DegronMD - Q13315(ATM)

FUNCTION: 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 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, FBXW7, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:9843217, PubMed:9733515, PubMed:10550055, PubMed:10766245, PubMed:10839545, PubMed:10910365, PubMed:10802669, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:30612738, PubMed:30886146, PubMed:26774286). 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. Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). {ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, ECO:0000269|PubMed:9843217}. View more >>

GO - Biological processes (BP): brain development [GO:0007420]; cellular response to DNA damage stimulus [GO:0006974]; cellular response to gamma radiation [GO:0071480]; cellular response to nitrosative stress [GO:0071500]; cellular response to retinoic acid [GO:0071300]; cellular response to X-ray [GO:0071481]; cellular senescence [GO:0090398]; determination of adult lifespan [GO:0008340]; DNA damage checkpoint signaling [GO:0000077]; DNA damage induced protein phosphorylation [GO:0006975]; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977]; double-strand break repair [GO:0006302]; double-strand break repair via homologous recombination [GO:0000724]; double-strand break repair via nonhomologous end joining [GO:0006303]; establishment of protein-containing complex localization to telomere [GO:0097695]; establishment of RNA localization to telomere [GO:0097694]; female meiotic nuclear division [GO:0007143]; heart development [GO:0007507]; histone mRNA catabolic process [GO:0071044]; histone phosphorylation [GO:0016572]; intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630]; lipoprotein catabolic process [GO:0042159]; male meiotic nuclear division [GO:0007140]; meiotic telomere clustering [GO:0045141]; mitotic G2 DNA damage checkpoint signaling [GO:0007095]; mitotic spindle assembly checkpoint signaling [GO:0007094]; multicellular organism growth [GO:0035264]; negative regulation of B cell proliferation [GO:0030889]; negative regulation of telomere capping [GO:1904354]; negative regulation of TORC1 signaling [GO:1904262]; neuron apoptotic process [GO:0051402]; oocyte development [GO:0048599]; ovarian follicle development [GO:0001541]; peptidyl-serine autophosphorylation [GO:0036289]; peptidyl-serine phosphorylation [GO:0018105]; positive regulation of apoptotic process [GO:0043065]; positive regulation of cell adhesion [GO:0045785]; positive regulation of cell migration [GO:0030335]; positive regulation of DNA catabolic process [GO:1903626]; positive regulation of DNA damage response, signal transduction by p53 class mediator [GO:0043517]; positive regulation of gene expression [GO:0010628]; positive regulation of histone phosphorylation [GO:0033129]; positive regulation of neuron apoptotic process [GO:0043525]; positive regulation of telomerase catalytic core complex assembly [GO:1904884]; positive regulation of telomere maintenance via telomerase [GO:0032212]; positive regulation of telomere maintenance via telomere lengthening [GO:1904358]; positive regulation of transcription by RNA polymerase II [GO:0045944]; post-embryonic development [GO:0009791]; pre-B cell allelic exclusion [GO:0002331]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; reciprocal meiotic recombination [GO:0007131]; regulation of apoptotic process [GO:0042981]; regulation of autophagy [GO:0010506]; regulation of cell cycle [GO:0051726]; regulation of cellular response to gamma radiation [GO:1905843]; regulation of cellular response to heat [GO:1900034]; regulation of microglial cell activation [GO:1903978]; regulation of signal transduction by p53 class mediator [GO:1901796]; regulation of telomere maintenance via telomerase [GO:0032210]; replicative senescence [GO:0090399]; response to hypoxia [GO:0001666]; response to ionizing radiation [GO:0010212]; signal transduction [GO:0007165]; somitogenesis [GO:0001756]; telomere maintenance [GO:0000723]; thymus development [GO:0048538]; V(D)J recombination [GO:0033151] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D868G	TCGA-AX-A1C9	UCEC	TCGA	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1111
p.D868G	DO43098	UCEC	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1111
p.D863G	TCGA-BG-A222	UCEC	TCGA	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.25
p.D863G	DO42977	UCEC	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.25
p.S867T	TCGA-CC-A3MB	LIHC	TCGA	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1389
p.S867T	DO23068	LIHC	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1389
p.D863N	TCGA-XF-AAML	BLCA	TCGA	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.25
p.D863N	DO51933	BLCA	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.25
p.A869V	DO230342	COCA	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.0833
p.E848D	DO223045	ESCA	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1389
p.F858S	DO225438	LAML	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation altering degron motif	0.7982
p.E850D	DO228948	LICA	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1944
p.D860N	DO227684	PACA	ICGC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation altering degron motif	0.6932
p.E848Q	SIDM00708	Non-Small Cell Lung Carcinoma	GDSC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1389
p.E848Q	ACH-000841	Lung Cancer	CCLE	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1389
p.E848Q	NCI-H2087	lung	COSMIC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation rewiring degron network	0.1389
p.L857V	SIDM01569	Hepatocellular Carcinoma	GDSC	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation altering degron motif	0.5654
p.L857V	ACH-000734	Liver Cancer	CCLE	MNLFND	LIG_APCC_ABBA_1	855:860	Mutation altering degron motif	0.5654

DegronMD: protein-targeted degradation, mutation and drug response to degrons

ATM

UniProt ID: Q13315

Entrez ID: 472

Protein name: Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for ATM in