Anti-ATM, phosphoSer1981, clone 10H11.E12

Anti-ATM, phosphoSer1981, clone 10H11.E12

Chemicon (Millipore)

Reacts with ATM Kinase phosphorylated at serine 1981. Clone 10H11.E12 is covered by US patent No. 6,916,627 and 7,108,992.

phosphoSer1981

Synthetic peptide corresponding to amino acids 1974-1988 of human ATM (SLAFEEG[pS]QSTTISS).

Phosphorylation

10H11.E12

IgG1κ

ATM is a 370 kDa nuclear phosphoprotein involved in the autosomal recessive disease Ataxia Telangiectasia (AT). Ataxia telangiectasia (AT) is a debilitating neurodegenerative disease that occurs early in childhood, resulting in ataxic movements and speech defects caused by cerebellar degeneration. The underlying cause of the disease is a biochemical dysfunction in the cellular response to specific types of DNA damage, correlated with mutations in the protein kinase ATM (Ataxia telangiectasia mutated). ATM not only is key in the signaling cascade that responds to DNA double-stranded breaks, but it also controls cell-cycle checkpoints and is therefore important in cancer prevention.

• Human
• Mouse

Western blot: Detects a 370 kDa protein in crude extracts from irradiated human foreskin or mouse 3T3L1 cells.

Immunocytochemistry: Foci are detected in irradiated human and mouse fibroblasts.

Immunoprecipitation: The antibody immunoprecipitates ATM from irradiated human and mouse cells.

Optimal working dilutions must be determined by end user.

Irradiated normal Human fibroblasts (no reactivity against non-irradiated cell extracts)

Purified immunoglobulin presented as a liquid in 0.02M phosphate buffer containing 0.25M NaCl and 0.1% sodium azide.

Maintain at 2-8°C in undiluted aliquots for up to 6 months from date of receipt.



This antibody and certain aspects of its use are disclosed and claimed in pending U.S. Patent Applications published as U.S. Patent Publication Nos. 2003/0077661 and 2003/0157572.

Q13315

• NM_000051.3
• NM_138292.3

• ATM
• ATD
• AT
• TELO1
• ATA
• AT1
• ATC
• T-PLL
• DKFZp781A0353
• ATE
• TEL1
• ATDC
• TPLL
• MGC74674
• EC 2.7.11.1

Ataxia Telangiectasia Mutated

Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.

• Immunoprecipitation
• Western Blotting
• Immunocytochemistry

The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. Two transcript variants encoding different isoforms have been found for this gene.

FUNCTION: SwissProt: Q13315 # 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 involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates 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.
SIZE: 3056 amino acids; 350644 Da
SUBUNIT: Exists in monomeric and tetrameric state. Binds DNA ends, p53/TP53, ABL1, BRCA1, NBN/nibrin and TERF1. Part of the BRCA1- associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. DNA damage promotes association with RAD17. Interacts with EEF1E1. This interaction, which takes place independently of TP53, is induced by DNA damage that may occur during genotoxic stress or cell growth. Interacts with DCLRE1C. Interacts with MYST1. Interacts with HTATIP.
SUBCELLULAR LOCATION: Nucleus. Cytoplasmic vesicle. Note=Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin.
TISSUE SPECIFICITY: Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes.DOMAIN:SwissProt: Q13315 The FATC domain is required for interaction with HTATIP.
PTM: Phosphorylated by ARK5. Autophosphorylated on Ser-1981 upon DNA damage. & Acetylated by HTATIP upon DNA damage; which is required for autophosphorylation and subsequent activation.
DISEASE: SwissProt: Q13315 # Defects in ATM are the cause of ataxia telangiectasia (AT) [MIM:208900]; also known as Louis-Bar syndrome, which includes four complementation groups: A, C, D and E. This rare recessive disorder is characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. AT patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation. & Defects in ATM contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients. & Defects in ATM contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL). & Defects in ATM contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.
SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily. & Contains 1 FAT domain. & Contains 1 FATC domain. & Contains 1 PI3K/PI4K domain.

Chemicon

ATM (Ataxia Telangiectasia Mutated kinase) and ATR (Ataxia Telangiectasia and Rad3-related kinase) are related kinases that regulate cell cycle checkpoints and DNA repair. ATM is activated in response to DNA damage and serves to arrest further cell division before the damage can be repaired. Mutation in the ATM gene results in the autosomal recessive disease ataxia telangiectasia (AT). The identified substrates for ATM are p53, p95/NBS1, MDM2, Chk2, BRCA1, CtIP, 4E-BP1 and Chk1. ATM activates p53, increasing p21/Cip1/Waf1 levels, thus blocking activation of Cdk2. That results in Rb hypophosphorylation and blockage of the G1/S transition. Separately, ATM also phosphorylates and activates Chk1, which phosphorylates Cdc25C. This inactivates Cdc25C and prevents it from dephosphorylating the inhibitory phosphotyrosine residue on cdc2/Cdk1, thus preventing the G2/M transition. The essential requirement for the substrates of ATM/ATR is S/TQ. Hydrophobic amino acids at positions -3 and -1, and negatively charged amino acids at position +1 are positive determinants for substrate recognition by these kinases. Positively charged residues surrounding the S/TQ are negative determinants for substrate phosphorylation. The complex phenotype of cells derived from patients with AT suggests that ATM has additional cellular substrates. In unirradiated cells, ATM is present as an inactive homodimer or multimer. Double-stranded breaks in DNA caused by ionizing radiation cause rapid ATM kinase activation through dissociation of this complex and ATM autophosphorylation at Ser1981.

Anti-ATM, phosphoSer1981, clone 10H11.E12

1 mg/mL

Monoclonal Antibody

100 µg

Purified

Mouse