InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ATR

Summary

InnateDB Protein

IDBP-59525.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ATR

Protein Name

ataxia telangiectasia and Rad3 related

Synonyms

FCTCS; FRP1; MEC1; SCKL; SCKL1;

Species

Homo sapiens

Ensembl Protein

ENSP00000343741

InnateDB Gene

IDBG-59521 (ATR)

Protein Structure

UniProt Annotation

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, 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/H2AFX 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. {ECO:0000269PubMed:10597277, ECO:0000269PubMed:10608806, ECO:0000269PubMed:10859164, ECO:0000269PubMed:11114888, ECO:0000269PubMed:11418864, ECO:0000269PubMed:11673449, ECO:0000269PubMed:11721054, ECO:0000269PubMed:11865061, ECO:0000269PubMed:12526805, ECO:0000269PubMed:12791985, ECO:0000269PubMed:12814551, ECO:0000269PubMed:14657349, ECO:0000269PubMed:14729973, ECO:0000269PubMed:14742437, ECO:0000269PubMed:15210935, ECO:0000269PubMed:15314022, ECO:0000269PubMed:15496423, ECO:0000269PubMed:16260606, ECO:0000269PubMed:21144835, ECO:0000269PubMed:9427750, ECO:0000269PubMed:9636169, ECO:0000269PubMed:9925639}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:11114888, ECO:0000269PubMed:11721054, ECO:0000269PubMed:11865061, ECO:0000269PubMed:12814551, ECO:0000269PubMed:14871897, ECO:0000269PubMed:16260606, ECO:0000269PubMed:18283122, ECO:0000269PubMed:8843195}. Nucleus, PML body {ECO:0000250}. Chromosome {ECO:0000250}. Note=Depending on the cell type, it can also be found in PML nuclear bodies. Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling.

Disease Associations

Seckel syndrome 1 (SCKL1) [MIM:210600]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269PubMed:12640452}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cutaneous telangiectasia and cancer syndrome, familial (FCTCS) [MIM:614564]: A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well. {ECO:0000269PubMed:22341969}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary. {ECO:0000269PubMed:11470508, ECO:0000269PubMed:8610130, ECO:0000269PubMed:8843195}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 125 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	125 [view]
Protein-Protein	121 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	4 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0032405	MutLalpha complex binding
GO:0032407	MutSalpha complex binding

Biological Process

GO:0000077	DNA damage checkpoint
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006468	protein phosphorylation
GO:0006974	cellular response to DNA damage stimulus
GO:0007049	cell cycle
GO:0007275	multicellular organismal development
GO:0008156	negative regulation of DNA replication
GO:0018105	peptidyl-serine phosphorylation
GO:0034644	cellular response to UV
GO:0042493	response to drug
GO:0043393	regulation of protein binding
GO:0043517	positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0046777	protein autophosphorylation
GO:0071480	cellular response to gamma radiation
GO:0090399	replicative senescence

Cellular Component

GO:0001741	XY body
GO:0005654	nucleoplasm
GO:0005694	chromosome
GO:0016605	PML body

Protein Structure and Domains

PDB ID

InterPro

IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003151 PIK-related kinase, FAT
IPR003152 PIK-related kinase, FATC
IPR011009 Protein kinase-like domain
IPR012993 UME
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold
IPR021133 HEAT, type 2

PFAM

PF00454
PF02259
PF02260
PF08064

PRINTS

PIRSF

SMART

SM00146
SM00802

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q13535