ATM signaling (Homo sapiens)

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PStructural change of ChromatinInactiveDimerMDMX Ubiquitination &DegradationDNARepairIR RadiationCell CycleCheckpointControlCellSurvivalPPPPPPPPPPPPPPPCellSurvivalPSynaptic VesicleTransportNegative regulationof S phaseSAPK(MAPK9)CDC25CTP73H2AXDNA repairBIDRAD51TP53BRCA1p21ATMDNA repair& RecombinationG2/M transitionCyclin BMDM2Negative regulation ofG2/M transitionc-AblTP53BP1DNA repairTLK1SenescenceChk1RAD50S Phase ofMitotic Cell CyleCell CycleCheckpointActivationIKBACREB1ATF2Apoptosisc-JunRAD9AChk2ApoptosisMDC1NF kappa B PathwayCDC25ACDK1MRE11MDMX(MDM4)AP3B2CDC2DNA DamageCDK2SMC1AGADD45AFANCD2NBS11-6S Phase of MitoticCell CyleMRE11RAD50NBS1ATMATM1-6ATM1-61-6


Description

ATM (for Ataxia-telangiectasia mutated) has been located by restriction-fragment length polymorphism in the chromosomal region 11q22-23. Interestingly, the site of ATM is the same or adjacent to the region occupied by CD3 (Antigen, Delta subunit), THY1 (T-Cell antigen), and NCAM (Cell Adhesion Molecule, Neural, 1) genes, all of which are members of the immunoglobulin-gene superfamily and consequently may be subject to the same defect that afflicts the T-cell receptor and immunoglobulin molecules in A-T. The ATM gene presents an open reading frame (ORF) of 9,165 kb cDNA and is constituted by 66 exons spread over 150 kb of genomic DNA which has a transcript of 12 kb. The ORF of this transcript predicts a 370-kDa protein composed of 3056 amino acids. Over 300 mutations have been found in A-T patients, distributed across the full length (150 kb of genomic DNA) of the ATM gene.

Sequence homology indicates that the atm gene product falls into a family of proteins that are related to the catalytic subunit of phosphatidylinositol 3-kinase (PI 3-kinase). This family includes TEL1, MEC1, TOR1, and TOR2 of the budding yeast Saccharomyces cerevisiae, RAD3 of the fission yeast Schizosaccharomyces pombe, and MEI-41 of Drosophila melanogaster. The mammalian family member most closely related to ATM is the ATR/FRP1 protein and, like its yeast homologs, it mediates cellular responses to unreplicated or damaged DNA. In humans the PI 3-kinase family includes the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) and FRAP. These sequence homologies appear to reflect functional homology because many of the PI 3-kinase family members are involved in DNA repair, recombination and cell cycle control. Despite the resemblance to lipid kinases, members of this family, including ATM, possess a serine/threonine protein kinase activity, which is wortmannin sensitive.

ATM phosphoprotein is ubiquitously expressed and predominantly found in nuclei of proliferating cells, but subcellular fractionation and immunofluorescence revealed that 10-20% of the protein is present in cytoplasmic vesicles, including peroxisomes and endosomes and a prominent cytoplasmic fraction in mouse oocytes. ATM is endosome-bound in mouse neurons, suggesting molecular sorting of the protein

occurs in the cytoplasm. In Purkinje cells, distribution of ATM protein is primarily in cytoplasm, and this may be related to the differentiation state of the cells. ATM mRNA is present in all human and mouse tissues. In situ hybridization shows that ATM mRNA is expressed throughout the whole mouse embryo. Furthermore, ATM has been associated with β-adaptin in lymphoblast vesicles indicating that it may play a role in intracellular vesicle and/or protein transport mechanisms. No obvious nuclear localization signals have been detected in ATM. Neither an ectopically expressed N-terminal fragment of the protein nor a C-terminal fragment is capable of entering the nucleus.

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History

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CompareRevisionActionTimeUserComment
129687view00:47, 22 May 2024EweitzModified title
128135view14:20, 27 January 2024EweitzUse standard order of graphics and labels in legend
128134view14:18, 27 January 2024EweitzUpgrade legend
128133view14:10, 27 January 2024EweitzStandardize case
116808view10:11, 14 May 2021EweitzModified title
115323view09:15, 13 February 2021EgonwMade several pathways clickable
102220view20:49, 11 December 2018Khanspersswitched multiple interactions to segmented
102213view00:14, 11 December 2018Khanspersconverted ineractions to graphical lines in legend
90247view21:13, 26 October 2016AmanzoModification of some titles
90241view17:50, 26 October 2016AmanzoModification on titles of some paths
90240view17:29, 26 October 2016AmanzoPeriodical save, work in progress
84490view23:16, 25 February 2016KhanspersQuick edit to datanode annotation or property
81224view23:13, 5 August 2015AlexanderPicoremoving final IE-incompatible character
81223view22:54, 5 August 2015AlexanderPicoremoving more IE-incompatible character
81218view19:15, 5 August 2015AlexanderPicoremoving IE-incompatible character
79964view14:04, 28 April 2015ZariChanged Id UniProt to Entrez gene for CDC2
78531view10:30, 7 January 2015MaintBotadded missing graphIds
76317view06:53, 2 July 2014MkutmonFixed datasource of S Phase Arrest pathway datanode
72241view18:46, 29 October 2013Khanspersadded one more WP node
72240view18:45, 29 October 2013Khansperschanged pathway node xrefs from GO to WP
71697view19:44, 17 October 2013MaintBotUpdated data sources
70531view16:44, 9 August 2013AmanzoWork in progress
70530view16:42, 9 August 2013AmanzoPeriodical save, work in progress
70529view16:11, 9 August 2013AmanzoPeriodical save, work in progress
70528view16:01, 9 August 2013AmanzoPeriodical save, work in progress
70527view15:50, 9 August 2013AmanzoPeriodical save, work in progress
70458view22:04, 3 August 2013AmanzoPeriodical save, work in progress
70457view21:54, 3 August 2013AmanzoPeriodical save, work in progress
70446view19:05, 1 August 2013AmanzoPeriodical save, work in progress
70445view18:55, 1 August 2013AmanzoPeriodical save, work in progress
70444view18:44, 1 August 2013AmanzoPeriodical save, work in progress
70085view15:44, 12 July 2013AmanzoModified description
70084view15:33, 12 July 2013Amanzowork in progress
70083view15:31, 12 July 2013AmanzoIR figure fixed
70082view15:27, 12 July 2013AmanzoPeriodical save, work in progress
70081view15:13, 12 July 2013AmanzoPeriodical save, work in progress
70072view09:01, 12 July 2013Mkutmonreplaced interaction lines in radiation figure with graphical lines
70004view23:12, 11 July 2013AmanzoModified description
70003view23:11, 11 July 2013AmanzoModified description
70002view23:08, 11 July 2013AmanzoWork in progress
70000view22:57, 11 July 2013AmanzoPeriodical save, work in progress
69999view22:47, 11 July 2013AmanzoPeriodical save, work in progress
69998view22:36, 11 July 2013AmanzoPeriodical save, work in progress
69706view22:54, 9 July 2013AmanzoReferences added
69705view22:49, 9 July 2013AmanzoPeriodical save, work in progress
69704view22:39, 9 July 2013AmanzoPeriodical save, work in progress
69703view22:35, 9 July 2013Amanzowork in progress
69702view22:10, 9 July 2013AmanzoPeriodical save, work in progress
69701view21:59, 9 July 2013AmanzoPeriodical save, work in progress
69698view19:10, 9 July 2013AmanzoPeriodical save, work in progress

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AP3B2ProteinQ13367 (Uniprot/TrEMBL)
ATF2GeneProductENSG00000115966 (Ensembl)
ATMGeneProductENSG00000149311 (Ensembl)
ApoptosisPathwayGO:0008630 (GeneOntology)
ApoptosisPathwayGO:0042771 (GeneOntology)
BIDProteinP55957 (Uniprot/TrEMBL)
BRCA1ProteinP38398 (Uniprot/TrEMBL)
CDC25AGeneProductENSG00000164045 (Ensembl)
CDC25CGeneProductENSG00000158402 (Ensembl)
CDC2GeneProductI6L9I5 (Uniprot/TrEMBL)
CDK1GeneProductENSG00000170312 (Ensembl)
CDK2ProteinP24941 (Uniprot/TrEMBL)
CREB1GeneProduct1385 (Entrez Gene)
Cell Cycle

Checkpoint

Activation		PathwayGO:0000075 (GeneOntology)
Chk1ProteinO14757 (Uniprot/TrEMBL)
Chk2ProteinO96017 (Uniprot/TrEMBL)
Cyclin BGeneProduct891 (Entrez Gene)
DNA DamagePathwayGO:0042770 (GeneOntology)
DNA repair & RecombinationPathwayGO:0006281 (GeneOntology)
DNA repairPathwayGO:0006281 (GeneOntology)
FANCD2ProteinQ9BXW9 (Uniprot/TrEMBL)
G2/M transitionPathwayGO:0000086 (GeneOntology)
GADD45AGeneProduct1647 (Entrez Gene)
H2AXProteinP16104 (Uniprot/TrEMBL)
IKBAProteinP25963 (Uniprot/TrEMBL)
MDC1ProteinQ14676 (Uniprot/TrEMBL)
MDM2ProteinQ00987 (Uniprot/TrEMBL)
MDMX (MDM4)GeneProductO15151 (Uniprot/TrEMBL)
MRE11ProteinP49959 (Uniprot/TrEMBL)
NBS1ProteinO60934 (Uniprot/TrEMBL)
NF kappa B PathwayPathwayko04064 (KEGG Pathway)
Negative regulation of S phasePathwayGO:0045749 (GeneOntology)
Negative regulation of G2/M transitionPathwayGO:0010972 (GeneOntology)
RAD50ProteinQ92878 (Uniprot/TrEMBL)
RAD51GeneProductENSG00000051180 (Ensembl)
RAD9AGeneProductENSG00000172613 (Ensembl)
S Phase of Mitotic Cell CylePathwayGO:0000084 (GeneOntology)
S Phase of Mitotic Cell CylePathwayGO:0000084 (GeneOntology)
SAPK (MAPK9)GeneProductENSG00000050748 (Ensembl)
SMC1AProteinQ14683 (Uniprot/TrEMBL)
SenescencePathwayGO:0090400 (GeneOntology)
TLK1ProteinQ9UKI8 (Uniprot/TrEMBL)
TP53BP1GeneProductENSG00000067369 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
TP73GeneProductENSG00000078900 (Ensembl)
c-AblGeneProductENSG00000097007 (Ensembl)
c-JunGeneProductENSG00000177606 (Ensembl)
p21GeneProductENSG00000124762 (Ensembl)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2516"
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