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ATM serine/threonine kinase

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Target not currently curated in GtoImmuPdb

Target id: 1934

Nomenclature: ATM serine/threonine kinase

Abbreviated Name: ATM

Family: Other PIKK family kinases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 3056 11q22-q23 ATM ATM serine/threonine kinase
Mouse - 3066 9 C-D Atm ataxia telangiectasia mutated
Rat - 3064 8q24 Atm ATM serine/threonine kinase
Previous and Unofficial Names Click here for help
A-T mutated homolog | ATC | ATD | ATDC | TEL1 | ataxia telangiectasia mutated
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
KU-55933 Small molecule or natural product Primary target of this compound Hs Inhibition 8.7 pKi 3
pKi 8.7 (Ki 2.2x10-9 M) [3]
berzosertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pKi 1
pKi 7.5 (Ki 3.4x10-8 M) [1]
AZD0156 Small molecule or natural product Primary target of this compound Hs Inhibition 9.2 pIC50 4
pIC50 9.2 (IC50 5.8x10-10 M) [4]
KU-60019 Small molecule or natural product Primary target of this compound Hs Inhibition 8.2 pIC50 2
pIC50 8.2 (IC50 6.3x10-9 M) [2]
KU-55933 Small molecule or natural product Primary target of this compound Hs Inhibition 7.9 pIC50 3
pIC50 7.9 (IC50 1.3x10-8 M) [3]
CP466722 Small molecule or natural product Primary target of this compound Hs Inhibition - - 5
[5]
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:1903978 regulation of microglial cell activation IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0002331 pre-B cell allelic exclusion ISS
GO:0030889 negative regulation of B cell proliferation IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0030889 negative regulation of B cell proliferation IMP
click arrow to show/hide IEA associations
GO:1903978 regulation of microglial cell activation IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 3 GO processes
GO:0002331 pre-B cell allelic exclusion ISS
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GO:0033151 V(D)J recombination IEA
GO:0048538 thymus development IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0002331 pre-B cell allelic exclusion ISS
GO:0030889 negative regulation of B cell proliferation IMP
click arrow to show/hide IEA associations
GO:1903978 regulation of microglial cell activation IEA
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Ataxia-telangiectasia
Disease Ontology: DOID:12704
OMIM: 208900
Orphanet: ORPHA100
Disease:  Ataxia-telangiectasia variant
Orphanet: ORPHA370109
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Disease:  Chronic lymphocytic leukemia
Synonyms: B-cell chronic lymphocytic leukemia [Orphanet: ORPHA67038]
Chronic lymphatic leukemia
Chronic lymphoid leukemia
Disease Ontology: DOID:1040
OMIM: 151400
Orphanet: ORPHA67038
Disease:  Combined cervical dystonia
Orphanet: ORPHA370114
Disease:  Mantle cell lymphoma
Description: MCL is an aggressive form of non-Hodgkin’s lymphoma (NHL; median survival of 3-4 years) that arises from B-cells originating within the mantle zone of lymphatic follicles. In the US, around six percent of all new NHL cases are MCL.
Disease Ontology: DOID:0050746
Orphanet: ORPHA52416
General Comments
Ataxia telangiectasia mutated (ATM) kinase is critical in sensing and repairing DNA double-stranded breaks, being involved in the DNA damage response (DDR) pathway.

References

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1. Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W et al.. (2012) Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis, 3: e441. [PMID:23222511]

2. Golding SE, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA et al.. (2009) Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol. Cancer Ther., 8 (10): 2894-902. [PMID:19808981]

3. Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM, Orr AI, Reaper PM, Jackson SP, Curtin NJ, Smith GC. (2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res., 64 (24): 9152-9. [PMID:15604286]

4. Pike KG, Barlaam B, Cadogan E, Campbell A, Chen Y, Colclough N, Davies NL, de-Almeida C, Degorce SL, Didelot M et al.. (2018) The Identification of Potent, Selective, and Orally Available Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase: The Discovery of AZD0156 (8-{6-[3-(Dimethylamino)propoxy]pyridin-3-yl}-3-methyl-1-(tetrahydro-2 H-pyran-4-yl)-1,3-dihydro-2 H-imidazo[4,5- c]quinolin-2-one). J. Med. Chem., 61 (9): 3823-3841. [PMID:29683659]

5. Rainey MD, Charlton ME, Stanton RV, Kastan MB. (2008) Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res, 68 (18): 7466-74. [PMID:18794134]

How to cite this page

Other PIKK family kinases: ATM serine/threonine kinase. Last modified on 08/05/2018. Accessed on 27/10/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1934.