Tchem ATM Serine-protein kinase ATM

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine-protein Kinase Atm

Protein / Transferase / Kinase / Nucleotide Kinase / Serine-protein Kinase Atm

Protein / Nucleic Acid Binding / Serine-protein Kinase Atm

Protein Summary

Description

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. 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. [provided by RefSeq, Aug 2010]

Uniprot Accession IDs

• Q13315
• B2RNX5
• O15429
• Q12758
• Q16551
• Q93007
• Q9NP02
• Q9UCX7

Gene Name

• ATM

Ensembl ID

• ENST00000278616
• ENSP00000278616
• ENSG00000149311
• ENST00000452508
• ENSP00000388058

Symbol

• AT1
• ATA
• ATC
• ATD
• ATE
• ATDC
• TEL1
• TELO1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
hub protein	1
molecular function	0.99
protein domain	0.99

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4007.4   (req: < 5)

Gene RIFs: 876   (req: <= 3)

Antibodies: 1297   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4007.4   (req: >= 5)

Gene RIFs: 876   (req: > 3)

Antibodies: 1297   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 60

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 62

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (62)

Explore Active Ligands

1 – 10 of 62

CHEMBL1879463

ATMTchem Kinase

IC50: 8.15

CHEMBL222102

ATMTchem Kinase

Ki: 8.65999985

berzosertib

ATMTchem Kinase

Ki: 7.46999979

CHEMBL2140173

ATMTchem Kinase

IC50: 8.22

CHEMBL3923162

ATMTchem Kinase

IC50: 8.84

CHEMBL3932205

ATMTchem Kinase

IC50: 8.96

CHEMBL3955067

ATMTchem Kinase

IC50: 8.87

CHEMBL3912673

ATMTchem Kinase

IC50: 9

CHEMBL3890490

ATMTchem Kinase

IC50: 9.48

CHEMBL3983674

ATMTchem Kinase

IC50: 9.12

Protein Data Bank (2)

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (94)

Reactome (47)

KEGG (13)

PathwayCommons (12)

WikiPathways (22)

Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425)

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5

1 – 5 of 47

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Autodegradation of the E3 ubiquitin ligase COP1	52 targets	R-HSA-349425
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle Checkpoints	272 targets	R-HSA-69620
Reactome	Cellular Senescence	164 targets	R-HSA-2559583
Reactome	Cellular response to heat stress	100 targets	R-HSA-3371556

Name	Explore in Pharos	Explore in Source
Autodegradation of the E3 ubiquitin ligase COP1	52 targets	R-HSA-349425
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle Checkpoints	272 targets	R-HSA-69620
Cellular Senescence	164 targets	R-HSA-2559583
Cellular response to heat stress	100 targets	R-HSA-3371556

Gene Ontology Terms (65)

Functions (8)

Components (5)

Processes (52)

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Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
DNA-dependent protein kinase activity	Inferred from Direct Assay (IDA)	BHF-UCL
protein dimerization activity	Inferred from Direct Assay (IDA)	BHF-UCL
protein N-terminus binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein-containing complex binding	Inferred from Direct Assay (IDA)	BHF-UCL
1-phosphatidylinositol-3-kinase activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
DNA binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (773)

Explore Interacting Targets

1 – 10 of 773

• See Interactions on String-DB

BSG

Tbio

Novelty: 0.00077805

p_int: 0.999703694

p_ni: 0.000296306

Score: 0.176

Data Source: BioPlex,STRINGDB

NPY2R

Tchem

Family: GPCR

Novelty: 0.01163073

p_int: 0.999453496

p_ni: 0.000546504

Data Source: BioPlex

LPAR4

Tchem

Family: GPCR

Novelty: 0.03711071

p_int: 0.998722317

p_ni: 0.001277683

Data Source: BioPlex

OPALIN

Tdark

Novelty: 0.06813417

p_int: 0.996389559

p_ni: 0.003610441

Data Source: BioPlex

CYB5B

Tbio

Novelty: 0.11412954

p_int: 0.995539998

p_ni: 0.004460002

Data Source: BioPlex

OPRM1

Tclin

Family: GPCR

Novelty: 0.00035782

p_int: 0.991659554

p_ni: 0.008340433

p_wrong: 1.3e-8

Data Source: BioPlex

CD70

Tbio

Novelty: 0.00552433

p_int: 0.985072571

p_ni: 0.014927429

Data Source: BioPlex

EDNRB

Tclin

Family: GPCR

Novelty: 0.00055047

p_int: 0.960986668

p_ni: 0.039013332

Score: 0.194

Data Source: BioPlex,STRINGDB

CD274

Tclin

Novelty: 0.00020953

p_int: 0.933939845

p_ni: 0.066060154

p_wrong: 1e-9

Score: 0.345

Data Source: BioPlex,STRINGDB

P2RY8

Tbio

Family: GPCR

Novelty: 0.08044634

p_int: 0.897345414

p_ni: 0.102654586

Data Source: BioPlex

Publication Statistics

PubMed Score  4007.40

PubMed score by year

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PubTator Score  2255.25

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

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UniProt Keyword Find Similar Targets

3D-structure
Acetylation
ATP-binding
Cell cycle
Complete proteome
Cytoplasmic vesicle
Disease mutation
DNA damage
DNA-binding
Kinase

GWAS Trait Find Similar Targets

eosinophil count
eosinophil percentage of leukocytes
erythrocyte count
granulocyte count
mean corpuscular hemoglobin
mean corpuscular volume
melanoma
mosaic loss of chromosome Y measurement
myeloid white cell count
neutrophil count

MGI Phenotype Find Similar Targets

adipose tissue phenotype
behavior/neurological phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype