View source for 8oxq


==ATM(Q2971A) dimeric C-terminal region in complex with Mg AMP-PNP==
<StructureSection load='8oxq' size='340' side='right'caption='[[8oxq]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8oxq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OXQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8oxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oxq OCA], [https://pdbe.org/8oxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oxq RCSB], [https://www.ebi.ac.uk/pdbsum/8oxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oxq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ATM_HUMAN ATM_HUMAN] Mantle cell lymphoma;B-cell chronic lymphocytic leukemia;Combined cervical dystonia;Ataxia-telangiectasia;Ataxia-telangiectasia variant. The disease is caused by mutations affecting the gene represented in this entry.  Defects in ATM contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients.<ref>PMID:9288106</ref> <ref>PMID:9334731</ref> <ref>PMID:9463314</ref> <ref>PMID:9488043</ref> <ref>PMID:9573030</ref>   Defects in ATM contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL).<ref>PMID:10397742</ref> <ref>PMID:10706620</ref> <ref>PMID:9288106</ref>   Defects in ATM contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B-lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.<ref>PMID:10023947</ref> <ref>PMID:10397742</ref> <ref>PMID:9892178</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ATM_HUMAN ATM_HUMAN] 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. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. 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.<ref>PMID:10973490</ref> <ref>PMID:12556884</ref> <ref>PMID:14871926</ref> <ref>PMID:15916964</ref> <ref>PMID:16086026</ref> <ref>PMID:16858402</ref> <ref>PMID:17923702</ref> <ref>PMID:19965871</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Howes AC]]
[[Category: Perisic O]]
[[Category: Williams RL]]