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2a2a

From Proteopedia

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Current revision

High-resolution crystallographic analysis of the autoinhibited conformation of a human death-associated protein kinase

Structural highlights

2a2a is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.47Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DAPK2_HUMAN Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The regulation of many protein kinases by binding to calcium/calmodulin connects two principal mechanisms in signaling processes: protein phosphorylation and responses to dose- and time-dependent calcium signals. We used the calcium/calmodulin-dependent members of the death-associated protein kinase (DAPK) family to investigate the role of a basic DAPK signature loop near the kinase active site. In DAPK2, this loop comprises a novel dimerization-regulated calcium/calmodulin-binding site, in addition to a well-established calcium/calmodulin site in the C-terminal autoregulatory domain. Unexpectedly, impairment of the basic loop interaction site completely abolishes calcium/calmodulin binding and DAPK2 activity is reduced to a residual level, indicative of coupled binding to the two sites. This contrasts with the generally accepted view that kinase calcium/calmodulin interactions are autonomous of the kinase catalytic domain. Our data establish an intricate model of multi-step kinase activation and expand our understanding of how calcium binding connects with other mechanisms involved in kinase activity regulation.

Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites.,Simon B, Huart AS, Temmerman K, Vahokoski J, Mertens HD, Komadina D, Hoffmann JE, Yumerefendi H, Svergun DI, Kursula P, Schultz C, McCarthy AA, Hart DJ, Wilmanns M Structure. 2016 Apr 20. pii: S0969-2126(16)30030-2. doi:, 10.1016/j.str.2016.03.020. PMID:27133022^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kawai T, Nomura F, Hoshino K, Copeland NG, Gilbert DJ, Jenkins NA, Akira S. Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity. Oncogene. 1999 Jun 10;18(23):3471-80. PMID:10376525 doi:http://dx.doi.org/10.1038/sj.onc.1202701
↑ Inbal B, Shani G, Cohen O, Kissil JL, Kimchi A. Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Mol Cell Biol. 2000 Feb;20(3):1044-54. PMID:10629061
↑ Shoval Y, Berissi H, Kimchi A, Pietrokovski S. New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS One. 2011 Mar 8;6(2):e17344. doi: 10.1371/journal.pone.0017344. PMID:21408167 doi:10.1371/journal.pone.0017344
↑ Shani G, Henis-Korenblit S, Jona G, Gileadi O, Eisenstein M, Ziv T, Admon A, Kimchi A. Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. EMBO J. 2001 Mar 1;20(5):1099-113. PMID:11230133 doi:http://dx.doi.org/10.1093/emboj/20.5.1099
↑ Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol. 2002 Apr 29;157(3):455-68. Epub 2002 Apr 29. PMID:11980920 doi:10.1083/jcb.200109094
↑ Rizzi M, Tschan MP, Britschgi C, Britschgi A, Hugli B, Grob TJ, Leupin N, Mueller BU, Simon HU, Ziemiecki A, Torbett BE, Fey MF, Tobler A. The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells. J Leukoc Biol. 2007 Jun;81(6):1599-608. Epub 2007 Mar 8. PMID:17347302 doi:http://dx.doi.org/10.1189/jlb.0606400
↑ Li H, Ray G, Yoo BH, Erdogan M, Rosen KV. Down-regulation of death-associated protein kinase-2 is required for beta-catenin-induced anoikis resistance of malignant epithelial cells. J Biol Chem. 2009 Jan 23;284(4):2012-22. doi: 10.1074/jbc.M805612200. Epub 2008, Oct 27. PMID:18957423 doi:10.1074/jbc.M805612200
↑ Kawai T, Nomura F, Hoshino K, Copeland NG, Gilbert DJ, Jenkins NA, Akira S. Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity. Oncogene. 1999 Jun 10;18(23):3471-80. PMID:10376525 doi:http://dx.doi.org/10.1038/sj.onc.1202701
↑ Inbal B, Shani G, Cohen O, Kissil JL, Kimchi A. Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Mol Cell Biol. 2000 Feb;20(3):1044-54. PMID:10629061
↑ Shoval Y, Berissi H, Kimchi A, Pietrokovski S. New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS One. 2011 Mar 8;6(2):e17344. doi: 10.1371/journal.pone.0017344. PMID:21408167 doi:10.1371/journal.pone.0017344
↑ Shani G, Henis-Korenblit S, Jona G, Gileadi O, Eisenstein M, Ziv T, Admon A, Kimchi A. Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. EMBO J. 2001 Mar 1;20(5):1099-113. PMID:11230133 doi:http://dx.doi.org/10.1093/emboj/20.5.1099
↑ Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol. 2002 Apr 29;157(3):455-68. Epub 2002 Apr 29. PMID:11980920 doi:10.1083/jcb.200109094
↑ Rizzi M, Tschan MP, Britschgi C, Britschgi A, Hugli B, Grob TJ, Leupin N, Mueller BU, Simon HU, Ziemiecki A, Torbett BE, Fey MF, Tobler A. The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells. J Leukoc Biol. 2007 Jun;81(6):1599-608. Epub 2007 Mar 8. PMID:17347302 doi:http://dx.doi.org/10.1189/jlb.0606400
↑ Li H, Ray G, Yoo BH, Erdogan M, Rosen KV. Down-regulation of death-associated protein kinase-2 is required for beta-catenin-induced anoikis resistance of malignant epithelial cells. J Biol Chem. 2009 Jan 23;284(4):2012-22. doi: 10.1074/jbc.M805612200. Epub 2008, Oct 27. PMID:18957423 doi:10.1074/jbc.M805612200
↑ Simon B, Huart AS, Temmerman K, Vahokoski J, Mertens HD, Komadina D, Hoffmann JE, Yumerefendi H, Svergun DI, Kursula P, Schultz C, McCarthy AA, Hart DJ, Wilmanns M. Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites. Structure. 2016 Apr 20. pii: S0969-2126(16)30030-2. doi:, 10.1016/j.str.2016.03.020. PMID:27133022 doi:http://dx.doi.org/10.1016/j.str.2016.03.020

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2a2a"

Categories: Homo sapiens | Large Structures | Kursula P | Wilmanns M

@@ Line 3: / Line 3: @@
 <StructureSection load='2a2a' size='340' side='right'caption='[[2a2a]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2a2a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A2A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2a2a]] is a 4 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=2A2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A2A FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.47&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2a27|2a27]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></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=2a2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a2a OCA], [https://pdbe.org/2a2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a2a RCSB], [https://www.ebi.ac.uk/pdbsum/2a2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a2a ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DAPK2_HUMAN DAPK2_HUMAN]] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref>   Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref>
+[https://www.uniprot.org/uniprot/DAPK2_HUMAN DAPK2_HUMAN] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref>   Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Transferase]]
+[[Category: Kursula P]]
-[[Category: Kursula, P]]
+[[Category: Wilmanns M]]
-[[Category: Wilmanns, M]]
-[[Category: Autoinhibition]]
-[[Category: Protein kinase]]

2a2a

From Proteopedia

Current revision

High-resolution crystallographic analysis of the autoinhibited conformation of a human death-associated protein kinase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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