ATR — ATR serine/threonine kinase
ATR belongs to a gene co-expression module in 2 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
ATR's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Gamma-delta T cells | ER Antigen Processing Protein processing & ER | ACLY, ATL3, CANX, DCTN1, DDB1, ERAP1, FOXJ3, ITCH +9 more | |
| Macrophages | DNA Damage Response Stress | APAF1, ARHGAP35, ATP11C, CDC42SE2, CENATAC, CEP192, CEP85L, EPB41 +19 more | View in SCUBA |
About the gene
| Synonyms | FRP1, MEC1, SCKL, SCKL1 |
|---|---|
| Chromosome | 3: 142449007-142578733 |
| Predicted location | Membrane |
| Essential gene | Yes |
| Protein class | Cancer-related genes, Disease related genes, Enzymes, Essential proteins, Human disease related genes, Potential drug targets, Predicted membrane proteins |
| Molecular function | DNA-binding, Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | DNA damage, DNA repair |
Function
Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication. Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2. Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress. Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1. Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly. Involved in the inflammatory response to genome instability and double- stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture. The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity. Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity).
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.