- Catalog number
- P00014
- Size / count
- 100 µg
- Dry ice
- Yes
- Hazardous
- No
- Discontinued
- No
- Background
- ATM, the gene mutated in the hereditary disease ataxia-telangiectasia, codes for a protein kinase that acts as a master regulator of cellular responses to DNA double-strand breaks. ATM is normally inactive and the question of how it is activated in the event of DNA damage (due to ionizing radiation for instance) is central to understanding its function. ATM protein is now shown to be present in undamaged cells as an inactive dimer. Low doses of ionizing radiation, which induce only a few DNA breaks, activate at least half of the total ATM protein present, possibly in response to changes in chromatin structure. The ATM gene encodes a 370-kDa protein that belongs to the phosphoinositide 3-kinase (PI (3) K) superfamily, but which phosphorylates proteins rather than lipids. The 350-amino-acid kinase domain at the carboxy terminus of this large protein is the only segment of ATM with an assigned function. Exposure of cells to IR triggers ATM kinase activity and this function is required for arrests in G1, S and G2 phases of the cell cycle. Several substrates of the ATM kinase participate in these IR-induced cell-cycle arrests. These include p53, Mdm2 and Chk2 in the G1 checkpoint; Nbs1, Brca1, FancD2 and SMC1 in the transient IR-induced S-phase arrest; and Brca1 and hRad17 in the G2/M checkpoint. This antibody is similar to the rabbit host antibody discussed by Bakkenist, C. J. & Kastan, M. B. in Nature 421, 499-506 (2003) .
- Synonyms
- ATM pS1981, AT mutated, AT protein, AT1, ATA, Ataxia telangiectasia gene mutated in human beings, Ataxia telangiectasia mutated, ATC
- Gene Name
- ATM
- UniProt
- Q13315
- Host
- Sheep
- Reactivity
- Human
- Immunogen
- This antibody was affinity purified from whole sheep serum prepared by repeated immunizations with a synthetic peptide corresponding to a region near serine 1981 of human ATM conjugated to KLH using maleimide.
- Clonality
- Polyclonal
- Tissue Specificity
- Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes.
- Applications
- ELISA, WB
- Field of Research
- Cancer, DNA/RNA, DNA Damage & Repair, DNA Damage Response, Epigenetics and Nuclear Signaling, Oncoproteins/Suppressors, Tumor Suppressors
- Purification
- This affinity-purified antibody is directed against human ATM and is useful in determining its presence in various assays. This polyclonal anti-ATM antibody recognizes the phosphorylated epitope in native and over-expressed proteins found in various tissues and extracts. Reactivity is observed against human ATM and cross-reactivity with ATM from other mammalian sources has not been tested.
- Concentration
- 1.0 mg/mL by UV absorbance at 280 nm
- Form
- Liquid (sterile filtered)
- Function
- Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response.
- Shipping Conditions
- Dry Ice Shipping
- Storage Conditions
- Store vial at -20°C prior to opening. Aliquot contents and freeze at -20°C or below for extended storage. Avoid cycles of freezing and thawing. Centrifuge product if not completely clear after standing at room temperature. This product is stable for several weeks at 4°C as an undiluted liquid. Dilute only prior to immediate use. Expiration date is one (1) year from date of opening.
- Observed Molecular Weight
- 350687 MW
- Gene Name Synonym
- Serine-protein kinase ATM
- Subcellular Location
- Nucleus. Cytoplasmic vesicle. Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin.
- Isotype
- IgG
- Contents
- 0.02 M Potassium Phosphate, 0.15 M Sodium Chloride, pH 7.2, 0.01% (w/v) Sodium Azide