Protein ATM

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

1. ATM@Cytoplasm

In compartment: Nucleus

1. ATM@Nucleus

2. ATM|​hm2@Nucleus
3. ATM|​Ser 1981_pho@Nucleus
4. ATM|​S1981_unk|​K3016_unk@Nucleus

In compartment: Site of DNA damage

1. ATM|​hm2@Site of DNA damage

2. ATM|​S1981_pho|​K3016_ace@Site of DNA damage

In compartment: default

1. ATM@default

2. ATM|​pho|​S367_pho|​S1893_pho|​active@default

Participates in complexes:
In compartment: Nucleus

1. ATM|​Ser 1981_pho:​NBS1*|​pho@Nucleus

2. ATM|​pho|​S367_pho|​S1893_pho:​CTIP*|​emp:​NBS1*|​S343_pho:​WRN@Nucleus

In compartment: default

1. ATM|​pho|​S367_pho|​S1893_pho:​SNM1B*@default

2. ATM|​pho|​S367_pho|​S1893_pho:​MRE11*:​NBS1*|​S343_pho:​RAD50@default
3. ATM|​pho|​S367_pho|​S1893_pho:​H2AFX|​pho|​ubi:​MDC1|​pho:​MRE11*:​NBS1*|​S343_pho:​RAD50@default

Participates in reactions:
As Reactant or Product:

1. ATM|​hm2@Nucleus → ATM|​S1981_unk|​K3016_unk@Nucleus

2. ATM|​S1981_pho|​K3016_ace@Site of DNA damage → ATM|​S1981_unk|​K3016_unk@Nucleus
3. ATM|​S1981_unk|​K3016_unk@Nucleus → cleaved~ATM*@Site of DNA damage
4. ATM|​hm2@Nucleus → ATM|​hm2@Site of DNA damage
5. ATM|​hm2@Site of DNA damage → ATM|​S1981_pho|​K3016_ace@Site of DNA damage
6. ATM|​S1981_pho|​K3016_ace@Site of DNA damage → ATM|​hm2@Site of DNA damage
7. ATM|​hm2@Site of DNA damage → ATM|​S1981_unk|​K3016_unk@Nucleus
8. ATM@Nucleus → ATM|​Ser 1981_pho@Nucleus
9. ATM|​Ser 1981_pho@Nucleus + NBS1*|​pho@Nucleus → ATM|​Ser 1981_pho:​NBS1*|​pho@Nucleus
10. 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
11. ATM|​pho|​S367_pho|​S1893_pho|​active@default + SNM1B*@default → ATM|​pho|​S367_pho|​S1893_pho:​SNM1B*@default
12. ATM@default → ATM|​pho|​S367_pho|​S1893_pho|​active@default
13. 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
14. 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:

1. STK11|​K48_unk@Nucleus → STK11|​K48_unk|​T366_pho@Nucleus

2. p53*@Nucleus → p53*|​S15_pho|​active@Nucleus
3. MDC1|​Nter-SDT-motifs_pho@Site of DNA damage → MDC1|​T752_pho|​T699_pho|​T719_pho|​Nter-SDT-motifs_pho@Site of DNA damage
4. H2AFX@Nucleus → H2AFX|​S139_pho@Site of DNA damage
5. CHEK2@Nucleus → CHEK2|​Thr68_pho@Nucleus
6. p53*@Nucleus → p53*|​Ser15_pho@Nucleus
7. ATM@Nucleus → ATM|​Ser 1981_pho@Nucleus
8. MDM2@Nucleus → MDM2|​S395_pho@Nucleus
9. NBS1*@Nucleus → NBS1*|​pho@Nucleus
10. DP1*:​E2F1|​Lys_ace:​PCAF*@Nucleus → DP1*:​E2F1|​Lys_ace|​Ser31_pho@Nucleus + PCAF*@Nucleus
11. gA_NHEJ_DNA_st1*@Nucleus → gA_NHEJ_DNA_st2*@Nucleus
12. CTIP*|​emp@default → CTIP*|​emp|​S372_pho|​T847_pho|​S267_pho@default
13. gHR_DNA_st1*@Nucleus → gHR_DNA_st2*@Nucleus
14. G1 phase@default → S phase@default
15. S phase@default → G2 phase@default
16. G2 phase@default → M phase@default
17. SMARCAL1@default → SMARCAL1|​pho@default
18. MDC1@default → MDC1|​pho@default
19. FANCD2@default → FANCD2|​S222_pho@default
20. ABL1@default → ABL1|​S465_pho|​active@default
21. CHEK1@default → CHEK1|​pho|​active@default
22. ATM@default → ATM|​pho|​S367_pho|​S1893_pho|​active@default
23. CTBP*@default → CTBP*|​S181_pho|​T179_pho|​S185_pho@default
24. BRCA1@default → BRCA1|​S988_pho|​S1387_pho|​S1423_pho|​S1497_pho|​S1524_pho|​active@default
25. PARP1@Nucleus → PARP1|​PolyADPribose_unk|​pho@Nucleus
26. RPA2@default → RPA2|​pho@default
27. SMC1*@default → SMC1*|​S957_pho|​S966_pho@default
28. SMC3@default → SMC3|​S1083_pho@default
29. SCC1*:​SMC1*:​SMC3:​STAG*@default → SCC1*|​ATM-dep._pho:​SMC1*|​S957_pho:​SMC3|​S1083_pho:​STAG*@default
30. MDM2@default → MDM2|​pho@default
31. SIAH*@default → SIAH*|​pho@default
32. PARP2@default → PARP2|​unk|​pho@default
33. EXO1@default → EXO1|​S692_pho|​S372_pho|​S567_pho|​S587_pho@default
34. CHEK2@default → CHEK2|​pho|​active@default
35. Ku70*@default + Ku80*@default → Ku70*:​Ku80*@Nucleus
36. DNA-PK*@default → DNA-PK*|​pho@default
37. H2AFX@default → H2AFX|​pho@default
38. MDM2@Nucleus → MDM2|​S395_pho@Nucleus
39. p53*@Nucleus → p53*|​pho@Nucleus
40. TAOK*@Cytoplasm → TAOK*|​pho@Cytoplasm