2clq: Difference between revisions

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[[Image:2clq.png|left|200px]]


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==Structure of mitogen-activated protein kinase kinase kinase 5==
The line below this paragraph, containing "STRUCTURE_2clq", creates the "Structure Box" on the page.
<StructureSection load='2clq' size='340' side='right'caption='[[2clq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2clq]] 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=2CLQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CLQ FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
{{STRUCTURE_2clq| PDB=2clq |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2clq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2clq OCA], [https://pdbe.org/2clq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2clq RCSB], [https://www.ebi.ac.uk/pdbsum/2clq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2clq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/M3K5_HUMAN M3K5_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).<ref>PMID:8940179</ref> <ref>PMID:8974401</ref> <ref>PMID:9564042</ref> <ref>PMID:9774977</ref> <ref>PMID:10411906</ref> <ref>PMID:10849426</ref> <ref>PMID:10688666</ref> <ref>PMID:11689443</ref> <ref>PMID:11029458</ref> <ref>PMID:11154276</ref> <ref>PMID:14749717</ref> <ref>PMID:11920685</ref> <ref>PMID:12697749</ref> <ref>PMID:15023544</ref> <ref>PMID:14688258</ref> <ref>PMID:16129676</ref> <ref>PMID:17220297</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cl/2clq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2clq ConSurf].
<div style="clear:both"></div>


===STRUCTURE OF MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 5===
==See Also==
 
*[[Mitogen-activated protein kinase kinase kinase|Mitogen-activated protein kinase kinase kinase]]
 
== References ==
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{{ABSTRACT_PUBMED_17937911}}
 
==About this Structure==
2CLQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CLQ OCA].
 
==Reference==
Structural and functional characterization of the human protein kinase ASK1., Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Muller S, Sobott F, Parker SA, Zhang H, Min W, Turk BE, Knapp S, Structure. 2007 Oct;15(10):1215-26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17937911 17937911]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Mitogen-activated protein kinase kinase kinase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Arrowsmith C]]
[[Category: Arrowsmith, C.]]
[[Category: Bunkoczi G]]
[[Category: Bunkoczi, G.]]
[[Category: Edwards A]]
[[Category: Delft, F Von.]]
[[Category: Fedorov O]]
[[Category: Edwards, A.]]
[[Category: Gileadi O]]
[[Category: Fedorov, O.]]
[[Category: Knapp S]]
[[Category: Gileadi, O.]]
[[Category: Pike A]]
[[Category: Knapp, S.]]
[[Category: Salah E]]
[[Category: Pike, A.]]
[[Category: Sundstrom M]]
[[Category: Salah, E.]]
[[Category: Weigelt J]]
[[Category: Sundstrom, M.]]
[[Category: Von Delft F]]
[[Category: Weigelt, J.]]
[[Category: Apoptosis]]
[[Category: Atp-binding]]
[[Category: Kinase]]
[[Category: Magnesium]]
[[Category: Map kinase]]
[[Category: Metal-binding]]
[[Category: Nucleotide-binding]]
[[Category: Phosphorylation]]
[[Category: Protein kinase]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:19:51 2008''

Latest revision as of 09:39, 1 May 2024

Structure of mitogen-activated protein kinase kinase kinase 5Structure of mitogen-activated protein kinase kinase kinase 5

Structural highlights

2clq is a 2 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 2.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

M3K5_HUMAN Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]

Evolutionary Conservation

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

See Also

References

  1. ↑ Wang XS, Diener K, Jannuzzi D, Trollinger D, Tan TH, Lichenstein H, Zukowski M, Yao Z. Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase. J Biol Chem. 1996 Dec 6;271(49):31607-11. PMID:8940179
  2. ↑ Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K, Gotoh Y. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997 Jan 3;275(5296):90-4. PMID:8974401
  3. ↑ Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 1998 May 1;17(9):2596-606. PMID:9564042 doi:10.1093/emboj/17.9.2596
  4. ↑ Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H. ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell. 1998 Sep;2(3):389-95. PMID:9774977
  5. ↑ Zhang L, Chen J, Fu H. Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8511-5. PMID:10411906
  6. ↑ Hatai T, Matsuzawa A, Inoshita S, Mochida Y, Kuroda T, Sakamaki K, Kuida K, Yonehara S, Ichijo H, Takeda K. Execution of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis by the mitochondria-dependent caspase activation. J Biol Chem. 2000 Aug 25;275(34):26576-81. PMID:10849426 doi:10.1074/jbc.M003412200
  7. ↑ Liu H, Nishitoh H, Ichijo H, Kyriakis JM. Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor-associated factor 2 requires prior dissociation of the ASK1 inhibitor thioredoxin. Mol Cell Biol. 2000 Mar;20(6):2198-208. PMID:10688666
  8. ↑ Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H. Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress. EMBO J. 2001 Nov 1;20(21):6028-36. PMID:11689443 doi:10.1093/emboj/20.21.6028
  9. ↑ Sayama K, Hanakawa Y, Shirakata Y, Yamasaki K, Sawada Y, Sun L, Yamanishi K, Ichijo H, Hashimoto K. Apoptosis signal-regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation. J Biol Chem. 2001 Jan 12;276(2):999-1004. PMID:11029458 doi:10.1074/jbc.M003425200
  10. ↑ Kim AH, Khursigara G, Sun X, Franke TF, Chao MV. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol. 2001 Feb;21(3):893-901. PMID:11154276 doi:10.1128/MCB.21.3.893-901.2001
  11. ↑ Takeda K, Matsuzawa A, Nishitoh H, Tobiume K, Kishida S, Ninomiya-Tsuji J, Matsumoto K, Ichijo H. Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation. EMBO Rep. 2004 Feb;5(2):161-6. Epub 2004 Jan 16. PMID:14749717 doi:10.1038/sj.embor.7400072
  12. ↑ Tobiume K, Saitoh M, Ichijo H. Activation of apoptosis signal-regulating kinase 1 by the stress-induced activating phosphorylation of pre-formed oligomer. J Cell Physiol. 2002 Apr;191(1):95-104. PMID:11920685 doi:10.1002/jcp.10080
  13. ↑ Yuan ZQ, Feldman RI, Sussman GE, Coppola D, Nicosia SV, Cheng JQ. AKT2 inhibition of cisplatin-induced JNK/p38 and Bax activation by phosphorylation of ASK1: implication of AKT2 in chemoresistance. J Biol Chem. 2003 Jun 27;278(26):23432-40. Epub 2003 Apr 15. PMID:12697749 doi:10.1074/jbc.M302674200
  14. ↑ Subramanian RR, Zhang H, Wang H, Ichijo H, Miyashita T, Fu H. Interaction of apoptosis signal-regulating kinase 1 with isoforms of 14-3-3 proteins. Exp Cell Res. 2004 Apr 1;294(2):581-91. PMID:15023544 doi:10.1016/j.yexcr.2003.12.009
  15. ↑ Goldman EH, Chen L, Fu H. Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. J Biol Chem. 2004 Mar 12;279(11):10442-9. Epub 2003 Dec 19. PMID:14688258 doi:10.1074/jbc.M311129200
  16. ↑ Noguchi T, Takeda K, Matsuzawa A, Saegusa K, Nakano H, Gohda J, Inoue J, Ichijo H. Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death. J Biol Chem. 2005 Nov 4;280(44):37033-40. Epub 2005 Aug 29. PMID:16129676 doi:10.1074/jbc.M506771200
  17. ↑ Zhao Y, Conze DB, Hanover JA, Ashwell JD. Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling. J Biol Chem. 2007 Mar 16;282(11):7777-82. Epub 2007 Jan 12. PMID:17220297 doi:10.1074/jbc.M609146200

2clq, resolution 2.30Å

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