RAP80

Summary

Gene Symbol: RAP80
Description: ubiquitin interaction motif containing 1
Alias: RAP80, X2HRIP110, BRCA1-A complex subunit RAP80, receptor-associated protein 80, retinoid X receptor-interacting protein 110
Species: human
Products:     RAP80

Top Publications

  1. Yan Z, Kim Y, Jetten A. RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor. J Biol Chem. 2002;277:32379-88 pubmed
    In this study, we describe the characterization of a novel nuclear protein, referred to as RAP80. The RAP80 cDNA was cloned from a human testis cDNA library and encodes a 719-amino acid protein containing two potential CX(2)CX(11)HX(3)C-..
  2. Wang B, Matsuoka S, Ballif B, Zhang D, Smogorzewska A, Gygi S, et al. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007;316:1194-8 pubmed
    ..Abraxas recruits the ubiquitin-interacting motif (UIM)-containing protein RAP80 to BRCA1...
  3. Kim H, Chen J, Yu X. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science. 2007;316:1202-5 pubmed
    ..We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans...
  4. Nikkilä J, Coleman K, Morrissey D, Pylkäs K, Erkko H, Messick T, et al. Familial breast cancer screening reveals an alteration in the RAP80 UIM domain that impairs DNA damage response function. Oncogene. 2009;28:1843-52 pubmed publisher
    ..Recently, a new BRCA1-interacting protein, receptor associated protein 80 (RAP80), was identified...
  5. Yan J, Kim Y, Yang X, Li L, Liao G, Xia F, et al. The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair response. Cancer Res. 2007;67:6647-56 pubmed
    In this study, we examine the potential role of receptor-associated protein 80 (RAP80), a nuclear protein containing two ubiquitin-interacting motifs (UIM), in DNA damage response and double-strand break (DSB) repair...
  6. Kim H, Huang J, Chen J. CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. Nat Struct Mol Biol. 2007;14:710-5 pubmed
    ..a crucial part in the DNA damage response through its interactions with many proteins, including BACH1, CtIP and RAP80. Here we identify a coiled-coil domain-containing protein, CCDC98, as a BRCA1-interacting protein...
  7. Feng L, Huang J, Chen J. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009;23:719-28 pubmed publisher
    ..the accumulation of BRCA1 at sites of DNA breaks, involves the ubiquitin-binding motif (UIM)-containing protein RAP80, a coiled-coil domain protein CCDC98/Abraxas, and a deubiquitinating enzyme BRCC36...
  8. Shao G, Patterson Fortin J, Messick T, Feng D, Shanbhag N, Wang Y, et al. MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks. Genes Dev. 2009;23:740-54 pubmed publisher
    b>Rap80 targets the breast cancer suppressor protein BRCA1 along with Abraxas and the BRCC36 deubiquitinating enzyme (DUB) to polyubiquitin structures at DNA double-strand breaks (DSBs)...
  9. Sobhian B, Shao G, Lilli D, Culhane A, Moreau L, Xia B, et al. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science. 2007;316:1198-202 pubmed
    ..We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein...

More Information

Publications99

  1. Liu Z, Wu J, Yu X. CCDC98 targets BRCA1 to DNA damage sites. Nat Struct Mol Biol. 2007;14:716-20 pubmed
    ..Recently, we have demonstrated that a ubiquitin-binding protein, RAP80, is required for DNA damage-induced BRCA1 translocation...
  2. Wang B, Hurov K, Hofmann K, Elledge S. NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev. 2009;23:729-39 pubmed publisher
    ..analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE...
  3. Wang B, Elledge S. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci U S A. 2007;104:20759-63 pubmed
    The Brca1 A complex contains Brca1/Bard1, Abraxas, Rap80, and Brcc36; however, with the exception of the Brca1-Abraxas interaction, how the A complex is assembled is not known...
  4. Akbari M, Ghadirian P, Robidoux A, Foumani M, Sun Y, Royer R, et al. Germline RAP80 mutations and susceptibility to breast cancer. Breast Cancer Res Treat. 2009;113:377-81 pubmed publisher
    ..b>RAP80 works upstream of BRCA1 and is essential for the localization of BRCA1 to the site of damaged DNA...
  5. He C, Kraft P, Chen C, Buring J, Pare G, Hankinson S, et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat Genet. 2009;41:724-8 pubmed publisher
    ..42 (in or near the gene BRSK1), 5q35.2 (in or near genes UIMC1 and HK3) and 6p24.2 (in the gene SYCP2L). These newly identified loci might expand understanding of the biological pathways regulating these two traits. ..
  6. Helchowski C, Skow L, Roberts K, Chute C, Canman C. A small ubiquitin binding domain inhibits ubiquitin-dependent protein recruitment to DNA repair foci. Cell Cycle. 2013;12:3749-58 pubmed publisher
    ..isolated RAD18 UBD interfered with 53BP1 chromatin spreading, as well as other important DDR mediators, including RAP80 and the BRCA1 tumor suppressor protein, consistent with the model that the RAD18 UBD is blocking access of ..
  7. Wu W, Togashi Y, Johmura Y, Miyoshi Y, Nobuoka S, Nakanishi M, et al. HP1 regulates the localization of FANCJ at sites of DNA double-strand breaks. Cancer Sci. 2016;107:1406-1415 pubmed publisher
    ..exclusive complexes with Fanconi anemia group J protein (FANCJ, also called BACH1 or BRIP1), CtIP, and Abraxas/RAP80 through its BRCA1 C terminus (BRCT) domains, while its RING domain binds to BRCA1-associated RING domain 1 (BARD1)...
  8. Jin G, Mao X, Qiao Z, Chen B, Jin F. RAP80 expression in breast cancer and its relationship with apoptosis in breast cancer cells. Onco Targets Ther. 2019;12:625-634 pubmed publisher
    b>RAP80 is a member of BRCA1-A complex, which plays an important role in regulating the cell cycle checkpoint and DNA damage repair in the nucleus...
  9. Carty C, Spencer K, Setiawan V, Fernández Rhodes L, Malinowski J, Buyske S, et al. Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study. Hum Reprod. 2013;28:1695-706 pubmed publisher
    ..Such data will be increasingly important for prioritizing GWAS SNPs for follow-up in fine-mapping and resequencing studies, as well as in translational research. ..
  10. Ismail H, Didangelos A, Vincent T, Saklatvala J. Rapid Activation of Transforming Growth Factor ?-Activated Kinase 1 in Chondrocytes by Phosphorylation and K63 -Linked Polyubiquitination Upon Injury to Animal Articular Cartilage. Arthritis Rheumatol. 2017;69:565-575 pubmed publisher
    ..b>Receptor associated protein 80 (RAP-80) ubiquitin interacting motif agarose was used in a pull-down assay to obtain K63 -..
  11. Romeo M, Karachaliou N, Chaid I, Queralt C, de Aguirre I, Del Carmen Gómez M, et al. Low RAP80 mRNA expression correlates with shorter survival in sporadic high-grade serous ovarian carcinoma. Int J Biol Markers. 2017;32:e90-e95 pubmed publisher
    ..Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR-pathway-related gene that influences BRCA1 activity...
  12. Yin Z, Menendez D, Resnick M, French J, Janardhan K, Jetten A. RAP80 is critical in maintaining genomic stability and suppressing tumor development. Cancer Res. 2012;72:5080-90 pubmed publisher
    The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (..
  13. Zhang L, Wang Z, Shi R, Zhu X, Zhou J, Peng B, et al. RNF126 Quenches RNF168 Function in the DNA Damage Response. Genomics Proteomics Bioinformatics. 2018;16:428-438 pubmed publisher
    ..focus formation of total ubiquitin FK2, TP53-binding protein 1 (53BP1), and receptor-associated protein 80 (RAP80)...
  14. Osorio A, Barroso A, Garcia M, Martinez Delgado B, Urioste M, Benitez J. Evaluation of the BRCA1 interacting genes RAP80 and CCDC98 in familial breast cancer susceptibility. Breast Cancer Res Treat. 2009;113:371-6 pubmed publisher
    b>RAP80 and CCDC98 have arisen as new candidate breast cancer susceptibility genes, since they encode for two very recently identified BRCA1 interacting proteins...
  15. Watanabe S, Iimori M, Chan D, Hara E, Kitao H, Maehara Y. MDC1 methylation mediated by lysine methyltransferases EHMT1 and EHMT2 regulates active ATM accumulation flanking DNA damage sites. Sci Rep. 2018;8:10888 pubmed publisher
    ..g. 53BP1 and RAP80, at the DSB sites...
  16. Baranes Bachar K, Levy Barda A, Oehler J, Reid D, Soria Bretones I, Voss T, et al. The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair. Mol Cell. 2018;69:866-878.e7 pubmed publisher
    ..This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites...
  17. Zeqiraj E, Tian L, Piggott C, Pillon M, Duffy N, Ceccarelli D, et al. Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function. Mol Cell. 2015;59:970-83 pubmed publisher
    ..of heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHMT2 and RAP80. These data provide an explanation of how an inactive pseudo DUB allosterically activates a cognate DUB partner ..
  18. Lee B, Singh A, Mark Glover J, Hendzel M, Spyracopoulos L. Molecular Basis for K63-Linked Ubiquitination Processes in Double-Strand DNA Break Repair: A Focus on Kinetics and Dynamics. J Mol Biol. 2017;429:3409-3429 pubmed publisher
    ..BRCC36, and the proteasome, and through the binding of chains by recognition modules on repair proteins such as RAP80. We highlight a number of aspects regarding our current understanding for the role of kinetics and dynamics in ..
  19. Ling H, Li S, Wu Y, Zheng Y, Qiao F, Yao L, et al. Genetic evaluation of BRCA1 associated a complex genes with triple-negative breast cancer susceptibility in Chinese women. Oncotarget. 2016;7:9759-72 pubmed publisher
    ..We detected 37 common variants in ABRAXAS, RAP80, BRE, BRCC36 and NBA1/MERIT40 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the ..
  20. Feng L, Wang J, Chen J. The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. 2010;285:30982-8 pubmed publisher
    ..We and others showed previously that BRCC36 is a component of the BRCA1-A complex, which consists of RAP80, CCDC98/ABRAXAS, BRCC45/BRE, MERIT40/NBA1, BRCC36, and BRCA1...
  21. Goldstein M, Kastan M. Repair versus Checkpoint Functions of BRCA1 Are Differentially Regulated by Site of Chromatin Binding. Cancer Res. 2015;75:2699-707 pubmed publisher
    ..Prior reports demonstrated that BRCA1 recruitment to areas of DNA breakage depended on RAP80 and the RNF8/RNF168 E3 ubiquitin ligases...
  22. Typas D, Luijsterburg M, Wiegant W, Diakatou M, Helfricht A, Thijssen P, et al. The de-ubiquitylating enzymes USP26 and USP37 regulate homologous recombination by counteracting RAP80. Nucleic Acids Res. 2015;43:6919-33 pubmed publisher
    ..cascade involving the E3 ubiquitin ligases RNF8/RNF168 and the ubiquitin-dependent assembly of the BRCA1-Abraxas-RAP80-MERIT40 complex...
  23. Gatti M, Pinato S, Maiolica A, Rocchio F, Prato M, Aebersold R, et al. RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage. Cell Rep. 2015;10:226-38 pubmed publisher
    ..activation of the DNA damage response (DDR) and is directly recognized by crucial DDR mediators, namely 53BP1, Rap80, RNF168, and RNF169...
  24. Kim G, Oh G, Yoon J, Lee G, Lee K, Kim S. Hepatic TRAP80 selectively regulates lipogenic activity of liver X receptor. J Clin Invest. 2015;125:183-93 pubmed publisher
    ..Moreover, targeting the interaction between TRAP80 and LXR should facilitate the development of potential LXR agonists that effectively prevent atherosclerosis. ..
  25. Rozenova K, Jiang J, Donaghy R, Aressy B, Greenberg R, Tong W. MERIT40 deficiency expands hematopoietic stem cell pools by regulating thrombopoietin receptor signaling. Blood. 2015;125:1730-8 pubmed publisher
    ..Here, we show that MERIT40 (Mediator of RAP80 Interactions and Targeting 40 kDa [M40]), a core subunit of an Lnk-associated Lys63 deubiquitinating (DUB) complex,..
  26. Yang Q, Lin W, Liu Z, Zhu J, Huang N, Cui Z, et al. RAP80 is an independent prognosis biomarker for the outcome of patients with esophageal squamous cell carcinoma. Cell Death Dis. 2018;9:146 pubmed publisher
    ..b>RAP80/UIMC1 (ubiquitin interaction motif containing 1), one of those DDR factors we tested, was highly overexpressed in ..
  27. Chung H, Korm S, Lee S, Phorl S, Noh S, Han M, et al. RAP80 binds p32 to preserve the functional integrity of mitochondria. Biochem Biophys Res Commun. 2017;492:441-446 pubmed publisher
    b>RAP80, a member of the BRCA1-A complex, is a well-known crucial regulator of cell cycle checkpoint and DNA damage repair in the nucleus...
  28. Cirauqui B, Margeli M, Quiroga V, Quer A, Karachaliou N, Chaib I, et al. DNA repair pathways to regulate response to chemoradiotherapy in patients with locally advanced head and neck cancer. Tumour Biol. 2016;37:13435-13443 pubmed
    ..We assessed mRNA expression levels of DNA repair-related genes BRCA1, RAP80, 53 binding protein 1 (53BP1), mediator of DNA damage checkpoint 1 (MDC1), and RNF8...
  29. Li Y, Luo K, Yin Y, Wu C, Deng M, Li L, et al. USP13 regulates the RAP80-BRCA1 complex dependent DNA damage response. Nat Commun. 2017;8:15752 pubmed publisher
    ..Receptor-associated protein 80 (RAP80) helps recruit BRCA1 to double-strand breaks (DSBs) through the scaffold protein CCDC98 (Abraxas) and facilitates ..
  30. Tryfonidis K, Papadaki C, Assele S, Lagoudaki E, Menis J, Koutsopoulos A, et al. Association of BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression levels between primary tumors and infiltrated regional lymph nodes in patients with resectable non-small cell lung cancer. Pharmacogenomics J. 2019;19:15-24 pubmed publisher
    ..with matched PT and LNs samples)-case and 56 PT only samples-control cohorts] were analyzed for BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression by quantitative real-time polymerase-chain reaction (PCR)...
  31. Moran T, Wei J, Cobo M, Qian X, Domine M, Zou Z, et al. Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies. Ann Oncol. 2014;25:2147-55 pubmed publisher
    In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC)...
  32. Leung J, Makharashvili N, Agarwal P, Chiu L, Pourpre R, Cammarata M, et al. ZMYM3 regulates BRCA1 localization at damaged chromatin to promote DNA repair. Genes Dev. 2017;31:260-274 pubmed publisher
    ..to damaged chromatin through specific interactions with components of the BRCA1-A subcomplex, including ABRA1 and RAP80. By regulating ABRA1 recruitment to damaged chromatin, ZMYM3 facilitates the fine-tuning of BRCA1 interactions ..
  33. Nakada S. Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice. J Radiat Res. 2016;57 Suppl 1:i33-i40 pubmed publisher
    ..The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair...
  34. Zhu B, Yan K, Li L, Lin M, Zhang S, He Q, et al. K63-linked ubiquitination of FANCG is required for its association with the Rap80-BRCA1 complex to modulate homologous recombination repair of DNA interstand crosslinks. Oncogene. 2015;34:2867-78 pubmed publisher
    ..that FANCG K63Ub was dispensable for monoubiquitination of FANCD2, but was required for FANCG to interact with the Rap80-BRCA1 (receptor-associated protein 80-BRCA1) complex for subsequent modulation of HR repair of ICLs induced by ..
  35. Jiang Q, Paramasivam M, Aressy B, Wu J, Bellani M, Tong W, et al. MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links. Genes Dev. 2015;29:1955-68 pubmed publisher
    MERIT40 is an essential component of the RAP80 ubiquitin recognition complex that targets BRCA1 to DNA damage sites...
  36. Wang Y, Zhang N, Zhang L, Li R, Fu W, Ma K, et al. Autophagy Regulates Chromatin Ubiquitination in DNA Damage Response through Elimination of SQSTM1/p62. Mol Cell. 2016;63:34-48 pubmed publisher
    ..As a result, DNA repair proteins such as BRCA1, RAP80, and Rad51 cannot be recruited to the sites of DNA double-strand breaks (DSBs), which impairs DSB repair...
  37. Her J, Soo Lee N, Kim Y, Kim H. Factors forming the BRCA1-A complex orchestrate BRCA1 recruitment to the sites of DNA damage. Acta Biochim Biophys Sin (Shanghai). 2016;48:658-64 pubmed publisher
    ..Factors comprising the BRCA1-A include RAP80, CCDC98/Abraxas, BRCC36, BRCC45, BARD1, BRCA1, and MERIT40, a RAP80-associated factor...
  38. An L, Jiang Y, Ng H, Man E, Chen J, Khoo U, et al. Dual-utility NLS drives RNF169-dependent DNA damage responses. Proc Natl Acad Sci U S A. 2017;114:E2872-E2881 pubmed publisher
    Loading of p53-binding protein 1 (53BP1) and receptor-associated protein 80 (RAP80) at DNA double-strand breaks (DSBs) drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA repair...
  39. Lombardi P, Matunis M, Wolberger C. RAP80, ubiquitin and SUMO in the DNA damage response. J Mol Med (Berl). 2017;95:799-807 pubmed publisher
    A decade has passed since the first reported connection between RAP80 and BRCA1 in DNA double-strand break repair...
  40. Kozlov S, Waardenberg A, Engholm Keller K, Arthur J, Graham M, Lavin M. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen. Mol Cell Proteomics. 2016;15:1032-47 pubmed publisher
    ..Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins ..
  41. Zhen N, Yang Q, Wu Q, Zhu X, Wang Y, Sun F, et al. A novelly synthesized phenanthroline derivative is a promising DNA-damaging anticancer agent inhibiting G1/S checkpoint transition and inducing cell apoptosis in cancer cells. Cancer Chemother Pharmacol. 2016;77:169-80 pubmed publisher
    ..apoptosis by not only activating ATM/CHK1 signaling pathway, but also targeting CHK1 to reduce the expression of RAP80 and PARP-1 to compromise the DNA damage repair in tumor cells...
  42. Sharma V, Khurana S, Kubben N, Abdelmohsen K, Oberdoerffer P, Gorospe M, et al. A BRCA1-interacting lncRNA regulates homologous recombination. EMBO Rep. 2015;16:1520-34 pubmed publisher
    ..The HR defect in the absence of DDSR1 is marked by aberrant accumulation of BRCA1 and RAP80 at DSB sites...
  43. Patterson Fortin J, Shao G, Bretscher H, Messick T, Greenberg R. Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. J Biol Chem. 2010;285:30971-81 pubmed publisher
    ..deubiquitinating enzyme (DUB) and a member of two protein complexes: the DNA damage-responsive BRCA1-RAP80 complex, and the cytoplasmic BRCC36 isopeptidase complex (BRISC)...
  44. Mikawa S, Morozumi T, Shimanuki S, Hayashi T, Uenishi H, Domukai M, et al. Fine mapping of a swine quantitative trait locus for number of vertebrae and analysis of an orphan nuclear receptor, germ cell nuclear factor (NR6A1). Genome Res. 2007;17:586-93 pubmed
    ..substitution altered the binding activity of NR6A1 to its corepressors, nuclear receptor-associated protein 80 (RAP80) and nuclear receptor corepressor 1 (NCOR1)...
  45. Guzzo C, Berndsen C, Zhu J, Gupta V, Datta A, Greenberg R, et al. RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage. Sci Signal. 2012;5:ra88 pubmed publisher
    The DNA repair function of the breast cancer susceptibility protein BRCA1 depends in part on its interaction with RAP80, which targets BRCA1 to DNA double-strand breaks (DSBs) through recognition of K63-linked polyubiquitin chains...
  46. Yan J, Jetten A. RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites. Cancer Lett. 2008;271:179-90 pubmed publisher
    ..proteins are recruited to DNA damage foci and revealed key roles for the receptor-associated protein 80 (RAP80) and the E3 ligase RNF8 in this process...
  47. Shao G, Lilli D, Patterson Fortin J, Coleman K, Morrissey D, Greenberg R. The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc Natl Acad Sci U S A. 2009;106:3166-71 pubmed publisher
    ..Inhibition of the Rap80-BRCC36 de-ubiquitinating enzyme complex partially restored DSB-associated ubiquitin levels following RNF8 ..
  48. Sato Y, Yoshikawa A, Mimura H, Yamashita M, Yamagata A, Fukai S. Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80. EMBO J. 2009;28:2461-8 pubmed publisher
    b>RAP80 has a key role in the recruitment of the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA-damage foci for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs (UIMs)..
  49. Soo Lee N, Jin Chung H, Kim H, Yun Lee S, Ji J, Seo Y, et al. TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage. Nat Commun. 2016;7:10463 pubmed publisher
    b>RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions...
  50. Kensche T, Tokunaga F, Ikeda F, Goto E, Iwai K, Dikic I. Analysis of nuclear factor-?B (NF-?B) essential modulator (NEMO) binding to linear and lysine-linked ubiquitin chains and its role in the activation of NF-?B. J Biol Chem. 2012;287:23626-34 pubmed publisher
    ..This phenomenon could explain quantitatively distinct NF-?B activation patterns in response to numerous cell stimuli. ..
  51. Cho H, Lee S, Kim H. The linker connecting the tandem ubiquitin binding domains of RAP80 is critical for lysine 63-linked polyubiquitin-dependent binding activity. BMB Rep. 2009;42:764-8 pubmed
    The tandem ubiquitin-interacting motif (UIM) domain located at the N-terminus of Receptor Associated Protein 80 (RAP80) plays a crucial role in ionizing radiation (IR)-induced DNA damage response...
  52. Markin C, Xiao W, Spyracopoulos L. Mechanism for recognition of polyubiquitin chains: balancing affinity through interplay between multivalent binding and dynamics. J Am Chem Soc. 2010;132:11247-58 pubmed publisher
    b>RAP80 plays a key role in signal transduction in the DNA damage response by recruiting proteins to DNA damage foci by binding K63-polyubiquitin chains with two tandem ubiquitin-interacting motifs (tUIM)...
  53. Kim Y, Nakanishi G, Oudes A, Kim K, Wang H, Kilpatrick D, et al. Tsp57: a novel gene induced during a specific stage of spermatogenesis. Biol Reprod. 2004;70:106-13 pubmed
    Recently, we described the identification of a novel protein, nuclear receptor-associated protein 80 (RAP80), which is highly expressed in spermatocytes and appears to have a role in regulating gene expression...
  54. Sekiyama N, Jee J, Isogai S, Akagi K, Huang T, Ariyoshi M, et al. NMR analysis of Lys63-linked polyubiquitin recognition by the tandem ubiquitin-interacting motifs of Rap80. J Biomol NMR. 2012;52:339-50 pubmed publisher
    ..The Lys63-linked polyubiquitin chain is recognized by tandem ubiquitin-interacting motifs (tUIMs) of Rap80 for the regulation of DNA repair...
  55. Yan J, Menendez D, Yang X, Resnick M, Jetten A. A regulatory loop composed of RAP80-HDM2-p53 provides RAP80-enhanced p53 degradation by HDM2 in response to DNA damage. J Biol Chem. 2009;284:19280-9 pubmed publisher
    The ubiquitin interaction motif-containing protein RAP80 plays a key role in DNA damage response signaling...
  56. Rosell R, Perez Roca L, Sanchez J, Cobo M, Moran T, Chaib I, et al. Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression. PLoS ONE. 2009;4:e5133 pubmed publisher
    ..b>RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1...
  57. Strauss C, Halevy T, Macarov M, Argaman L, Goldberg M. MDC1 is ubiquitylated on its tandem BRCT domain and directly binds RAP80 in a UBC13-dependent manner. DNA Repair (Amst). 2011;10:806-14 pubmed publisher
    ..Here we demonstrate that MDC1 binds directly to RAP80, which is a DNA damage response protein that recruits BRCA1 to sites of damage...
  58. Solyom S, Aressy B, Pylkäs K, Patterson Fortin J, Hartikainen J, Kallioniemi A, et al. Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions. Sci Transl Med. 2012;4:122ra23 pubmed publisher
    ..1082G>A mutation connects to cancer predisposition. These findings contribute to the concept of a BRCA-centered tumor suppressor network and provide the identity of Abraxas as a new breast cancer susceptibility gene. ..
  59. Hu Y, Scully R, Sobhian B, Xie A, Shestakova E, Livingston D. RAP80-directed tuning of BRCA1 homologous recombination function at ionizing radiation-induced nuclear foci. Genes Dev. 2011;25:685-700 pubmed publisher
    ..Polyubiquitin binding by one of these structures, the RAP80/BRCA1 complex, is required for efficient BRCA1 focal recruitment, but the relationship of this process to the ..
  60. Castaneda C, Kashyap T, Nakasone M, Krueger S, Fushman D. Unique structural, dynamical, and functional properties of k11-linked polyubiquitin chains. Structure. 2013;21:1168-81 pubmed publisher
    ..Our data support the hypothesis that polyubiquitin chains of different linkages possess unique conformational and dynamical properties, allowing them to be recognized differently by downstream receptor proteins. ..
  61. Wu J, Huen M, Lu L, Ye L, Dou Y, Ljungman M, et al. Histone ubiquitination associates with BRCA1-dependent DNA damage response. Mol Cell Biol. 2009;29:849-60 pubmed publisher
    ..However, the molecular mechanisms involved are not clear. Here, we have identified that RAP80/UIMC1 (ubiquitin interaction motif containing 1), a functional partner of BRCA1, recognizes ubiquitinated histones ..
  62. Novak D, Sabbaghian N, Maillet P, Chappuis P, Foulkes W, Tischkowitz M. Analysis of the genes coding for the BRCA1-interacting proteins, RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic breast cancer cases. Breast Cancer Res Treat. 2009;117:453-9 pubmed publisher
    ..Two such genes, RAP80 and Abraxas, have recently been identified to be in a complex with BRCA1, and are required for the localization of ..
  63. Sims J, Cohen R. Linkage-specific avidity defines the lysine 63-linked polyubiquitin-binding preference of rap80. Mol Cell. 2009;33:775-83 pubmed publisher
    ..Our model is human Rap80, which contains tandem ubiquitin interacting motifs (UIMs) that bind to K63-polyUb at DNA double-strand breaks...
  64. Nakasone M, Livnat Levanon N, Glickman M, Cohen R, Fushman D. Mixed-linkage ubiquitin chains send mixed messages. Structure. 2013;21:727-40 pubmed publisher
    ..Linkage-selective receptors from hHR23A and Rap80 preferentially bound to the K48 or K63 linkages in the branched trimer...
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    ..Thus, FA pathway loss-of-function results in accumulation of 53BP1, RIF1 and RAP80 at damaged chromatin, which impair DNA resection at stalled replication fork-associated DNA breaks and impede HR...
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    ..Intriguingly, YFP-BRCA1 displayed significantly better focal co-localization with BARD1, RAP80 and Abraxas than with the upstream foci-initiating proteins gamma H2AX and MDC1...
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    ..Together, these studies reveal critical interactions required for the formation and function of BRCC36-containing DUB complexes. ..
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    ..We show that RNF168, its paralog RNF169, RAD18, and the BRCA1-interacting RAP80 protein accumulate at DSB sites through the use of bipartite modules composed of UBDs juxtaposed to peptide motifs ..
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    ..The Ub-interacting motif (UIM) domain of Rap80, which is a component of the BRCA1-A complex, interacts with Ub Lys-63 linkage conjugates and mediates the ..
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    b>RAP80, a nuclear protein with two functional ubiquitin-interaction motifs (UIMs) at its N-terminus, plays a critical role in the regulation of estrogen receptor alpha and DNA damage response signaling...
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    ..All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR...
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    We have identified RAP80/UIMC1, the protein highly expressed in testis, as a new cancer-associated antigen. Sera from 5% to 10% of patients with different types of cancer contain specific antibodies to RAP80/UIMC1...
  73. Yan J, Kim Y, Yang X, Albers M, Koegl M, Jetten A. Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alpha. Nucleic Acids Res. 2007;35:1673-86 pubmed
    In this study, we demonstrate that receptor-associated protein 80 (RAP80) interacts with estrogen receptor alpha (ERalpha) in an agonist-dependent manner...
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    ..Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause. ..
  75. Strauss C, Goldberg M. Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80. Cell Cycle. 2011;10:2850-7 pubmed
    ..Recently, we demonstrated that the key DDR protein MDC1 directly binds RAP80, an additional DDR protein that recruits BRCA1 to DSBs...
  76. Cho H, Lee E, Han S, Chung H, Jeong J, Kwon J, et al. Degradation of human RAP80 is cell cycle regulated by Cdc20 and Cdh1 ubiquitin ligases. Mol Cancer Res. 2012;10:615-25 pubmed publisher
    Receptor-associated protein 80 (RAP80) is a component of the BRCA1-A complex that recruits BRCA1 to DNA damage sites in the DNA damage-induced ubiquitin signaling pathway...
  77. Bian C, Wu R, CHO K, Yu X. Loss of BRCA1-A complex function in RAP80 null tumor cells. PLoS ONE. 2012;7:e40406 pubmed publisher
    b>Receptor Associated Protein 80 (RAP80) is a subunit of the BRCA1-A complex and targets BRCA1 to DNA damage sites in response to DNA double strand breaks...
  78. Hu Y, Petit S, Ficarro S, Toomire K, Xie A, Lim E, et al. PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination-mediated DNA repair. Cancer Discov. 2014;4:1430-47 pubmed publisher
    ..We previously found that BRCA1 HRR function is regulated by the RAP80 complex, but the mechanism was unclear...
  79. Anamika -, Markin C, Rout M, Spyracopoulos L. Molecular basis for impaired DNA damage response function associated with the RAP80 ΔE81 defect. J Biol Chem. 2014;289:12852-62 pubmed publisher
    ..The protein RAP80 plays a central role in the damage response by targeting BRCA1/BRCA2 tumor suppressors to DNA damage foci through ..
  80. Thach T, Lee N, Shin D, Han S, Kim G, Kim H, et al. Molecular determinants of polyubiquitin recognition by continuous ubiquitin-binding domains of Rad18. Biochemistry. 2015;54:2136-48 pubmed publisher
    ..Finally, we reveal that the ubiquitin-binding domains of Rad18 bind linear Ub2 more tightly than those of RAP80, providing a quantitative basis for blockage of RAP80 at DSB sites...
  81. Yan J, Yang X, Kim Y, Jetten A. RAP80 responds to DNA damage induced by both ionizing radiation and UV irradiation and is phosphorylated at Ser 205. Cancer Res. 2008;68:4269-76 pubmed publisher
    Receptor-associated protein (RAP80), a nuclear protein containing two ubiquitin-interacting motifs (UIM), was recently found to be associated with breast cancer-1 (BRCA1) and to translocate to ionizing radiation-induced foci (IRIF)...
  82. Park S, Korm S, Chung H, Choi S, Jang J, Cho S, et al. RAP80 regulates epithelial-mesenchymal transition related with metastasis and malignancy of cancer. Cancer Sci. 2016;107:267-73 pubmed publisher
    ..Here, we showed that EMT is induced by the downregulation of RAP80, a well-known regulator for DNA damage response...
  83. Coleman K, Greenberg R. The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection. J Biol Chem. 2011;286:13669-80 pubmed publisher
    ..The most recently discovered BRCA1-RAP80 complex is recruited to ubiquitin structures on chromatin surrounding the break...
  84. Cho H, Oh Y, Han S, Chung H, Kim C, Lee N, et al. Cdk1 protein-mediated phosphorylation of receptor-associated protein 80 (RAP80) serine 677 modulates DNA damage-induced G2/M checkpoint and cell survival. J Biol Chem. 2013;288:3768-76 pubmed publisher
    ..b>RAP80, a component of the BRCA1-A complex, is crucial in cell cycle checkpoint activation and DNA damage repair...
  85. Tikoo S, Madhavan V, Hussain M, Miller E, Arora P, Zlatanou A, et al. Ubiquitin-dependent recruitment of the Bloom syndrome helicase upon replication stress is required to suppress homologous recombination. EMBO J. 2013;32:1778-92 pubmed publisher
    ..ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80. Furthermore, we show that this mechanism of BLM relocalization is essential for BLM's ability to suppress ..
  86. Lee N, Chang H, Kim S, Ji J, Lee J, Lee H, et al. Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation. J Biol Chem. 2018;293:588-598 pubmed publisher
    ..RNF126 overexpression abolishes not only the formation of 53BP1 iRIF but also of RNF168, FK2, RAP80, and BRCA1...
  87. Wilson M, Harreman M, Taschner M, Reid J, Walker J, Erdjument Bromage H, et al. Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress. Cell. 2013;154:983-995 pubmed publisher
    ..Together, these results outline the multistep mechanism of Rpb1 polyubiquitylation triggered by transcription stress and uncover the key role played by Def1 as a facilitator of Elongin-Cullin ubiquitin ligase function. ..
  88. Johnson N, Johnson S, Yao W, Li Y, Choi Y, Bernhardy A, et al. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Proc Natl Acad Sci U S A. 2013;110:17041-6 pubmed publisher
    ..These results provide evidence for a two-event mechanism by which BRCA1-mutant tumors acquire anticancer therapy resistance. ..
  89. Anamika -, Spyracopoulos L. Molecular Basis for Phosphorylation-dependent SUMO Recognition by the DNA Repair Protein RAP80. J Biol Chem. 2016;291:4417-28 pubmed publisher
    ..b>RAP80 is a component of the BRCA1 A complex, and plays a key role in the recruitment process through the binding of Lys(..
  90. Bick G, Zhang F, Meetei A, Andreassen P. Coordination of the recruitment of the FANCD2 and PALB2 Fanconi anemia proteins by an ubiquitin signaling network. Chromosoma. 2017;126:417-430 pubmed publisher
    ..Interestingly, we find that the RNF8 partner, MDC1, as well as the ubiquitin-binding protein, RAP80, specifically recruit PALB2, while a different ubiquitin-binding protein, FAAP20, functions only in the ..