P70388 · RAD50_MOUSE
- ProteinDNA repair protein RAD50
- GeneRad50
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1312 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PubMed:10377422, PubMed:12208847).
The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (By similarity).
The complex 1 mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is 2 required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (By similarity).
The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (By similarity).
Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (By similarity).
RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity).
The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (By similarity).
The MRN complex is also required for the processing of R-loops. In telomeres the MRN complex may modulate t-loop formation (By similarity).
The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (By similarity).
The complex 1 mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is 2 required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (By similarity).
The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (By similarity).
Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (By similarity).
RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity).
The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (By similarity).
The MRN complex is also required for the processing of R-loops. In telomeres the MRN complex may modulate t-loop formation (By similarity).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphate
Cofactor
Note: Binds 1 zinc ion per homodimer.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 13 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 38 | ATP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 39 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 41 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 42 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 43 | ATP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 43 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 44 | ATP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 67 | ATP (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 69 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 159 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 159 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 681 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 684 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA repair protein RAD50
- EC number
- Short namesmRad50
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP70388
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to discrete nuclear foci after treatment with genotoxic agents. Localizes to DNA double-strand breaks (DSBs).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Defects cause embryonic stem cell lethality, abnormal embryonic development and sensitivity to ionizing radiation.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 22 | 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. | ||||
Sequence: K → M |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000138642 | 1-1312 | DNA repair protein RAD50 | |||
Sequence: MSRIEKMSILGVRSFGIEDKDKQIISFFSPLTILVGPNGAGKTTIIECLKYICTGDFPPGTKGNTFVHDPKVAQETDVRAQIRLQFRDVNGEMVAVHRSMLCSQKNKKTEFKTLEGVITRMKHGEKVSLSSKCAEIDREMISCLGVSKSVLNNVIFCHQEDSNWPLSEGKALKQKFDEIFSATRYIKALDTLRQVRQTQGQKVKECQTELKYLKQNKEKACEIRDQITSKEAQLASSQEIVRSYEDELEPLKNRLKEIEHNLSKIMKLDNEIKALESRKKQMEKDNSELEQKMEKVFQGTDEQLNDLYHNHQRTVREKERRLVDCQRELEKLNKEARLLNQEKAELLVEQGRLQLQADRHQEHIRARDSLIQSLATHLELDGFERGPFSERQIKNFHELVKERQEREAKTASQLLSDLTDKEALKQRQLDELRDRKSGLGRTIELKTEILTKKQSELRHVRSELQQLEGSSDRILELDQELTKAERELSKAEKNSSIETLKAEVMSLQNEKADLDRSLRKLDQEMEQLNHHTTTRTQMEMLTKDKTDKDEQIRKIKSRHSDELTSLLGYFPNKKQLEDWLHSKSKEINQTRDRLAKLNKELASAEQNKNHINNELKKKEEQLSSYEDKLFDVCGSQDLESDLGRLKEEIEKSSKQRAMLAGATAVYSQFITQLTDENQSCCPVCQRVFQTEAELQEVISDLQSKLRLAPDKLKSTESELKKKERRRDEMLGLVPVRQSIIDLKEKEIPELRNRLQSVNRDIQRLKNDIEEQETLLGTIMPEEESAKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGVDLDRTVQQVNQEKQEKQHRLDTVTSKIELNRKLIQDQQEQIQHLKSKTNELKSEKLQIATNLQRRQQMEEQSVELSTEVQSLNREIKDAKEQISPLETALEKLQQEKEELIHRKHTSNKMAQDKINDIKEKVKNIHGYMKDIENYIQDGKDDYKKQKETELNGVAVQLNECEKHREKINKDMGTMRQDIDTQKIQERWLQDNLTLRKRRDELKEVEEEPKQHLKEMGQMQVLQMKNEHQKLEENIDTIKRNHSLALGRQKGYEDEILHFKKELREPQFRDAEEKYREMMIVMRTTELVNKDLDIYYKTLDQAIMKFHSMKMEEINKIIRDLWRSTYRGQDIEYIEIRSDADENVSASDKRRNYNYRVVMLKGDTALDMRGRCSAGQKVLASLIIRLALAETFCLNCGILALDEPTTNLDRENIESLAHALVEIIKSRSQQRNFQLLVITHDEDFVELLGRSEYVEKFYRVKKNMDQCSEIVKCSISSLGSYVH | ||||||
Modified residue | 635 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 690 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 959 | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Phosphorylation at Ser-635 by ATM in response to DNA damage is required for double-strand break (DSB) repair.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Developmental stage
Widely expressed. Expressed at higher level in heart, liver and thymus from 18 dpc. By neonatal day 1.5, it decreases in brain, liver, gut and skin, while it is expressed in spleen.
Interaction
Subunit
Component of the MRN complex composed of two heterodimers RAD50 and MRE11 associated with a single NBN (By similarity).
The MRN complexes dimerize on DNA to form joined MRN-MRN oligomers required for DNA double-strand break repair (By similarity).
As part of the MRN complex, interacts with MCM8 and MCM9; the interaction recruits the complex to DNA repair sites (By similarity).
Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (By similarity).
Found in a complex with TERF2 (By similarity).
Interacts with RINT1 (By similarity).
Interacts with BRCA1 via its N-terminal domain (By similarity).
Interacts with DCLRE1C/Artemis (By similarity).
Interacts with MRNIP (By similarity).
Interacts with CYREN (via XLF motif) (PubMed:30017584).
Interacts with C1QBP and MRE11; interaction takes place in absence of DNA damage to form the MRC (MRE11-RAD50-C1QBP) complex that inhibits the activity of MRE11 (By similarity).
The MRN complexes dimerize on DNA to form joined MRN-MRN oligomers required for DNA double-strand break repair (By similarity).
As part of the MRN complex, interacts with MCM8 and MCM9; the interaction recruits the complex to DNA repair sites (By similarity).
Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (By similarity).
Found in a complex with TERF2 (By similarity).
Interacts with RINT1 (By similarity).
Interacts with BRCA1 via its N-terminal domain (By similarity).
Interacts with DCLRE1C/Artemis (By similarity).
Interacts with MRNIP (By similarity).
Interacts with CYREN (via XLF motif) (PubMed:30017584).
Interacts with C1QBP and MRE11; interaction takes place in absence of DNA damage to form the MRC (MRE11-RAD50-C1QBP) complex that inhibits the activity of MRE11 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for coiled coil, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Coiled coil | 200-532 | |||||
Sequence: GQKVKECQTELKYLKQNKEKACEIRDQITSKEAQLASSQEIVRSYEDELEPLKNRLKEIEHNLSKIMKLDNEIKALESRKKQMEKDNSELEQKMEKVFQGTDEQLNDLYHNHQRTVREKERRLVDCQRELEKLNKEARLLNQEKAELLVEQGRLQLQADRHQEHIRARDSLIQSLATHLELDGFERGPFSERQIKNFHELVKERQEREAKTASQLLSDLTDKEALKQRQLDELRDRKSGLGRTIELKTEILTKKQSELRHVRSELQQLEGSSDRILELDQELTKAERELSKAEKNSSIETLKAEVMSLQNEKADLDRSLRKLDQEMEQLNHHT | ||||||
Coiled coil | 635-673 | |||||
Sequence: SQDLESDLGRLKEEIEKSSKQRAMLAGATAVYSQFITQL | ||||||
Domain | 635-734 | Zinc-hook | ||||
Sequence: SQDLESDLGRLKEEIEKSSKQRAMLAGATAVYSQFITQLTDENQSCCPVCQRVFQTEAELQEVISDLQSKLRLAPDKLKSTESELKKKERRRDEMLGLVP | ||||||
Coiled coil | 706-734 | |||||
Sequence: RLAPDKLKSTESELKKKERRRDEMLGLVP | ||||||
Coiled coil | 776-942 | |||||
Sequence: GTIMPEEESAKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGVDLDRTVQQVNQEKQEKQHRLDTVTSKIELNRKLIQDQQEQIQHLKSKTNELKSEKLQIATNLQRRQQMEEQSVELSTEVQSLNREIKDAKEQISPLETALEKLQQEKEELIHRKHTSNKMAQD | ||||||
Coiled coil | 1043-1075 | |||||
Sequence: KEMGQMQVLQMKNEHQKLEENIDTIKRNHSLAL |
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 MRE11 homodimer.
Sequence similarities
Belongs to the SMC family. RAD50 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
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.
- Name1
- Length1,312
- Mass (Da)153,488
- Last updated1997-02-01 v1
- Checksum4AF9AF9AD9E1D7A2
P70388-2
- Name2
- Differences from canonical
- 485-545: Missing
P70388-3
- Name3
- Synonyms3.1 kb splice variant
- Differences from canonical
- 1-886: Missing
P70388-4
- Name4
- Synonyms1.6 kb splice variant
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_012592 | 1-886 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 97 | in Ref. 2; BAB31030 | ||||
Sequence: H → Q | ||||||
Sequence conflict | 200 | in Ref. 3; AAH58180 | ||||
Sequence: G → V | ||||||
Sequence conflict | 474 | in Ref. 2; BAC40074 | ||||
Sequence: I → V | ||||||
Alternative sequence | VSP_012594 | 485-496 | in isoform 4 | |||
Sequence: ERELSKAEKNSS → IYFLELVRWLSG | ||||||
Alternative sequence | VSP_012593 | 485-545 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_012595 | 497-1312 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 718 | in Ref. 2; BAC40074 | ||||
Sequence: E → A | ||||||
Sequence conflict | 719 | in Ref. 3; AAH58180 | ||||
Sequence: L → K |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U66887 EMBL· GenBank· DDBJ | AAC52894.1 EMBL· GenBank· DDBJ | mRNA | ||
AK018001 EMBL· GenBank· DDBJ | BAB31030.1 EMBL· GenBank· DDBJ | mRNA | ||
AK087982 EMBL· GenBank· DDBJ | BAC40074.1 EMBL· GenBank· DDBJ | mRNA | ||
BC058180 EMBL· GenBank· DDBJ | AAH58180.1 EMBL· GenBank· DDBJ | mRNA |