ATM serine/threonine kinase | Other PIKK family kinases | IUPHAR Guide to IMMUNOPHARMACOLOGY

Top ▲

ATM serine/threonine kinase

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
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
A-T mutated homolog | ATC | ATD | ATDC | TEL1 | ataxia telangiectasia mutated
Database Links
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
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
KU-55933 Hs Inhibition 8.7 pKi 3
pKi 8.7 (Ki 2.2x10-9 M) [3]
berzosertib Hs Inhibition 7.5 pKi 1
pKi 7.5 (Ki 3.4x10-8 M) [1]
AZD0156 Hs Inhibition 9.2 pIC50 4
pIC50 9.2 (IC50 5.8x10-10 M) [4]
KU-60019 Hs Inhibition 8.2 pIC50 2
pIC50 8.2 (IC50 6.3x10-9 M) [2]
KU-55933 Hs Inhibition 7.9 pIC50 3
pIC50 7.9 (IC50 1.3x10-8 M) [3]
CP466722 Hs Inhibition - - 5
[5]
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
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
click arrow to show/hide IEA associations
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
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

Show »

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 20/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1934.