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: 7040.05   (req: < 5)

Gene RIFs: 1118   (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: 7040.05   (req: >= 5)

Gene RIFs: 1118   (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: 159

Tclin

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

Active Drug: 0