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FLASH GENE
Symbol TP53BP2 contributors: mct - updated : 27-03-2013
HGNC name tumor protein p53 binding protein, 2
HGNC id 12000
Location 1q41      Physical location : 223.967.595 - 224.033.674
Synonym name
  • BCL2-binding protein, apoptosis-stimulating protein of p53, 2
  • NY-REN-51 antigen
  • BCL2-binding protein
  • tumor suppressor p53-binding protein 2
  • Synonym symbol(s) PPP1R13A, ASPP2, 53BP2, BBP
    DNA
    TYPE functioning gene
    STRUCTURE 65.08 kb     18 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    DUSP10 1q32 dual specificity phosphatase 10 LOC391166 1 similar to capicua homolog LOC388740 1 LOC388740 LOC388741 1 LOC388741 FLJ13840 1q42.12 hypothetical protein FLJ13840 TAF1A 1q42 TATA box binding protein (TBP)-associated factor, RNA polymerase I, A, 48kDa LOC388742 1 similar to RIKEN cDNA A930039G15 gene FLJ12806 1q42.12 hypothetical protein FLJ12806 FLJ32421 1q42.12 hypothetical protein FLJ32421 LOC343087 1q42.12 similar to chromosome 14 open reading frame 24 DISP1 1q42.12 dispatched homolog 1 (Drosophila) FLJ10052 1q42.12 hypothetical protein FLJ10052 FLJ35728 1q42.12 hypothetical protein FLJ35728 LOC388743 1 similar to calpain 8 CAPN2 1q41-q42 calpain 2, (m/II) large subunit TP53BP2 1q42.1 tumor protein p53 binding protein, 2 LOC391167 1 similar to prohibitin LOC343354 1q42.12 similar to beta actin LOC388744 1 similar to bA476I15.3 (novel protein similar to septin) LOC388745 1 LOC388745 LOC347813 1q42.12 hypothetical protein LOC347813 KIAA0483 1q42.12 KIAA0483 protein LOC388746 1 LOC388746 DEGS 1q41 degenerative spermatocyte homolog, lipid desaturase (Drosophila) NVL 1q41-q42.2 nuclear VCP-like HSPC163 1q42.12 HSPC163 protein WDR26 1q42.12-q42.13 WD repeat domain 26 FLJ38993 1q42.13 hypothetical protein FLJ38993 MGC27277 1q42.13 hypothetical protein MGC27277 LOC388747 1 similar to RIKEN cDNA A230079K17 LOC127602 1q42.13 similar to KIAA1697 protein LBR 1q42.1 lamin B receptor ENAH 1q41 enabled homolog (Drosophila) SRP9 1q42.13 signal recognition particle 9kDa LEFTY3 1q42.1 LEFTY family pseudogene EPHX1 1q42.1 epoxide hydrolase 1, microsomal (xenobiotic) KIAA0792 1q42.13 epoxide hydrolase 1, microsomal (xenobiotic) LEFTB 1q42.1 left-right determination, factor B P5CR2 1q42.13 pyrroline 5-carboxylate reductase isoform EBAF 1q42.1 endometrial bleeding associated factor (left-right determination, factor A; transforming growth factor beta superfamily) FLJ35382 1q42.13 hypothetical protein FLJ35382 H3F3A 1q41 H3 histone, family 3A ACBD3 1q42.13 acyl-Coenzyme A binding domain containing 3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - - 4500 - 105 - 2013 2324830
    18 - 4670 - 1134 - 2013 2324830
  • 53BP2L
  • 19 - 4802 - 1005 - 2013 2324830
  • BBP (also known as 53BP2S)
  • an alternatively spliced ASPP2 isoform lacking the N terminus, and defective in binding Ras-GTP and stimulating Raf/MEK/ERK signaling
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrineparathyroid   highly
    Nervousbrain   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal beta-GRASP ubiquitin-like fold suggesting a possible role in binding to other proteins in the apoptotic response network and thus mediating their selective pro-apoptotic functiona proline-rich sequence,
  • a small G protein Ras-association domain
    the ASPP2 N terminus
  • a proline-rich domain
  • C terminus containing four ankyrin (Ank) repeats and a SH3 domain, which mediate its interactions with numerous partner proteins such as TP53, NFB, and BCL2, important for promoting TP53-dependent apoptosis
  • HOMOLOGY
    interspecies homolog to murine Tp53bp2
    homolog to C.elegans F11E6.7
    intraspecies homolog to PPP1R12a
    Homologene
    FAMILY apoptosis stimulating proteins of p53 (ASPP) family
    CATEGORY adaptor , regulatory , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    text
  • localizes to the cytoplasm and plasma membrane to mediate extranuclear functions
  • basic FUNCTION
  • enhancing p53-induced apoptosis, the DNA binding and transactivation function of TP53
  • impeding cell cycle progression at G2/M (cell cycle control)
  • playing a role in TP53-related signal transduction pathways
  • regulating the tumor suppression function of TP53
  • SH3/SH2 adaptor protein
  • haploinsufficient tumor suppressor that shares overlapping function with TP53 in tumor suppression
  • induces apoptosis by inhibiting functional sites of the antiapoptotic BCL2 proteins
  • specifically stimulates the apoptotic response mediated by the tumor suppressor TP53, by enhancing the transactivation function of TP53 on promoters of proapoptotic genes
  • having ability to regulate the apoptotic function of TP53 and its family members, TP63 and TP73
  • regulates epithelial cell polarity in cooperation with PARD3 to form an active PAR complex
  • mediates HRAS-induced senescence and inhibits autophagy
  • having tumor suppressor function via direct interaction with Ras-GTP to stimulate Ras-induced senescence in nontransformed human cells
  • is an important component of Ras-induced senescence, expanding on the complexity of TP53BP2 tumor suppressor function
  • implicated in control of cell adhesion and polarity through its effect on the PAR complex
  • implicated in control of cell adhesion and polarity through its effect on the PAR complex
  • ability of TP53BP2 to maintain cellular polarity is vital to CNS development, suggesting that the identified STAT1/TP53BP2 pathway may connect tumor suppression and cell polarity to neuroinflammation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component TP53BP2–Bcl complex may maintain the balance between the pro- and antiapoptotic activity of both proteins
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding directly to p53, p63 and p73 (to central region of wild type TP53)
  • BCL2, P65RelA, APCL
  • transcriptional targets of E2F1 (provides another mechanism by which E2F cooperates with TP53 to induce apoptosis)
  • facilitates the interaction between TAZ and PPP1CA to promote TAZ dephosphorylation
  • modulates oncogenic HRAS-induced autophagic activity to dictate the cellular response to HRAS: to proliferate or senescence
  • binds to RAS GTP, at the plasma membrane and stimulates RAS-induced signaling and pERK1/2 levels via promoting RAS GTP loading
  • interacts with activated GTP-bound Ras independent of TP53
  • SIAH2 controls TP53BP2 availability, with concomitant effect on epithelial cell polarity, and is involved in regulation of tight junction (TJ) integrity and cell polarity under hypoxia, through its regulation of TP53BP2 stability
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type TP53
    tumoral     --low  
    frequently downregulated in breast carcinoma expressing wild--type TP53
    Susceptibility to gastric cancer
    Variant & Polymorphism other variant increasing the risk of gastric cancer
    Candidate gene
  • important potential target for the development of anticancer drugs that will stimulate apoptosis by interfering with its regulation; the TP53BP2–BCL2 interaction at the molecular and cellular levels could serve as a basis for such novel anticancer drug leads
  • Marker
    Therapy target target for cancer therapy
    ANIMAL & CELL MODELS