Human Gene RAD50 (ENST00000378823.8) from GENCODE V44
Description: Homo sapiens RAD50 double strand break repair protein (RAD50), mRNA. (from RefSeq NM_005732) RefSeq Summary (NM_005732): The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000378823.8 Gencode Gene: ENSG00000113522.14 Transcript (Including UTRs) Position: hg38 chr5:132,556,977-132,646,349 Size: 89,373 Total Exon Count: 25 Strand: + Coding Region Position: hg38 chr5:132,557,325-132,642,364 Size: 85,040 Coding Exon Count: 25
ID:RAD50_HUMAN DESCRIPTION: RecName: Full=DNA repair protein RAD50; Short=hRAD50; EC=3.6.-.-; 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. COFACTOR: Binds 1 zinc ion per homodimer (By similarity). SUBUNIT: 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. SUBCELLULAR LOCATION: Nucleus. Chromosome, telomere. Note=Localizes to discrete nuclear foci after treatment with genotoxic agents. TISSUE SPECIFICITY: Expressed at very low level in most tissues, except in testis where it is expressed at higher level. Expressed in fibroblasts. 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). PTM: Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity). DISEASE: Defects in RAD50 are the cause of Nijmegen breakage syndrome-like disorder (NBSLD) [MIM:613078]; also called NBS-like disorder or RAD50 deficiency. NBSLD is a disorder similar to Nijmegen breakage syndrome and characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, short stature and bird-like face. Immunodeficiency is absent. MISCELLANEOUS: In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells. SIMILARITY: Belongs to the SMC family. RAD50 subfamily. SIMILARITY: Contains 1 zinc-hook domain. SEQUENCE CAUTION: Sequence=AAH62603.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92878
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
DQ655928 - Homo sapiens clone UGL7g07, mRNA sequence. BC140005 - Homo sapiens RAD50 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:8860357), partial cds. U63139 - Homo sapiens Rad50 (Rad50) mRNA, complete cds. AK290597 - Homo sapiens cDNA FLJ75532 partial cds, highly similar to Homo sapiens RAD50 homolog (S. cerevisiae) (RAD50), transcript variant 1, mRNA. BC108282 - Homo sapiens RAD50 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:3855371), partial cds. JD217630 - Sequence 198654 from Patent EP1572962. AF057299 - Homo sapiens RAD50-2 protein (RAD50) mRNA, alternatively spliced, complete cds. AF057300 - Homo sapiens truncated RAD50 protein (RAD50) mRNA, complete cds. BC062603 - Homo sapiens RAD50 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:5493315), partial cds. BC073850 - Homo sapiens RAD50 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:4385515), partial cds. BC136436 - Homo sapiens RAD50 homolog (S. cerevisiae), mRNA (cDNA clone MGC:168048 IMAGE:9020425), complete cds. JD143188 - Sequence 124212 from Patent EP1572962. JD408686 - Sequence 389710 from Patent EP1572962. JD434843 - Sequence 415867 from Patent EP1572962. JD223751 - Sequence 204775 from Patent EP1572962. JD039046 - Sequence 20070 from Patent EP1572962. AK307439 - Homo sapiens cDNA, FLJ97387. JD256490 - Sequence 237514 from Patent EP1572962. JD476601 - Sequence 457625 from Patent EP1572962. JD058503 - Sequence 39527 from Patent EP1572962. JD351423 - Sequence 332447 from Patent EP1572962. Z75311 - H.sapiens mRNA for RAD50. JD300852 - Sequence 281876 from Patent EP1572962. JD359080 - Sequence 340104 from Patent EP1572962. JD121095 - Sequence 102119 from Patent EP1572962. JD039956 - Sequence 20980 from Patent EP1572962. JD512257 - Sequence 493281 from Patent EP1572962. JD363388 - Sequence 344412 from Patent EP1572962. JD464516 - Sequence 445540 from Patent EP1572962. JD455857 - Sequence 436881 from Patent EP1572962. JD328358 - Sequence 309382 from Patent EP1572962. JD272185 - Sequence 253209 from Patent EP1572962. JD153142 - Sequence 134166 from Patent EP1572962. JD127021 - Sequence 108045 from Patent EP1572962. JD415849 - Sequence 396873 from Patent EP1572962. JD411211 - Sequence 392235 from Patent EP1572962. JD325168 - Sequence 306192 from Patent EP1572962. JD119186 - Sequence 100210 from Patent EP1572962. JD491689 - Sequence 472713 from Patent EP1572962. JD061704 - Sequence 42728 from Patent EP1572962. JD047149 - Sequence 28173 from Patent EP1572962. JD351133 - Sequence 332157 from Patent EP1572962. JD396063 - Sequence 377087 from Patent EP1572962. JD355499 - Sequence 336523 from Patent EP1572962. JD044807 - Sequence 25831 from Patent EP1572962. JD166515 - Sequence 147539 from Patent EP1572962. JD087354 - Sequence 68378 from Patent EP1572962. JD285508 - Sequence 266532 from Patent EP1572962. JD115397 - Sequence 96421 from Patent EP1572962. JD220478 - Sequence 201502 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03440 - Homologous recombination hsa03450 - Non-homologous end-joining
BioCarta from NCI Cancer Genome Anatomy Project h_atmPathway - ATM Signaling Pathway h_atrbrcaPathway - Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility
Reactome (by CSHL, EBI, and GO)
Protein Q92878 (Reactome details) participates in the following event(s):
R-HSA-75172 Formation of RAD50:MRE11 complex R-HSA-75174 Association of RAD50:MRE11A complex with NBN (NBS1) via MRE11A interaction R-HSA-3785768 MRN complex binds DNA double strand breaks R-HSA-5682020 MRN complex binds shortened telomeres R-HSA-5687675 LIG3 ligates remaining SSBs in MMEJ R-HSA-5686410 BLM mediates dissolution of double Holliday junction R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693589 D-loop dissociation and strand annealing R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break R-HSA-5687465 MRN complex binds RBBP8 R-HSA-5693612 MRN complex bound to DNA ends recruits ATM R-HSA-5682018 MRN complex bound to shortened telomeres recruits ATM R-HSA-5685838 CX3 complex binds D-loop structures R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 R-HSA-5682044 KAT5 acetylates ATM at DNA DSBs R-HSA-5693540 MRN activates ATM R-HSA-5693598 ATM phosphorylates NBN R-HSA-5687464 MRN and RBBP8 resect DNA DSBs in MMEJ R-HSA-6792712 KAT5 acetylates ATM at shortened telomeres R-HSA-5682026 MRN bound to shortened telomeres activates ATM R-HSA-5687484 PARP1 or PARP2, FEN1 and POLQ are recruited to MMEJ site R-HSA-5687673 MRN recruits LIG3:XRCC1 to MMEJ sites R-HSA-5687664 FEN1 cleaves displaced ssDNA flaps during MMEJ R-HSA-5684081 MRN complex binds CDK2 and RBBP8 R-HSA-5693602 ATM recognizes H2AFX-Nucleosomes R-HSA-5684071 RNF4 ubiquitinates MDC1 R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop R-HSA-5687640 POLQ extends annealed 3'-ssDNA overhangs in MMEJ R-HSA-5687653 PARP1,PARP2 dimers bound to MMEJ sites autoPARylate R-HSA-5693583 MDC1 associates with gamma-H2AFX at nuclear foci R-HSA-5683967 EYA1-4 dephosphorylates tyrosine Y142 of H2AFX R-HSA-5683986 APBB1 and MAPK8 bind diphosphorylated H2AFX R-HSA-5693549 ATM phosphorylates histone H2AFX on S139 at DNA DSBs R-HSA-5684096 CDK2 phosphorylates RBBP8 R-HSA-5684140 ATM phosphorylates RBBP8 R-HSA-5693608 Initial resection of double-strand break ends R-HSA-5684108 BRCA1 binds phosphorylated RBBP8 R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment R-HSA-5682967 WHSC1 binds DNA DSBs R-HSA-5693536 ATM phosphorylates MDC1 R-HSA-5683964 ATM phosphorylates EYA1-4 R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-5682983 ATM phosphorylates WHSC1 R-HSA-5682965 WHSC1 dimethylates histone H4 on lysine K21 at DSBs R-HSA-5682992 KDM4A,B bind H4K20Me2 R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5682588 RNF8 binds phosphorylated MDC1 at DNA DSBs R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8 R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs R-HSA-5682863 RNF168 binds DNA DSBs R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs R-HSA-5683405 PPP5C dephosphorylates TP53BP1 R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-5682598 ATM phosphorylates HERC2 R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs R-HSA-5683735 CHEK2 is recruited to DNA DSBs R-HSA-5683801 CHEK2 phosphorylates BRCA1 R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM R-HSA-5684052 PIAS4 SUMOylates MDC1 R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM R-HSA-5686704 Activated ATM phosphorylates DCLRE1C R-HSA-5693548 Sensing of DNA Double Strand Breaks R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence R-HSA-5685939 HDR through MMEJ (alt-NHEJ) R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693606 DNA Double Strand Break Response R-HSA-2559583 Cellular Senescence R-HSA-5693538 Homology Directed Repair R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693537 Resolution of D-Loop Structures R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-912446 Meiotic recombination R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-2262752 Cellular responses to stress R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-73894 DNA Repair R-HSA-1500620 Meiosis R-HSA-8953897 Cellular responses to external stimuli R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-1474165 Reproduction R-HSA-1640170 Cell Cycle R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69481 G2/M Checkpoints R-HSA-5633007 Regulation of TP53 Activity R-HSA-69620 Cell Cycle Checkpoints R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
