InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Atm

Summary

InnateDB Protein

IDBP-401090.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Atm

Protein Name

ataxia telangiectasia mutated homolog (human)

Synonyms

AI256621; C030026E19Rik;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000113388

InnateDB Gene

IDBG-165511 (Atm)

Protein Structure

UniProt Annotation

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 plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, 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. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. {ECO:0000269PubMed:11571274, ECO:0000269PubMed:19047460, ECO:0000269PubMed:19448632}.

Subcellular Localization

Nucleus {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Note=Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin (By similarity). {ECO:0000250}.

Disease Associations

Note=Atm-deficient mice show a phenotype similar to human ataxia telangiectasia (AT) and consistently develop immature T- cells malignancies.

Tissue Specificity

Expressed in brain, skeletal muscle, testis, followed by spleen, lung, kidney, heart, liver and thymus. Ubiquitously expressed in embryonal tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 120 interaction(s) predicted by orthology.

Experimentally validated
Total	19 [view]
Protein-Protein	18 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	120 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004677	DNA-dependent protein kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016303	1-phosphatidylinositol-3-kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0032403	protein complex binding
GO:0035174	histone serine kinase activity
GO:0046983	protein dimerization activity
GO:0047485	protein N-terminus binding

Biological Process

GO:0000077	DNA damage checkpoint
GO:0000723	telomere maintenance
GO:0001666	response to hypoxia
GO:0001756	somitogenesis
GO:0002331	pre-B cell allelic exclusion
GO:0006281	DNA repair
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0006975	DNA damage induced protein phosphorylation
GO:0007050	cell cycle arrest
GO:0007094	mitotic spindle assembly checkpoint
GO:0007292	female gamete generation
GO:0007420	brain development
GO:0007507	heart development
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010212	response to ionizing radiation
GO:0016572	histone phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0030889	negative regulation of B cell proliferation
GO:0035404	histone-serine phosphorylation
GO:0036092	phosphatidylinositol-3-phosphate biosynthetic process
GO:0042159	lipoprotein catabolic process
GO:0043065	positive regulation of apoptotic process
GO:0043517	positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0043525	positive regulation of neuron apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0046777	protein autophosphorylation
GO:0048599	oocyte development
GO:0051402	neuron apoptotic process
GO:0051726	regulation of cell cycle
GO:0071044	histone mRNA catabolic process
GO:0071480	cellular response to gamma radiation
GO:0072434	signal transduction involved in mitotic G2 DNA damage checkpoint
GO:0090399	replicative senescence

Cellular Component

GO:0000781	chromosome, telomeric region
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005819	spindle
GO:0016023	cytoplasmic membrane-bounded vesicle

Protein Structure and Domains

PDB ID

MGI:107202

InterPro

IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003151 PIK-related kinase, FAT
IPR003152 PIK-related kinase, FATC
IPR011009 Protein kinase-like domain
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold
IPR021668 Telomere-length maintenance and DNA damage repair

PFAM

PF00454
PF02259
PF02260
PF11640

PRINTS

PIRSF

SMART

SM00146

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q62388