Identifiers
Ataxia telangiectasia mutated
HUGO:ATM HGNC:795 ENTREZ:472 UNIPROT:Q13315 GENECARDS:ATM REACTOME:85553 KEGG:472 ATLASONC:ATM123 WIKI:ATM
ATA “ataxia telangiectasia mutated (includes complementation groups A C and D)” ATC ATD ATDC
Maps_Modules
EMT / EMT_REGULATORS
Apoptosis / MITOCH_METABOLISM
DNA repair / G1_S_CHECKPOINT
DNA repair / S_PHASE_CHECKPOINT
DNA repair / G2_M_CHECKPOINT
Cell cycle / APOPTOSIS_ENTRY
Cell cycle / CYCLINB
Cell cycle / E2F1
Survival / MAPK
References
MDM2 phosphorylation by ATM inhibits its interaction with p53
PMID:15140942
Phosphorylation at Ser395
PMID:11331603
DDR by ATM
PMID:23847781
PMID:17303408, PMID:16163361, PMID:15964794
For S-phase checkpoint
PMID:15459660, PMID:12607003, PMID:11877377
ATM@Nucleus
References
e_re1210( EMT ):
MDM2 phosphorylation by ATM inhibits its interaction with p53
PMID:15140942
Phosphorylation at Ser395
PMID:11331603
ATM|S1981_unk|K3016_unk@Nucleus
References
a_re1239:( Apoptosis ) reactionType:is.a
a_re1241( Apoptosis ):
hierarchical:post-MOMP
reactionType:casp.cleavage
PMID:10454555
in HL60
in vitro
ATM|hm2@Site of DNA damage
References
a_re1485( Apoptosis ):
influenceDelete: re to reactants
PMID:17486112
by NBN
a_re1510:( Apoptosis ) reactionType:is.a
ATM|S1981_pho|K3016_ace@Site of DNA damage
References
a_re1046( Apoptosis ):
PMID:12234250
in G361 human melanoma cells, upon ionizing radiations
in vitro by ATM and DNAPK
in Hela, ectopically expressed LKB1 T366-phosphorylated is located in the nucleus
PMID:20160076
in HeLa S3 cells that lack functional LKB1, reexpression of wild-type but not T366A LKB1 restored the ability to repress mTORC1 in response to H2O2
in MCF7, LKB1 is located in the cytoplasm, together with a proportion of ATM. H2O2 induces phosphorylation of cytoplasmic LKB1, but not other DNA damaging agents (etoposide). This supports a possible H2O2-induced and DNA damage-independent activation of the cytoplasmic of ATM responsible for LKB1 phosphorylation.
a_re1240:( Apoptosis ) reactionType:is.a
a_re1480( Apoptosis ):
PMID:18001824
PMID:18006705
a_re1488( Apoptosis ):
influenceDelete: re to reactants
PMID:9488723
PMID:11571274
ATM|hm2@Nucleus
References
a_re1239:( Apoptosis ) reactionType:is.a
a_re1485( Apoptosis ):
influenceDelete: re to reactants
PMID:17486112
by NBN
ATM|pho|S367_pho|S1893_pho|active@default
References
d_re36( DNA repair ):
PMID:16332722
Auto-phosphorylation of ATM in response to DNA DSB:
PMID:17303408, PMID:12556884, PMID:16858402
Amplification of ATM auto-phosphorylation by the complex ATM:MRNcomplex:H2AX:MDC1CDK5 phosphorylates and activates ATM
PMID:19151707
d_re32:( DNA repair ) PMID:19788416, PMID:9168117, PMID:11804596
d_re33:( DNA repair ) PMID:15485915
d_re43:( DNA repair ) PMID:16731533
d_re71( DNA repair ):
For inactivation of EXO1 by 53BP1-mediated phosphorylation:
PMID:18756267, PMID:15867354
ATM and ATR phosphorylate EXO1 and lead to EXO1 ubiquitination and degradation:
PMID:18048416, PMID:11438669, PMID:20019063
d_re82:( DNA repair ) PMID:21376743
d_re97:( DNA repair ) PMID:17303408, PMID:16163361, PMID:15964794
d_re110( DNA repair ):
Phosphorylation by ATM and ATR at T847, S327
Phosphorylation at S327 by ATM and ATR are essential for shift from A_NHEJ to HR
Phosphorylation by CDC2(CDK1) in cell cycle dep manner to shift from C_NHEJ ot HR at: Ser 267
This phosphorylation allows resection that initiates HR and blocks binding of Ku70/Ku80 complex that initiates C_NHEJ.
PMID:19357644, PMID:15485915, PMID:19490890, PMID:18716619 (for CDK-dep phosph), PMID:20051983
BRCA1 and CtIP interactions make shift from A_NHEJ and C_NHEJ toward HR
Resected DNA in HR is a positive trigger for amplification of the HR pathway (positive loop):
PMID:20051983
Only when CDKs are fully active, this fully activates HR during S and G2 phases:
PMID:18511906, PMID:18716619
d_re115( DNA repair ):
PMID:16581787,
For inhibition of S-checkpoint by ATM:
PMID:15175241
Inhibition of Sphase by MRE complex:
PMID:17713585
By CycE*/CDK2: G1/S transition
By CycD*/CDK2/CIp/KIP: checkpoint G1/S
d_re119( DNA repair ):
PMID:15175241, PMID:12086603
For inhibition of S-checkpoint by HCLK2/FAAP24/ATR/FANKM complex:
PMID:19282663, PMID:19622404, PMID:18995830
For interaction between SNM1B and ATM to mediate S-phase checkpoint in response to ICL (intra-chromatide lesion):
PMID:18469862
Resected DNA is a triger for activating the S-phase checkpoint and moving from G1 to S to G2:
PMID:20051983, PMID:16805667
For inhibition of S to G2 propagation and activation of S-phase checkpoint by complex PCNA:CtIP:
PMID:19342888
ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. O6-methylguanine adducts recognized by MutSalpha, MutLalpha and BER pathways performs the repair. ATR/ATRIP S phase arrest is activated:
PMID:16713580
For role of TIM1*/TIPIN in S-phase checkpoint, stalled replication forks stabilisation and DNA repair during S-phase:
PMID:17102137, PMID:17116885, PMID:17296725, PMID:19793801, PMID:17582221
For inhibition of S-phase by ATR/ATRIP/CHEK1/CLSPN/HCLK2* complex:
PMID:19793801, PMID:17384638
For ATR/ATRIP/CHEK1/Tim* S-phase checkpoint
PMID:15798197
Formation of the complex for crosslink-activation of S phase checkpoint. FA core complex activates the reaction to stop S-phase propagaton:
PMID:14988723, PMID:15136767
d_re132:( DNA repair ) PMID:19841479, PMID:19793861
d_re148( DNA repair ):
PMID:18006705
PMID:18583988
d_re198( DNA repair ):
ATM phosphotylates FANCD2 for S-phase checkpoint arrest in responce to IR.
PMID:12086603
d_re408:( DNA repair ) PMID:9858600
ATM@default
References
d_re36( DNA repair ):
PMID:16332722
Auto-phosphorylation of ATM in response to DNA DSB:
PMID:17303408, PMID:12556884, PMID:16858402
Amplification of ATM auto-phosphorylation by the complex ATM:MRNcomplex:H2AX:MDC1CDK5 phosphorylates and activates ATM
PMID:19151707
ATM|Ser 1981_pho@Nucleus
References
c_re141( Cell cycle ):
PMID:15829956, PMID:15140942
Auto-phosphorylation catalysed by E2F1
PMID:15024084
Autophosphorylation of ATM within dimeric ATM complexes
PMID:12556884
c_re158( Cell cycle ):
MDM2 phosphorylation by ATM inhibits its interaction with p53
PMID:15140942
Phosphorylation at Ser395
PMID:11331603
c_re159:( Cell cycle ) PMID:12814430, PMID:12861053
c_re622( Cell cycle ):
Upon DNA damage, E2F is stabilized by ATM phosphorylation.
PMID:15838517, PMID:15140942
14-3-3 tau mediates E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. 14-3-3 tau is also required for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and caspases, during DNA damage.
PMID:15494392
ATM@Cytoplasm
References
s_mpk1_re179( Survival ):
P53 is a nuclear P38 target.
Activated P38 phosphorylates P53 at several residues including Ser33 and thereby increases the transcriptional activity of P53.
ATM phosphorylates P53 at ser15 and stabilize it.
PMID:20506250 PMID:21614932 PMID:15140942
s_mpk1_re255( Survival ):
Ataxia telangiectasia mutated (ATM) is activated in response to DNA damage and directly phosphorylates TAOK.
PMID:18855897
Modifications:
In compartment: Cytoplasm
In compartment: Nucleus
In compartment: Site of DNA damage
In compartment: default
Participates in complexes:
In compartment: Nucleus
- ATM|Ser 1981_pho:NBS1*|pho@Nucleus
- ATM|pho|S367_pho|S1893_pho:CTIP*|emp:NBS1*|S343_pho:WRN@Nucleus
In compartment: default
- ATM|pho|S367_pho|S1893_pho:SNM1B*@default
- ATM|pho|S367_pho|S1893_pho:MRE11*:NBS1*|S343_pho:RAD50@default
- ATM|pho|S367_pho|S1893_pho:H2AFX|pho|ubi:MDC1|pho:MRE11*:NBS1*|S343_pho:RAD50@default
Participates in reactions:
As Reactant or Product:
- ATM|hm2@Nucleus
→
ATM|S1981_unk|K3016_unk@Nucleus
- ATM|S1981_pho|K3016_ace@Site of DNA damage
→
ATM|S1981_unk|K3016_unk@Nucleus
- ATM|S1981_unk|K3016_unk@Nucleus
→
cleaved~ATM*@Site of DNA damage
- ATM|hm2@Nucleus
→
ATM|hm2@Site of DNA damage
- ATM|hm2@Site of DNA damage
→
ATM|S1981_pho|K3016_ace@Site of DNA damage
- ATM|S1981_pho|K3016_ace@Site of DNA damage
→
ATM|hm2@Site of DNA damage
- ATM|hm2@Site of DNA damage
→
ATM|S1981_unk|K3016_unk@Nucleus
- ATM@Nucleus
→
ATM|Ser 1981_pho@Nucleus
- ATM|Ser 1981_pho@Nucleus
+ NBS1*|pho@Nucleus
→
ATM|Ser 1981_pho:NBS1*|pho@Nucleus
- ATM|pho|S367_pho|S1893_pho:MRE11*:NBS1*|S343_pho:RAD50@default
+ CTIP*|emp@default
+ WRN@Nucleus
→
ATM|pho|S367_pho|S1893_pho:CTIP*|emp:NBS1*|S343_pho:WRN@Nucleus
- ATM|pho|S367_pho|S1893_pho|active@default
+ SNM1B*@default
→
ATM|pho|S367_pho|S1893_pho:SNM1B*@default
- ATM@default
→
ATM|pho|S367_pho|S1893_pho|active@default
- ATM|pho|S367_pho|S1893_pho:MRE11*:NBS1*|S343_pho:RAD50@default
+ H2AFX|pho|ubi:MDC1|pho@default
→
ATM|pho|S367_pho|S1893_pho:H2AFX|pho|ubi:MDC1|pho:MRE11*:NBS1*|S343_pho:RAD50@default
- ATM|pho|S367_pho|S1893_pho|active@default
+ MRE11*:NBS1*|S343_pho:RAD50@default
→
ATM|pho|S367_pho|S1893_pho:MRE11*:NBS1*|S343_pho:RAD50@default
As Catalyser:
- STK11|K48_unk@Nucleus
→
STK11|K48_unk|T366_pho@Nucleus
- p53*@Nucleus
→
p53*|S15_pho|active@Nucleus
- MDC1|Nter-SDT-motifs_pho@Site of DNA damage
→
MDC1|T752_pho|T699_pho|T719_pho|Nter-SDT-motifs_pho@Site of DNA damage
- H2AFX@Nucleus
→
H2AFX|S139_pho@Site of DNA damage
- CHEK2@Nucleus
→
CHEK2|Thr68_pho@Nucleus
- p53*@Nucleus
→
p53*|Ser15_pho@Nucleus
- ATM@Nucleus
→
ATM|Ser 1981_pho@Nucleus
- MDM2@Nucleus
→
MDM2|S395_pho@Nucleus
- NBS1*@Nucleus
→
NBS1*|pho@Nucleus
- DP1*:E2F1|Lys_ace:PCAF*@Nucleus
→
DP1*:E2F1|Lys_ace|Ser31_pho@Nucleus
+ PCAF*@Nucleus
- gA_NHEJ_DNA_st1*@Nucleus
→
gA_NHEJ_DNA_st2*@Nucleus
- CTIP*|emp@default
→
CTIP*|emp|S372_pho|T847_pho|S267_pho@default
- gHR_DNA_st1*@Nucleus
→
gHR_DNA_st2*@Nucleus
- G1 phase@default
→
S phase@default
- S phase@default
→
G2 phase@default
- G2 phase@default
→
M phase@default
- SMARCAL1@default
→
SMARCAL1|pho@default
- MDC1@default
→
MDC1|pho@default
- FANCD2@default
→
FANCD2|S222_pho@default
- ABL1@default
→
ABL1|S465_pho|active@default
- CHEK1@default
→
CHEK1|pho|active@default
- ATM@default
→
ATM|pho|S367_pho|S1893_pho|active@default
- CTBP*@default
→
CTBP*|S181_pho|T179_pho|S185_pho@default
- BRCA1@default
→
BRCA1|S988_pho|S1387_pho|S1423_pho|S1497_pho|S1524_pho|active@default
- PARP1@Nucleus
→
PARP1|PolyADPribose_unk|pho@Nucleus
- RPA2@default
→
RPA2|pho@default
- SMC1*@default
→
SMC1*|S957_pho|S966_pho@default
- SMC3@default
→
SMC3|S1083_pho@default
- SCC1*:SMC1*:SMC3:STAG*@default
→
SCC1*|ATM-dep._pho:SMC1*|S957_pho:SMC3|S1083_pho:STAG*@default
- MDM2@default
→
MDM2|pho@default
- SIAH*@default
→
SIAH*|pho@default
- PARP2@default
→
PARP2|unk|pho@default
- EXO1@default
→
EXO1|S692_pho|S372_pho|S567_pho|S587_pho@default
- CHEK2@default
→
CHEK2|pho|active@default
- Ku70*@default
+ Ku80*@default
→
Ku70*:Ku80*@Nucleus
- DNA-PK*@default
→
DNA-PK*|pho@default
- H2AFX@default
→
H2AFX|pho@default
- MDM2@Nucleus
→
MDM2|S395_pho@Nucleus
- p53*@Nucleus
→
p53*|pho@Nucleus
- TAOK*@Cytoplasm
→
TAOK*|pho@Cytoplasm