P70388 (RAD50_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 99.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: DNA repair protein RAD50 Short name=mRad50 EC=3.6.-.- | ||
| Gene names |
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| Organism | Mus musculus (Mouse) [Reference proteome] | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus![]() |
Protein attributes
| Sequence length | 1312 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation By similarity. Ref.4 Ref.5 |
| Cofactor | Binds 1 zinc ion per homodimer By similarity. |
| Subunit structure | Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11A and NBN. Found in a complex with TERF2. Interacts with RINT1. Interacts with BRCA1 via its N-terminal domain. Interacts with DCLRE1C/Artemis By similarity. |
| Subcellular location | Nucleus By similarity. Chromosome › telomere By similarity. Note: Localizes to discrete nuclear foci after treatment with genotoxic agents By similarity. |
| Tissue specificity | In adult, it is expressed at very low level in most tissues, except in heart, lung and aorta. Expressed at high level in testis. Ref.1 |
| Developmental stage | Widely expressed. Expressed at higher level in heart, liver and thymus from E18. By neonatal day 1.5, it decreases in brain, liver, gut and skin, while it is expressed in spleen. Ref.1 |
| Domain | The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11A homodimer By similarity. |
| Disruption phenotype | Defects cause embryonic stem cell lethality, abnormal embryonic development and sensitivity to ionizing radiation. Ref.4 |
| Sequence similarities | Belongs to the SMC family. RAD50 subfamily. Contains 1 zinc-hook domain. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P70388-1) 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: P70388-2) The sequence of this isoform differs from the canonical sequence as follows: 485-545: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: P70388-3) Also known as: 3.1 kb splice variant; The sequence of this isoform differs from the canonical sequence as follows: 1-886: Missing. | ||||||
| Isoform 4 (identifier: P70388-4) Also known as: 1.6 kb splice variant; The sequence of this isoform differs from the canonical sequence as follows: 485-496: ERELSKAEKNSS → IYFLELVRWLSG 497-1312: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1312 | 1312 | DNA repair protein RAD50 | PRO_0000138642 | |||||
Regions | |||||||||
| Domain | 635 – 734 | 100 | Zinc-hook | ||||||
| Nucleotide binding | 36 – 43 | 8 | ATP Potential | ||||||
| Coiled coil | 200 – 532 | 333 | Potential | ||||||
| Coiled coil | 635 – 673 | 39 | Potential | ||||||
| Coiled coil | 706 – 734 | 29 | Potential | ||||||
| Coiled coil | 776 – 942 | 167 | Potential | ||||||
| Coiled coil | 1043 – 1075 | 33 | Potential | ||||||
| Compositional bias | 1201 – 1238 | 38 | Ala/Asp-rich (DA-box) | ||||||
Sites | |||||||||
| Metal binding | 681 | 1 | Zinc By similarity | ||||||
| Metal binding | 684 | 1 | Zinc By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 237 | 1 | Phosphoserine Ref.6 | ||||||
| Modified residue | 635 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 690 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 959 | 1 | N6-acetyllysine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 886 | 886 | Missing in isoform 3. | VSP_012592 | |||||
| Alternative sequence | 485 – 545 | 61 | Missing in isoform 2. | VSP_012593 | |||||
| Alternative sequence | 485 – 496 | 12 | ERELS…EKNSS → IYFLELVRWLSG in isoform 4. | VSP_012594 | |||||
| Alternative sequence | 497 – 1312 | 816 | Missing in isoform 4. | VSP_012595 | |||||
Experimental info | |||||||||
| Mutagenesis | 22 | 1 | K → M in Rad50S; hypomorphic allele that induces growth defects and cancer predisposition. Homozygous individuals die with complete bone marrow depletion as a result of progressive hematopoietic stem cell failure. Ref.5 | ||||||
| Sequence conflict | 97 | 1 | H → Q in BAB31030. Ref.2 | ||||||
| Sequence conflict | 200 | 1 | G → V in AAH58180. Ref.3 | ||||||
| Sequence conflict | 474 | 1 | I → V in BAC40074. Ref.2 | ||||||
| Sequence conflict | 718 | 1 | E → A in BAC40074. Ref.2 | ||||||
| Sequence conflict | 719 | 1 | L → K in AAH58180. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Mouse RAD50 has limited epitopic homology to p53 and is expressed in the adult myocardium." Kim K.K., Daud A.I., Wong S.C., Pajak L., Tsai S.-C., Wang H., Henzel W.J., Field L.J. J. Biol. Chem. 271:29255-29264(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), PROTEIN SEQUENCE OF 113-120; 132-140; 175-202; 230-248; 295-310; 815-832; 840-845; 1012-1026 AND 1079-1089, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [2] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-214 AND 443-743 (ISOFORM 1). Strain: C57BL/6J and NOD. Tissue: Thymus. |
| [3] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-722 (ISOFORM 2). Strain: NMRI. Tissue: Mammary tumor. |
| [4] | "Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation." Luo G., Yao M.S., Bender C.F., Mills M., Bladl A.R., Bradley A., Petrini J.H.J. Proc. Natl. Acad. Sci. U.S.A. 96:7376-7381(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE. |
| [5] | "Cancer predisposition and hematopoietic failure in Rad50(S/S) mice." Bender C.F., Sikes M.L., Sullivan R., Huye L.E., Le Beau M.M., Roth D.B., Mirzoeva O.K., Oltz E.M., Petrini J.H.J. Genes Dev. 16:2237-2251(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-22. |
| [6] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U66887 mRNA. Translation: AAC52894.1. AK018001 mRNA. Translation: BAB31030.1. AK087982 mRNA. Translation: BAC40074.1. BC058180 mRNA. Translation: AAH58180.1. |
| IPI | IPI00108335. IPI00551249. IPI00551329. IPI00551367. |
| PIR | T30845. |
| UniGene | Mm.4888. |
3D structure databases | |
| ProteinModelPortal | P70388. |
| SMR | P70388. Positions 7-67. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-46805N. |
| IntAct | P70388. 2 interactions. |
PTM databases | |
| PhosphoSite | P70388. |
Proteomic databases | |
| PaxDb | P70388. |
| PRIDE | P70388. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| UCSC | uc011xus.1. mouse. |
Organism-specific databases | |
| MGI | MGI:109292. Rad50. |
Phylogenomic databases | |
| eggNOG | COG0419. |
| HOGENOM | HOG000090195. |
| HOVERGEN | HBG058033. |
| InParanoid | P70388. |
| OrthoDB | EOG45HRWK. |
Gene expression databases | |
| CleanEx | MM_RAD50. |
| Genevestigator | P70388. |
| GermOnline | ENSMUSG00000020380. Mus musculus. |
Family and domain databases | |
| InterPro | IPR004584. Rad50. IPR007517. Rad50_Zn_hook. IPR013134. Zn_hook_Rad50. [Graphical view] |
| PANTHER | PTHR18867. PTHR18867. 1 hit. |
| Pfam | PF04423. Rad50_zn_hook. 1 hit. [Graphical view] |
| TIGRFAMs | TIGR00606. rad50. 1 hit. |
| PROSITE | PS51131. ZN_HOOK. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| SOURCE | Search... |
Entry information
| Entry name | RAD50_MOUSE | ||||||||
| Accession | Primary (citable) accession number: P70388 Secondary accession number(s): Q6PEB0, Q8C2T7, Q9CU59 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
