TP53BP1

Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.^[5][6][7]

TP53BP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GZH, 1KZY, 1XNI, 2G3R, 2IG0, 2LVM, 2MWO, 2MWP, 3LGF, 3LGL, 3LH0, 4CRI, 4RG2, 4X34, 5ECG
Identifiers
Aliases	TP53BP1, 53BP1, p202, p53BP1, TP53, TDRD30, tumor protein p53 binding protein 1
External IDs	OMIM: 605230; MGI: 1351320; HomoloGene: 4137; GeneCards: TP53BP1; OMA:TP53BP1 - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q15.3 Start 43,403,061 bp[1] End 43,510,728 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 E5 Start 121,023,762 bp[2] End 121,101,888 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pituitary gland anterior pituitary gonad ventricular zone stromal cell of endometrium Achilles tendon right uterine tube ganglionic eminence middle temporal gyrus sural nerve Top expressed in primary oocyte ascending aorta substantia nigra secondary oocyte ciliary body fossa renal corpuscle Rostral migratory stream aortic valve condyle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding transcription coregulator activity p53 binding protein binding ubiquitin modification-dependent histone binding damaged DNA binding methylated histone binding telomeric DNA binding sequence-specific DNA binding histone binding Cellular component cytoplasm nucleoplasm chromosome telomere chromosome, centromeric region kinetochore nuclear body nucleus replication fork site of double-strand break DNA repair complex Biological process regulation of transcription, DNA-templated cellular response to X-ray DNA damage checkpoint signaling positive regulation of DNA-binding transcription factor activity transcription, DNA-templated cellular response to DNA damage stimulus positive regulation of transcription, DNA-templated positive regulation of transcription by RNA polymerase II DNA repair protein homooligomerization double-strand break repair via nonhomologous end joining positive regulation of isotype switching negative regulation of double-strand break repair via homologous recombination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7158 27223 Ensembl ENSG00000067369 ENSMUSG00000043909 UniProt Q12888 P70399 RefSeq (mRNA) NM_001141979 NM_001141980 NM_005657 NM_001355001 NM_001290830 NM_013735 RefSeq (protein) NP_001135451 NP_001135452 NP_005648 NP_001341930 NP_001277759 NP_038763 Location (UCSC) Chr 15: 43.4 – 43.51 Mb Chr 2: 121.02 – 121.1 Mb PubMed search [3] [4]
Wikidata
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Clinical significance

53BP1 is underexpressed in most cases of triple-negative breast cancer.^[8]

DNA repair

DNA double-strand breaks (DSBs) are cytotoxic damages that can be repaired either by the homologous recombinational repair (HR) pathway or by the non-homologous end-joining (NHEJ) pathway. NHEJ, although faster than HR, is less accurate. The early divergent step between the two pathways is end resection, and this step is regulated by numerous factors. In particular, BRCA1 and 53BP1 play a role in determining the balance between the two pathways.^[9][10] 53BP1 restricts resection and promotes NHEJ.

Age-associated deficient repair

Ordinarily during the G1 phase of the cell cycle, when a sister chromatid is unavailable for HR, NHEJ is the predominant pathway for repairing DNA double-strand breaks (DSBs). However, as individuals age, recruitment of 53BP1 to DSBs during G1 becomes deficient.^[11] The absence of 53BP1 at such DSBs appears to promote the alternative error-prone repair process Alt-EJ.^[11] This repair process, also referred to as microhomology-mediated end joining, is highly inaccurate and likely contributes to the aging process.

Interactions

53BP1 has been shown to physically interact with:

• Histone H4 dimethylated or monomethylated at Lysine 20^[12]
• Histone H2A or Histone H2A.X ubiquitinated at Lysine 15^[13]
• p53^{[14][15][16][17]}
• DYNLL1^[18]

• TIRR (NUDT16L1)^[19][20]