucleoside-diphosphate reductase subunit M2 B | PRO_0000228150 | ||||||||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||||||||
| Active site | 138 | 1 | By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 100 | 1 | Iron 1 By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 131 | 1 | Iron 1 By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 131 | 1 | Iron 2 By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 134 | 1 | Iron 1 By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 194 | 1 | Iron 2 By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 228 | 1 | Iron 2 By similarity | |||||||||||||||||||||||||||||||||||||
| Metal binding | 231 | 1 | Iron 2 By similarity | |||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 17 – 301 | 285 | Missing in isoform 4. | VSP_017668 | ||||||||||||||||||||||||||||||||||||
| Alternative sequence | 17 – 228 | 212 | Missing in isoform 3. | VSP_017669 | ||||||||||||||||||||||||||||||||||||
| Alternative sequence | 17 – 68 | 52 | Missing in isoform 2. | VSP_017670 | ||||||||||||||||||||||||||||||||||||
| Alternative sequence | 42 – 43 | 2 | FV → SF in isoform 5. | VSP_017671 | ||||||||||||||||||||||||||||||||||||
| Alternative sequence | 44 – 351 | 308 | Missing in isoform 5. | VSP_017672 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 64 | 1 | W → R in EMDSRT. Ref.12 | VAR_046217 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 85 | 1 | Missing in EMDSRT. | VAR_046218 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 115 | 1 | V → L in colorectal adenocarcinomas cell line; loss of ribonucleotide reductase activity. Ref.8 | VAR_025699 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 194 | 1 | E → G in EMDSRT. Ref.12 | VAR_046219 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 194 | 1 | E → K in EMDSRT. Ref.12 | VAR_046220 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 224 | 1 | I → S in EMDSRT; without tubulopathy. Ref.13 | VAR_046221 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 236 | 1 | C → F in EMDSRT. Ref.12 | VAR_046222 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 282 | 1 | M → I in EMDSRT; without tubulopathy. Ref.13 | VAR_046223 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 317 | 1 | L → V in EMDSRT; without tubulopathy. Ref.13 | VAR_046224 | ||||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 277 | 1 | M → V in BAA92005. Ref.3 | |||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||
| Turn | 33 – 35 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 50 – 61 | 12 | ||||||||||||||||||||||||||||||||||||||
| Helix | 66 – 68 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 75 – 80 | 6 | ||||||||||||||||||||||||||||||||||||||
| Helix | 83 – 98 | 16 | ||||||||||||||||||||||||||||||||||||||
| Helix | 107 – 114 | 8 | ||||||||||||||||||||||||||||||||||||||
| Helix | 118 – 145 | 28 | ||||||||||||||||||||||||||||||||||||||
| Helix | 149 – 161 | 13 | ||||||||||||||||||||||||||||||||||||||
| Helix | 163 – 175 | 13 | ||||||||||||||||||||||||||||||||||||||
| Turn | 176 – 178 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 183 – 195 | 13 | ||||||||||||||||||||||||||||||||||||||
| Turn | 196 – 198 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 199 – 210 | 12 | ||||||||||||||||||||||||||||||||||||||
| Helix | 215 – 239 | 25 | ||||||||||||||||||||||||||||||||||||||
| Helix | 248 – 267 | 20 | ||||||||||||||||||||||||||||||||||||||
| Helix | 272 – 275 | 4 | ||||||||||||||||||||||||||||||||||||||
| Helix | 279 – 296 | 18 | ||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "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 404:42-49(2000) [PubMed: 10716435] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, INDUCTION. |
| [2] | "Homo sapiens p53-inducible ribonucleotide reductase small subunit 2 splicing variants." Ugai H., Yokoyama K.K. Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5). |
| [3] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta. |
| [4] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Amygdala. |
| [5] | NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Eye. |
| [7] | "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., Haakansson P., Voevodskaya N., Fridd S., Graeslund A., Arakawa H., Nakamura Y., Thelander L. J. Biol. Chem. 276:40647-40651(2001) [PubMed: 11517226] [Abstract] Cited for: FUNCTION, SUBUNIT. |
| [8] | "p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint." Yamaguchi T., Matsuda K., Sagiya Y., Iwadate M., Fujino M.A., Nakamura Y., Arakawa H. Cancer Res. 61:8256-8262(2001) [PubMed: 11719458] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT LEU-115. |
| [9] | "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. 63:980-986(2003) [PubMed: 12615712] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TP53 AND RRM1. |
| [10] | "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 E.B., Luh F., Yen Y. Cancer Res. 63:6583-6594(2003) [PubMed: 14583450] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [11] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [12] | "Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion." Bourdon A., Minai L., Serre V., Jais J.-P., Sarzi E., Aubert S., Chretien D., de Lonlay P., Paquis-Flucklinger V., Arakawa H., Nakamura Y., Munnich A., Roetig A. Nat. Genet. 39:776-780(2007) [PubMed: 17486094] [Abstract] Cited for: VARIANTS EMDSRT ARG-64; GLU-85 DEL; GLY-194; LYS-194 AND PHE-236. |
| [13] | "Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene." Bornstein B., Area E., Flanigan K.M., Ganesh J., Jayakar P., Swoboda K.J., Coku J., Naini A., Shanske S., Tanji K., Hirano M., DiMauro S. Neuromuscul. Disord. 18:453-459(2008) [PubMed: 18504129] [Abstract] Cited for: VARIANTS EMDSRT SER-224; ILE-282 AND VAL-317. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AB036063 mRNA. Translation: BAA92434.1. AB036532 Genomic DNA. Translation: BAA92493.1. AB163437 mRNA. Translation: BAD11774.1. AB163438 mRNA. Translation: BAD11775.1. AB166669 mRNA. Translation: BAD12265.1. AB166670 mRNA. Translation: BAD12266.1. AB166671 mRNA. Translation: BAD12267.1. AK001965 mRNA. Translation: BAA92005.1. AL137348 mRNA. Translation: CAB70703.2. DQ027001 Genomic DNA. Translation: AAY29059.1. BC042468 mRNA. Translation: AAH42468.1. BC108261 mRNA. Translation: AAI08262.1. BC117496 mRNA. Translation: AAI17497.1. BC130628 mRNA. Translation: AAI30629.1. | |||||||||||||
| IPI | IPI00100213. IPI00438859. IPI00438860. IPI00735900. IPI00741117. | ||||||||||||
| PIR | T46249. | ||||||||||||
| RefSeq | NP_056528.2. | ||||||||||||
| UniGene | Hs.512592 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| SMR | Q7LG56. Positions 31-313. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| STRING | Q7LG56. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q7LG56. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q7LG56. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000251810; ENSP00000251810; ENSG00000048392; Homo sapiens. [Genome view] ENST00000395908; ENSP00000379244; ENSG00000048392; Homo sapiens. [Genome view] ENST00000395910; ENSP00000379246; ENSG00000048392; Homo sapiens. [Genome view] ENST00000395912; ENSP00000379248; ENSG00000048392; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 50484. | ||||||||||||
| KEGG | hsa:50484. | ||||||||||||
| UCSC | uc003ykn.1. human. uc010mbv.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 50484. | ||||||||||||
| GeneCards | GC08M103285. | ||||||||||||
| H-InvDB | HIX0007697. | ||||||||||||
| HGNC | HGNC:17296. RRM2B. | ||||||||||||
| HPA | CAB006854. | ||||||||||||
| MIM | 604712. gene. 612075. phenotype. | ||||||||||||
| PharmGKB | PA34866. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOVERGEN | Q7LG56. | ||||||||||||
| OMA | ENLVQRF. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 1.17.4.1. 247. | ||||||||||||
| Reactome | REACT_1698. Metablism of nucleotides. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q7LG56. | ||||||||||||
| Bgee | Q7LG56. | ||||||||||||
| Genevestigator | Q7LG56. | ||||||||||||
| GermOnline | ENSG00000048392. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR012348. Ribncl_red_rel. IPR000358. Ribonucl_redctse. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:1.10.620.20. Ribncl_red_rel. 1 hit. | ||||||||||||
| PANTHER | PTHR23409. Ribonucl_redctse. 1 hit. | ||||||||||||
| Pfam | PF00268. Ribonuc_red_sm. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS00368. RIBORED_SMALL. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 53036. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | RIR2B_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q7LG56 Secondary accession number(s): Q17R22 Q9NUW3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 8 Human chromosome 8: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


