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FLASH GENE
Symbol TP53BP1 contributors: mct/ - updated : 03-11-2016
HGNC name tumor protein p53 binding protein 1
HGNC id 11999
Location 15q15.3      Physical location : 43.699.412 - 43.802.707
Synonym name
  • tumor suppressor p53-binding protein 1
  • p53-binding protein 1
  • Synonym symbol(s) 53BP1, FLJ41424, MGC138366, p202, p53BP1
    DNA
    TYPE functioning gene
    STRUCTURE 103.33 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    28 - 6210 - 1975 in all tissues except lung and liver 1994 8016121
    28 - 6236 - 1972 in all tissues except in lung and liver 1994 8016121
    28 - 6266 - 1977 - 2007 17940005
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, G1
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two BRCT domains
  • tandem Tudor domains, involved in the end joining and end protection functions , that is paramount for its localization to dysfunctional telomeres, but even without the full engagement of this domain, TP53BP1 has some ability to promote NHEJ of dysfunctional telomeres
  • a glycine- and arginine-rich (GAR) motif methylated by protein arginine N-methyltransferase 1
  • HOMOLOGY
    interspecies homolog to murine Tp53bp1
    homolog to C.elegans c09d8.1
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleoplasm,nuclear bodies
    text
  • colocalizes with TP53BP1 at sites of DNA double-strand breaks (DSBs), but only in the G1-phase of the cell cycle
  • TP53BP1 nuclear bodies shield chromosomal fragile sites sequestered in these compartments against erosion
  • basic FUNCTION
  • playing a role in p53-related signal transduction pathway
  • enhancing TP53-mediated transcriptional activation
  • having a role in the G2/M and the intra-S phase checkpoints
  • may play a separate role during mitosis; it was shown to be phosphorylated in mitotic cells and to be loaded onto kinetochores in prophase until mid-anaphase
  • having a role during mitosis or in the mitotic spindle assembly checkpoint
  • seems to have distinct and independent roles in response to genotoxic stress
  • with others ATM signalling mediator proteins, RNF8, RNF168 and MDC1 are also required for heterochromatic DSB repair
  • main facilitator of nonhomologous end joining (NHEJ) during the S phase of the cell cycle, beyond highly specialized lymphocyte rearrangements
  • inhibits homologous recombination in BRCA1-deficient cells by blocking resection of DNA breaks
  • TP53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress
  • unique function for TP53BP1 in end-joining and tumor suppression
  • in addition to end joining, TP53BP1 and NHEJ1 have overlapping functions in tumor suppression
  • is also present at dysfunctional telomeres, is a target of ATM that accumulates at DNA double-strand breaks and favors nonhomologous end-joining (NHEJ) repair over ATM-dependent resection and homology-directed repair
  • tripartite regulation of homologous recombination by RNF8, BRCA1, and TP53BP1
  • RNF168 and TP53BP1 have a similar influence on homologous recombination (HR) and also indicate that these factors may function in the same pathway to inhibit HR
  • RIF1 and TP53BP1 cooperate to block DSB resection to promote NHEJ in G1, which is antagonized by BRCA1 in S phase to ensure a switch of DSB repair mode to homologous recombination
  • requirement in mediating NHEJ at dysfunctional telomeres and in class switch recombination are not identical
  • protects telomeres lacking TERF2 from aberrant 5prime end resection
  • BRCA1 and TP53BP1 play decisive roles in the choice of DNA double-strand break repair mechanisms
  • role for TP53BP1 in regulating RB1 tumor suppressor activity
  • PAXIP1 status correlates with breast cancer staging, in a manner similar to what has been characterized for TP53BP1
  • unique role for TP53BP1 in replication fork stability
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • pathway involving gammaH2AX–MDC1–WHSC1 regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates TP53BP1 recruitment
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • central domain of wildtype TP53
  • interact with MDC1 directly through the tandem BRCT domain of MDC1 and AAs 1288–1409 of TP53BP1 (interaction playing a role in the regulation of mitosis)
  • interacting with RAD18 (RAD18 promotes TP53BP1-directed DSB repair by enhancing retention of TP53BP1, possibly through an interaction between RAD18 and TP53BP1 and the modification of TP53BP1)
  • interacting with RNF8 and PAXIP1 (RNF8 controls DNA damage-induced nuclear foci formation of PAXIP1, which in turn regulates TP53BP1 localization to the DNA damage sites)
  • interacting with TRIM28 (phosphorylation is critical for TP53BP1-mediated repair, overall phosphorylated TRIM28 levels are only modestly affected by TP53BP1 loss)
  • WHSC1 is an upstream regulator of TP53BP1 (methylates H4K20 at DSBs, which facilitates the subsequent accumulation of TP53BP1)
  • role for the cysteine protease Cathepsin L (CTSL) in the degradation of TP53BP1
  • TP53BP1 is imported to the nucleus through the NUP153-KPNB1 interplay
  • BRCA1 antagonises TP53BP1-dependent DNA repair in S phase by inhibiting its interaction with chromatin proximal to damage sites
  • RNF8 regulates BRCA1-independent homologous recombination in TP53BP1-depleted cells
  • colocalizes with TP53BP1, a key DNA damage response protein, and with other factors involved in DNA repair
  • RIF1 is an important contributor to the control of DSB repair by TP53BP1
  • RIF1 translocates to damage sites via ATM-dependent TP53BP1 phosphorylation
  • TP53BP1 promotes productive class switch recombination (CSR) and suppresses mutagenic DNA repair through distinct phosphodependent interactions with RIF1 and PAXIP1
  • RNF168 plays a central role in the regulation of TP53BP1 functions
  • TP53BP1 recruitment requires the direct recognition of a DSB-specific histone code and its influence on pathway choice is mediated by mutual antagonism with BRCA1
  • mitotic kinases phosphorylate RNF8 and TP53BP1 to inhibit their recruitment to DSB-flanking chromatin
  • USP28 is recruited to double-strand breaks in a manner that requires the tandem BRCT domains of the DDR protein TP53BP1
  • damage site-bound TP53BP1 whose binding signal is known to be generated by RNF8 and RNF168, and unbound bulk TP53BP1 whose ensuing degradation is regulated by RNF8 and RNF168
  • UBE2L3 regulates both the steady-state and replicative stress-induced ubiquitination and proteasome-dependent degradation of the tumor suppressor TP53-binding protein 1 (TP53BP1)
  • mitotic phosphorylation of TP53BP1 by PLK1 and CDK1 that impairs the ability of TP53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage
  • KDM1A, RNF168 and TP53BP1 interacted with each other directly
  • only NUP153 is needed for proper nuclear import of TP53BP1 and SENP1-dependent sumoylation of TP53BP1
  • TPX2/AURKA heterodimer, nominally considered a mitotic kinase complex, is a novel binding partner of TP53BP1
  • cell & other
    REGULATION
    Other UV light-induced phosphorylation
    BRCA1 loss activates CTSL1-mediated degradation of TP53BP1
    dephosphorylation by PPP4C enables the recruitment of TP53BP1 to double-strand DNA breaks
    acetylation limits TP53BP1 association with damaged chromatin to promote homologous recombination
    phosphorylation of TP53BP1 at the N terminus is involved in the replicative stress-induced TP53BP1 degradation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    Riddle disease associated with defects in TP53BP1-mediated DNA damage signaling
    constitutional        
    exclusion of TP53BP1 has a critical role in preventing telomeres from triggering cell cycle arrest
    Susceptibility to lupus erythematosus
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS