Reviewed,
UniProtKB/Swiss-Prot Q62388 (ATM_MOUSE)
Last modified
February 9, 2010.
Version 98.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Serine-protein kinase ATM EC=2.7.11.1 Alternative name(s): Ataxia telangiectasia mutated homolog Short name=A-T mutated homolog | ||
| Gene names |
| ||
| Organism | Mus musculus (Mouse) | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 3066 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Binds DNA ends. Plays a role in replication-dependent histone mRNA degradation By similarity. Ref.5 Ref.6 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Enzyme regulation | Inhibited by wortmannin By similarity. |
| Subunit structure | Dimers or tetramers in inactive state. On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active. Binds DNA ends, p53/TP53, ABL1, BRCA1, NBN/nibrin and TERF1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. DNA damage promotes association with RAD17. Interacts with EEF1E1; the interaction, induced on DNA damage, upregulates TP53. Interacts with DCLRE1C, MYST1, KAT5, OBFC2B, ATMIN and CEP164 By similarity. Interacts with AP2B1 AND AP3B2; the interaction occurs in cytoplasmic vesicles. Ref.4 |
| Subcellular location | Nucleus By similarity. Cytoplasmic vesicle By similarity. Note: Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin By similarity. Ref.2 |
| Tissue specificity | Expressed in brain, skeletal muscle, testis, followed by spleen, lung, kidney, heart, liver and thymus. Ubiquitously expressed in embryonal tissues. |
| Developmental stage | Highest expression in embryonic central nervous system, from E13.5 day and during the whole cerebellar development. Decreased expression when maturation occurs. Ref.3 |
| Domain | The FATC domain is required for interaction with KAT5 By similarity. |
| Post-translational modification | Phosphorylated by NUAK1/ARK5 By similarity. Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase. Acetylated by KAT5 upon DNA damage; which is required for autophosphorylation and subsequent activation By similarity. |
| Involvement in disease | Atm-deficient mice show a phenotype similar to human ataxia telangiectasia (AT) and consistently develop immature T-cells malignancies. Ref.6 |
| Sequence similarities | Belongs to the PI3/PI4-kinase family. ATM subfamily. Contains 1 FAT domain. Contains 1 FATC domain. Contains 1 PI3K/PI4K domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 3066 | 3066 | Serine-protein kinase ATM | PRO_0000088841 | |||||
Regions | |||||||||
| Domain | 1966 – 2576 | 611 | FAT | ||||||
| Domain | 2722 – 2972 | 251 | PI3K/PI4K | ||||||
| Domain | 3034 – 3066 | 33 | FATC | ||||||
| Region | 1380 – 1389 | 10 | Interaction with ABL1 By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 86 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 367 | 1 | Phosphoserine; by autocatalysis Ref.6 | ||||||
| Modified residue | 372 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 1889 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1899 | 1 | Phosphoserine; by autocatalysis Ref.6 | ||||||
| Modified residue | 1987 | 1 | Phosphoserine; by autocatalysis Ref.6 | ||||||
| Modified residue | 1991 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 3006 | 1 | Phosphoserine By similarity | ||||||
Experimental info | |||||||||
| Mutagenesis | 367 | 1 | S → A: Retains genomic stability and cell cycle checkpoint correction and kinase activity towards downstream targets; when associated with A-1987. Retains genomic stability, cell cycle checkpoint correction and kinase activity on downstream targets; when associated with A-1899 and A-1987. Ref.6 | ||||||
| Mutagenesis | 1899 | 1 | S → A: Retains genomic stability, cell cycle checkpoint correction and kinase activity on downstream targets; when associated with A-367 and A-1987. Ref.6 | ||||||
| Mutagenesis | 1987 | 1 | S → A: Retains genomic stability and cell cycle checkpoint correction and kinase activity towards downstream targets; when associated with A-367. Retains genomic stability, cell cycle checkpoint correction and kinase activity on downstream targets; when associated with A-367 and A-1987. Ref.6 | ||||||
Sequences
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References
| [1] | "Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene." Pecker I., Avraham K.B., Gilbert D.J., Savitsky K., Rotman G., Harnik R., Fukao T., Schroeck E., Hirotsume S., Tagle D.A., Collins F.S., Wynshaw-Boris A., Ried T., Copeland N.G., Jenkins N.A., Shiloh Y., Ziv Y. Genomics 35:39-45(1996) [PubMed: 8661102] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain. |
| [2] | "Analysis of the ATM protein in wild-type and ataxia telangiectasia cells." Lakin N.D., Weber P., Stankovic T., Rottinghaus S.T., Taylor A.M.R., Jackson S.P. Oncogene 13:2707-2716(1996) [PubMed: 9000145] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [3] | "Atm expression patterns suggest a contribution from the peripheral nervous system to the phenotype of ataxia-telangiectasia." Soares H.D., Morgan J.I., McKinnon P.J. Neuroscience 86:1045-1054(1998) [PubMed: 9697112] [Abstract] Cited for: DEVELOPMENTAL STAGE. Strain: B6C3-F1. |
| [4] | "ATM binds to beta-adaptin in cytoplasmic vesicles." Lim D.-S., Kirsch D.G., Canman C.E., Ahn J.-H., Ziv Y., Newman L.S., Darnell R.B., Shiloh Y., Kastan M.B. Proc. Natl. Acad. Sci. U.S.A. 95:10146-10151(1998) [PubMed: 9707615] [Abstract] Cited for: INTERACTION WITH AP2B1 AND AP3B2. |
| [5] | "ATM phosphorylates histone H2AX in response to DNA double-strand breaks." Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J. J. Biol. Chem. 276:42462-42467(2001) [PubMed: 11571274] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF H2AFX. |
| [6] | "Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo." Daniel J.A., Pellegrini M., Lee J.H., Paull T.T., Feigenbaum L., Nussenzweig A. J. Cell Biol. 183:777-783(2008) [PubMed: 19047460] [Abstract] Cited for: AUTOPHOSPHORYLATION AT SER-367; SER-1899 AND SER-1987, FUNCTION, MUTAGENESIS OF SER-367; SER-1899 AND SER-1987. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U43678 mRNA. Translation: AAC52673.1. |
| IPI | IPI00124810. |
| RefSeq | NP_031525.2. |
| UniGene | Mm.5088 |
3D structure databases | |
| SMR | Q62388. Positions 2706-2972, 3035-3065. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q62388. 2 interactions. |
| STRING | Q62388. |
PTM databases | |
| PhosphoSite | Q62388. |
Proteomic databases | |
| PRIDE | Q62388. |
Genome annotation databases | |
| Ensembl | ENSMUST00000037440; ENSMUSP00000045039; ENSMUSG00000034218; Mus musculus. [Genome view] ENSMUST00000118282; ENSMUSP00000113388; ENSMUSG00000034218; Mus musculus. [Genome view] |
| GeneID | 11920. |
| KEGG | mmu:11920. |
| UCSC | uc009pmd.1. mouse. |
Organism-specific databases | |
| CTD | 11920. |
| MGI | MGI:107202. Atm. |
Phylogenomic databases | |
| HOGENOM | HBG402889. |
| HOVERGEN | Q62388. |
| InParanoid | Q62388. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 244. |
Gene expression databases | |
| ArrayExpress | Q62388. |
| Bgee | Q62388. |
| CleanEx | MM_ATM. |
| Genevestigator | Q62388. |
| GermOnline | ENSMUSG00000034218. Mus musculus. |
Family and domain databases | |
| InterPro | IPR016024. ARM-type_fold. IPR015519. Ataxia_Telang_Mut. IPR003152. FATC. IPR011009. Kinase-like_dom. IPR000403. PI3/4_kinase_cat. IPR018936. PI3/4_kinase_CS. IPR003151. PIK-rel_kinase_FAT. IPR014009. PIK_FAT. [Graphical view] |
| PANTHER | PTHR11139:SF3. Ataxia_Telang_Mut. 1 hit. |
| Pfam | PF02259. FAT. 1 hit. PF02260. FATC. 1 hit. PF00454. PI3_PI4_kinase. 1 hit. [Graphical view] |
| SMART | SM00146. PI3Kc. 1 hit. [Graphical view] |
| PROSITE | PS51189. FAT. 1 hit. PS51190. FATC. 1 hit. PS00915. PI3_4_KINASE_1. 1 hit. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 279985. |
| SOURCE | Search... |
Entry information
| Entry name | ATM_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q62388 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


