Serine/threonine-protein kinase ATR (ATR)
The protein contains 2644 amino acids for an estimated molecular weight of 301367 Da.
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, 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. Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cellular response to DNA damage stimulus
Cellular response to gamma radiation
Cellular response to UV
DNA damage checkpoint signaling
DNA repair
DNA replication
Establishment of protein-containing complex localization to telomere
Establishment of RNA localization to telomere
Interstrand cross-link repair
Multicellular organism development
Negative regulation of DNA replication
Peptidyl-serine phosphorylation
Positive regulation of DNA damage response, signal transduction by p53 class mediator
Positive regulation of telomerase catalytic core complex assembly
Positive regulation of telomere maintenance via telomerase
Protein autophosphorylation
Protein localization to chromosome, telomeric region
Regulation of cellular response to heat
Regulation of signal transduction by p53 class mediator
Replication fork processing
Replicative senescence
Response to drug
Telomere maintenance
The reference OMIM entry for this protein is 210600
Seckel syndrome 1; sckl1
Sckl
Seckel-type dwarfism
Nanocephalic dwarfism
Microcephalic primordial dwarfism i
Bird-headed dwarfism
A number sign (#) is used with this entry because Seckel syndrome-1 (SCKL1) is caused by homozygous or compound heterozygous mutation in the ATR gene (601215) on chromosome 3q23.
DESCRIPTION
Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (Shanske et al., 1997). - Genetic Heterogeneity of Seckel Syndrome Other forms of Seckel syndrome include SCKL2 (606744), caused by mutation in the RBBP8 gene (604124) on chromosome 18q11; SCKL4 (613676), caused by mutation in the CENPJ gene (609279) on chromosome 13q12; SCKL5 (613823), caused by mutation in the CEP152 gene (613529) on chromosome 15q21; SCKL6 (614728), caused by mutation in the CEP63 gene (614724) on chromosome 3q22; SCKL7 (614851), caused by mutation in the NIN gene (608684) on chromosome 14q22; and SCKL8 (615807), caused by mutation in the DNA2 gene (601810) on chromosome 10q21. The report of a Seckel syndrome locus on chromosome 14q, designated SCKL3, by Kilinc et al. (2003) was found to be in error; seeHISTORY
.CLINICAL FEATURES
This condition was given the 2 names bird-headed dwarfism and nanocephaly by Virchow. Seckel (1960) produced the definitive publication based on 2 personally observed cases and 13 reliable plus 11 less reliable cases from the literature. In addition to dwarfism of 'low birth weight' type, the features are small head, large eyes, beak-like protrusion of the nose, narrow face, and receding lower jaw. Mental retardation is not as marked as might be expected in view of the very small brain. Multiple occurrence in the same sibship, increased frequency of parental consanguinity, occurrence in both sexes, and normal parents suggest autosomal recessive inheritance. Affected sisters were reported by Black (1961). Harper et al. (1967) reported brother and sister who strikingly resembled Seckel's cases 1 and 2, 2 other reported cases, and the 3 sibs reported by McKusick et al. (1967). Majewski and Goecke (1982) picked out 17 cases that agreed with Seckel's case 1 and 43 others (including the cases of McKusick et al., 1967) that they felt were not identical to that case. Butler et al. (1987) raised the question of whether there may be a subgroup of Seckel syndrome patients who have chromosome instability and/or hematologic problems. Chromosome breakage was demonstrated in 2 patients, one of whom had pancytopenia. Sugio et al. (1993) suggested that only 19 patients with classic Seckel syndrome had been reported--17 reviewed by Majewski and Goecke (1982) and 2 reported by Butler et al. (1987). They reported a Japanese case in which severe brain dysplasia was present. Hayani et al. (1994) described a female who was diagnosed with Seckel syndrome at 2 years of age. She was dwarfed (at 26 years of age she weighed 14.8 kg and was 113 cm tall), had severe microcephaly, and was mentally retarded. At age 26 years, she was diagnosed with acute myeloid leukemia (AML) by the study of blood marrow and peripheral blood. Chemotherapy produced severe toxicity with profound bone marrow aplasia. She died 2 months later. Although some patients with Seckel syndrome manifest anemia and other hematologic abnormalities, AML had not previously been reported. Hayani et al. (1994) suggested that patients with Seckel syndrome may be at risk of developing myelodysplasia and AML. Shanske et al. (1997) reporte ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 210600 was added.
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).