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TP53BP1

This gene encodes a protein that functions in the DNA double-strand break repair pathway choice, promoting non-homologous end joining (NHEJ) pathways, and limiting homologous recombination. This protein plays multiple roles in the DNA damage response, including promoting checkpoint signaling following DNA damage, acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin, and promoting NHEJ pathways by limiting end resection following a double-strand break. These roles are also important during V(D)J recombination, class switch recombination and at unprotected telomeres. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]
Full Name
tumor protein p53 binding protein 1
Function
Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:22553214, PubMed:23333306, PubMed:17190600, PubMed:21144835, PubMed:27153538, PubMed:28241136).
Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23727112, PubMed:23333306, PubMed:27153538).
In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136).
Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:23760478, PubMed:27153538, PubMed:28241136, PubMed:17190600).
Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425).
Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity).
In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity).
Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112).
Biological Process
Biological Process cellular response to DNA damage stimulus Source:UniProtKB2 Publications
Biological Process cellular response to X-ray Source:Ensembl
Biological Process DNA damage checkpoint signaling Source:GO_Central1 Publication
Biological Process double-strand break repair via nonhomologous end joining Source:UniProtKB4 Publications
Biological Process negative regulation of double-strand break repair via homologous recombination Source:UniProtKB2 Publications
Biological Process positive regulation of DNA-binding transcription factor activity Source:BHF-UCL1 Publication
Biological Process positive regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process positive regulation of isotype switching Source:UniProtKB1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:BHF-UCL1 Publication
Biological Process protein homooligomerization Source:UniProtKB1 Publication
Cellular Location
Nucleus
Chromosome
Chromosome, centromere, kinetochore
Localizes to the nucleus in absence of DNA damage (PubMed:28241136).
Following DNA damage, recruited to sites of DNA damage, such as double stand breaks (DSBs): recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:23333306, PubMed:23760478, PubMed:24703952, PubMed:28241136, PubMed:17190600).
Associated with kinetochores during mitosis (By similarity).
Involvement in disease
A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.
PTM
Asymmetrically dimethylated on Arg residues by PRMT1. Methylation is required for DNA binding.
Phosphorylated at basal level in the absence of DNA damage (PubMed:11042216, PubMed:11331310).
Phosphorylated by ATM in response to DNA damage: phosphorylation at different sites promotes interaction with different set of proteins: phosphorylation at the N-terminus by ATM (residues from 6-178) promotes interaction with PAXIP1 and non-homologous end joining (NHEJ) of dysfunctional telomeres (PubMed:23727112).
Phosphorylation by ATM at residues that are located more C-terminus (residues 300-650) leads to promote interaction with RIF1 (PubMed:23727112, PubMed:23333306, PubMed:28241136).
Interaction with RIF1 leads to disrupt interaction with NUDT16L1/TIRR (PubMed:28241136).
Phosphorylation at Thr-1609 and Ser-1618 in the UDR motif blocks interaction with H2AK15ub (PubMed:24703952).
Dephosphorylated by PPP4C (PubMed:24703952).
Hyperphosphorylation during mitosis correlates with its exclusion from chromatin and DNA lesions. Hyperphosphorylated in an ATR-dependent manner in response to DNA damage induced by UV irradiation (PubMed:17553757, PubMed:21144835).
Dephosphorylated by PPP5C (PubMed:19176521).

Anti-TP53BP1 antibodies

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Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: 1B9
Application*: SE, E
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBYJT-4259
Application*: WB, IH
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human
Clone: CBYJT-4260
Application*: WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: CBYJT-4261
Application*: E, F, IH, WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: CBYJT-4262
Application*: E, F, IH, WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: CBYJT-4263
Application*: E
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBYJT-4264
Application*: WB, IH
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBYJT-4265
Application*: E, F, P, WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBYJT-4266
Application*: WB, IH
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: CBYJT-4267
Application*: SE, E
Target: TP53BP1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: 1285A
Application*: WB, IC
Target: TP53BP1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse
Clone: 1285C
Application*: WB, IH, IF, P, F
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human
Clone: 19/53BP1
Application*: WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 6B3E10
Application*: E, F
Target: TP53BP1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Rat, Mouse, Monkey
Clone: D4H11
Application*: WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgM
Specificity: Human, Mouse
Clone: 5H36
Application*: IP, WB
Target: TP53BP1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 5H37
Application*: IC, IP, WB
Target: TP53BP1
Host: Mouse
Specificity: Human, Mouse, Rabbit
Clone: 54.2
Application*: IP, WB
Target: TP53BP1
Host: Mouse
Specificity: Human, Mouse, Rabbit
Clone: LX011
Application*: IP, WB
Target: TP53BP1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse
Clone: CB-250-1H11
Application*: WB, IP, IHC
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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