Tchem ATM 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

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

DTO Classes

Protein / Kinase / Protein Kinase / Atypical Group / Pikk Family / Serine-protein Kinase Atm

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: 5651.91   (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: 5651.91   (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: 100

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (100)

Explore Active Ligands

1 – 10 of 100

berzosertib

ATMTchem Kinase

pKi : 7.82

torin 2

ATMTchem Kinase

pIC50 : 9.6

dactolisib

ATMTchem Kinase

pIC50 : 8.85

CHEMBL4565988

ATMTchem Kinase

pIC50 : 8.7

6-Cyano-4-[(2-ethylbutyl)amino]-3-quinolinecarboxamide

ATMTchem Kinase

pIC50 : 8.1

CHEMBL4518369

ATMTchem Kinase

pIC50 : 7.7

AZD0156

ATMTchem Kinase

pIC50 : 10.4

KU-55933

ATMTchem Kinase

pKi : 8.66

KU-60019

ATMTchem Kinase

pIC50 : 8.22

US9428503, 26

ATMTchem Kinase

pIC50 : 9.82

Protein-Protein Interactions (773)

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1 – 10 of 773

• See Interactions on String-DB

BSG

Tbio

Novelty:  0.0010285

p_int:  0.999703694

p_ni:  0.000296306

Score:  0.176

Data Source:  BioPlex,STRINGDB

NPY2R

Tchem

Family:  GPCR

Novelty:  0.01177255

p_int:  0.999453496

p_ni:  0.000546504

Data Source:  BioPlex

LPAR4

Tchem

Family:  GPCR

Novelty:  0.02200758

p_int:  0.998722317

p_ni:  0.001277683

Data Source:  BioPlex

OPALIN

Tdark

Novelty:  0.08221612

p_int:  0.996389559

p_ni:  0.003610441

Data Source:  BioPlex

CYB5B

Tbio

Novelty:  0.09395308

p_int:  0.995539998

p_ni:  0.004460002

Data Source:  BioPlex

OPRM1

Tclin

Family:  GPCR

Novelty:  0.0003701

p_int:  0.991659554

p_ni:  0.008340433

p_wrong:  1.3e-8

Data Source:  BioPlex

CD70

Tbio

Novelty:  0.00420393

p_int:  0.985072571

p_ni:  0.014927429

Data Source:  BioPlex

EDNRB

Tclin

Family:  GPCR

Novelty:  0.00053875

p_int:  0.960986668

p_ni:  0.039013332

Score:  0.194

Data Source:  BioPlex,STRINGDB

CD274

Tclin

Novelty:  0.00013449

p_int:  0.933939845

p_ni:  0.066060154

p_wrong:  1e-9

Score:  0.345

Data Source:  BioPlex,STRINGDB

P2RY8

Tbio

Family:  GPCR

Novelty:  0.05574297

p_int:  0.897345414

p_ni:  0.102654586

Data Source:  BioPlex

Nearest Tclin Targets (4)

Explore Nearest Tclin Targets

Upstream (3)

Downstream (1)

1 – 3 of 3

MAP2K2

Tclin

Family:  Kinase

KEGG Distance:  3

Common Pathways:  7

1: Human T-cell leukemia virus 1 infection

2: FoxO signaling pathway

3: MicroRNAs in cancer

4: Human papillomavirus infection

more:  3 more common pathways

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  3

Common Pathways:  7

1: Human T-cell leukemia virus 1 infection

2: FoxO signaling pathway

3: MicroRNAs in cancer

4: Human papillomavirus infection

more:  3 more common pathways

IL6

Tclin

Family:  Other

KEGG Distance:  3

Common Pathways:  4

1: Human T-cell leukemia virus 1 infection

2: FoxO signaling pathway

3: Transcriptional misregulation in cancer

4: Cellular senescence

Pathways (94)

Reactome (47)

KEGG (13)

PathwayCommons (12)

WikiPathways (22)

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

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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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (65)

Functions (8)

Components (5)

Processes (52)

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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

Disease Associations ()

No disease associations found

GWAS Traits (32)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	3	3	3		93.4
mean corpuscular hemoglobin concentration	EFO_0004528	2	2	2		92.5
mean corpuscular volume	EFO_0004526	3	3	3		91.7
mosaic loss of chromosome Y measurement	EFO_0007783	3	2	3		90.3
platelet count	EFO_0004309	3	3	3		86.9

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	3		93.4
mean corpuscular hemoglobin concentration	EFO_0004528	2		92.5
mean corpuscular volume	EFO_0004526	3		91.7
mosaic loss of chromosome Y measurement	EFO_0007783	3		90.3
platelet count	EFO_0004309	3		86.9

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
ATP-binding
Cell cycle
Complete proteome
Cytoplasmic vesicle
Disease mutation
DNA damage
DNA-binding
Kinase

GWAS Trait Find Similar Targets

No Header	No Header
cutaneous melanoma
eosinophil count
eosinophil percentage of leukocytes
erythrocyte count
granulocyte count
leukocyte count
lymphocyte count
lymphocyte percentage of leukocytes
mean corpuscular hemoglobin
mean corpuscular hemoglobin concentration

MGI Phenotype Find Similar Targets

No Header	No Header
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

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	ATM serine/threonine kinase	VGNC:11264	451530
Macaque	ATM serine/threonine kinase		100427400
Mouse	ataxia telangiectasia mutated	MGI:107202	11920
Rat	ATM serine/threonine kinase	RGD:1593265	300711
Dog	ATM serine/threonine kinase	VGNC:38233	479450

Species	Name	OMA	EggNOG	Inparanoid
Chimp	ATM serine/threonine kinase
Macaque	ATM serine/threonine kinase
Mouse	ataxia telangiectasia mutated
Rat	ATM serine/threonine kinase
Dog	ATM serine/threonine kinase

Publication Statistics

PubMed Score 5651.91

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PubTator Score 2255.25

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Text Mined References (1093)

GeneRif Annotations (876)

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PMID	Year	Title