ATM

Protein ATM map

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  map  / EMT_REGULATORS  map
 Apoptosis  map  / MITOCH_METABOLISM  map
 DNA repair  map  / G1_S_CHECKPOINT  map
 DNA repair  map  / S_PHASE_CHECKPOINT  map
 DNA repair  map  / G2_M_CHECKPOINT  map
 Cell cycle  map  / APOPTOSIS_ENTRY  map
 Cell cycle  map  / CYCLINB  map
 Cell cycle  map  / E2F1  map
 Survival  map  / MAPK  map

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  map ):
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  map ) reactionType:is.a
a_re1241( Apoptosis  map ):
hierarchical:post-MOMP
reactionType:casp.cleavage
PMID:10454555
in HL60
in vitro

ATM|​hm2@Site of DNA damage

References
a_re1485( Apoptosis  map ):
influenceDelete: re to reactants
PMID:17486112
by NBN
a_re1510:( Apoptosis  map ) reactionType:is.a

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

References
a_re1046( Apoptosis  map ):
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  map ) reactionType:is.a
a_re1480( Apoptosis  map ):
PMID:18001824
PMID:18006705
a_re1488( Apoptosis  map ):
influenceDelete: re to reactants
PMID:9488723
PMID:11571274

ATM|​hm2@Nucleus

References
a_re1239:( Apoptosis  map ) reactionType:is.a
a_re1485( Apoptosis  map ):
influenceDelete: re to reactants
PMID:17486112
by NBN

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

References
d_re36( DNA repair  map ):
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  map ) PMID:19788416, PMID:9168117, PMID:11804596
d_re33:( DNA repair  map ) PMID:15485915
d_re43:( DNA repair  map ) PMID:16731533
d_re71( DNA repair  map ):
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  map ) PMID:21376743
d_re97:( DNA repair  map ) PMID:17303408, PMID:16163361, PMID:15964794
d_re110( DNA repair  map ):
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  map ):
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  map ):
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  map ) PMID:19841479, PMID:19793861
d_re148( DNA repair  map ):
PMID:18006705
PMID:18583988
d_re198( DNA repair  map ):
ATM phosphotylates FANCD2 for S-phase checkpoint arrest in responce to IR.
PMID:12086603
d_re408:( DNA repair  map ) PMID:9858600

ATM@default

References
d_re36( DNA repair  map ):
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  map ):
PMID:15829956, PMID:15140942
Auto-phosphorylation catalysed by E2F1
PMID:15024084
Autophosphorylation of ATM within dimeric ATM complexes
PMID:12556884
c_re158( Cell cycle  map ):
MDM2 phosphorylation by ATM inhibits its interaction with p53
PMID:15140942
Phosphorylation at Ser395
PMID:11331603
c_re159:( Cell cycle  map ) PMID:12814430, PMID:12861053
c_re622( Cell cycle  map ):
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  map ):
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  map ):
Ataxia telangiectasia mutated (ATM) is activated in response to DNA damage and directly phosphorylates TAOK.
PMID:18855897


Modifications:
In compartment: Cytoplasm
  1. ATM@Cytoplasm map

In compartment: Nucleus

  1. ATM@Nucleus map

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

In compartment: Site of DNA damage

  1. ATM|​hm2@Site of DNA damage map

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

In compartment: default

  1. ATM@default map

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

Participates in complexes:
In compartment: Nucleus

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

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

In compartment: default

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

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

Participates in reactions:
As Reactant or Product:

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

  2. ATM|​S1981_pho|​K3016_ace@Site of DNA damage map map ATM|​S1981_unk|​K3016_unk@Nucleus map
  3. ATM|​S1981_unk|​K3016_unk@Nucleus map map cleaved~ATM*@Site of DNA damage map
  4. ATM|​hm2@Nucleus map map ATM|​hm2@Site of DNA damage map
  5. ATM|​hm2@Site of DNA damage map map ATM|​S1981_pho|​K3016_ace@Site of DNA damage map
  6. ATM|​S1981_pho|​K3016_ace@Site of DNA damage map map ATM|​hm2@Site of DNA damage map
  7. ATM|​hm2@Site of DNA damage map map ATM|​S1981_unk|​K3016_unk@Nucleus map
  8. ATM@Nucleus map map ATM|​Ser 1981_pho@Nucleus map
  9. ATM|​Ser 1981_pho@Nucleus map + NBS1*|​pho@Nucleus map map ATM|​Ser 1981_pho:​NBS1*|​pho@Nucleus map
  10. ATM|​pho|​S367_pho|​S1893_pho:​MRE11*:​NBS1*|​S343_pho:​RAD50@default map + CTIP*|​emp@default map + WRN@Nucleus map map ATM|​pho|​S367_pho|​S1893_pho:​CTIP*|​emp:​NBS1*|​S343_pho:​WRN@Nucleus map
  11. ATM|​pho|​S367_pho|​S1893_pho|​active@default map + SNM1B*@default map map ATM|​pho|​S367_pho|​S1893_pho:​SNM1B*@default map
  12. ATM@default map map ATM|​pho|​S367_pho|​S1893_pho|​active@default map
  13. ATM|​pho|​S367_pho|​S1893_pho:​MRE11*:​NBS1*|​S343_pho:​RAD50@default map + H2AFX|​pho|​ubi:​MDC1|​pho@default map map ATM|​pho|​S367_pho|​S1893_pho:​H2AFX|​pho|​ubi:​MDC1|​pho:​MRE11*:​NBS1*|​S343_pho:​RAD50@default map
  14. ATM|​pho|​S367_pho|​S1893_pho|​active@default map + MRE11*:​NBS1*|​S343_pho:​RAD50@default map map ATM|​pho|​S367_pho|​S1893_pho:​MRE11*:​NBS1*|​S343_pho:​RAD50@default map

As Catalyser:

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

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

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