1wfc - Revision history

OCA at 08:47, 14 February 2024

OCA — Wed, 14 Feb 2024 08:47:45 GMT

←Older revision		Revision as of 08:47, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1wfc' size='340' side='right'caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='1wfc' size='340' side='right'caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1wfc]] is a 1 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WFC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1wfc]] is a 1 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
-	</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=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [https://pdbe.org/1wfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [https://www.ebi.ac.uk/pdbsum/1wfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wfc ProSAT]</span></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]] 2.3Å</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=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [https://pdbe.org/1wfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [https://www.ebi.ac.uk/pdbsum/1wfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wfc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MK14_HUMAN MK14_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.<ref>PMID:9687510</ref> <ref>PMID:9430721</ref> <ref>PMID:9792677</ref> <ref>PMID:9858528</ref> <ref>PMID:10330143</ref> <ref>PMID:10943842</ref> <ref>PMID:10838079</ref> <ref>PMID:10747897</ref> <ref>PMID:11154262</ref> <ref>PMID:11333986</ref> <ref>PMID:15905572</ref> <ref>PMID:16932740</ref> <ref>PMID:17003045</ref> <ref>PMID:17724032</ref> <ref>PMID:19893488</ref> <ref>PMID:20932473</ref> <ref>PMID:20188673</ref>	+	[https://www.uniprot.org/uniprot/MK14_HUMAN MK14_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.<ref>PMID:9687510</ref> <ref>PMID:9430721</ref> <ref>PMID:9792677</ref> <ref>PMID:9858528</ref> <ref>PMID:10330143</ref> <ref>PMID:10943842</ref> <ref>PMID:10838079</ref> <ref>PMID:10747897</ref> <ref>PMID:11154262</ref> <ref>PMID:11333986</ref> <ref>PMID:15905572</ref> <ref>PMID:16932740</ref> <ref>PMID:17003045</ref> <ref>PMID:17724032</ref> <ref>PMID:19893488</ref> <ref>PMID:20932473</ref> <ref>PMID:20188673</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 18:		Line 19:
	</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=1wfc ConSurf].		</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=1wfc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	p38 mitogen-activated protein kinase is activated by environmental stress and cytokines and plays a role in transcriptional regulation and inflammatory responses. The crystal structure of the apo, unphosphorylated form of p38 kinase has been solved at 2.3 A resolution. The fold and topology of p38 is similar to ERK2 (Zhang, F., Strand, A., Robbins, D., Cobb, M. H., and Goldsmith, E. J. (1994) Nature 367, 704-711). The relative orientation of the two domains of p38 kinase is different from that observed in the active form of cAMP-dependent protein kinase. The twist results in a misalignment of the active site of p38, suggesting that the orientation of the domains would have to change before catalysis could proceed. The residues that are phosphorylated upon activation of p38 are located on a surface loop that occupies the peptide binding channel. Occlusion of the active site by the loop, and misalignment of catalytic residues, may account for the low enzymatic activity of unphosphorylated p38 kinase.
-
-	Crystal structure of p38 mitogen-activated protein kinase.,Wilson KP, Fitzgibbon MJ, Caron PR, Griffith JP, Chen W, McCaffrey PG, Chambers SP, Su MS J Biol Chem. 1996 Nov 1;271(44):27696-700. PMID:8910361<ref>PMID:8910361</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1wfc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Caron~~, P R~~]]	+	[[Category: Caron PR]]
-	[[Category: Chambers~~, S P~~]]	+	[[Category: Chambers SP]]
-	[[Category: Chen, W]]	+	[[Category: Chen W]]
-	[[Category: Fitzgibbon~~, M J~~]]	+	[[Category: Fitzgibbon MJ]]
-	[[Category: Griffith~~, J P~~]]	+	[[Category: Griffith JP]]
-	[[Category: Mccaffrey~~, P G~~]]	+	[[Category: Mccaffrey PG]]
-	[[Category: Su~~, M S.~~S]]	+	[[Category: Su MS-S]]
-	[[Category: Wilson~~, K P]]~~	+	[[Category: Wilson KP]]
-	~~[[Category: P38 map kinase]]~~	+
-	~~[[Category: Serine/threonine protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 16:19, 27 October 2021

OCA — Wed, 27 Oct 2021 16:19:41 GMT

←Older revision		Revision as of 16:19, 27 October 2021
Line 3:		Line 3:
	<StructureSection load='1wfc' size='340' side='right'caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='1wfc' size='340' side='right'caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WFC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1WFC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1wfc]] is a 1 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [~~http~~://pdbe.org/1wfc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1wfc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1wfc ProSAT]</span></td></tr>	+	</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=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [https://pdbe.org/1wfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [https://www.ebi.ac.uk/pdbsum/1wfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wfc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/MK14_HUMAN MK14_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.<ref>PMID:9687510</ref> <ref>PMID:9430721</ref> <ref>PMID:9792677</ref> <ref>PMID:9858528</ref> <ref>PMID:10330143</ref> <ref>PMID:10943842</ref> <ref>PMID:10838079</ref> <ref>PMID:10747897</ref> <ref>PMID:11154262</ref> <ref>PMID:11333986</ref> <ref>PMID:15905572</ref> <ref>PMID:16932740</ref> <ref>PMID:17003045</ref> <ref>PMID:17724032</ref> <ref>PMID:19893488</ref> <ref>PMID:20932473</ref> <ref>PMID:20188673</ref>	+	[[https://www.uniprot.org/uniprot/MK14_HUMAN MK14_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.<ref>PMID:9687510</ref> <ref>PMID:9430721</ref> <ref>PMID:9792677</ref> <ref>PMID:9858528</ref> <ref>PMID:10330143</ref> <ref>PMID:10943842</ref> <ref>PMID:10838079</ref> <ref>PMID:10747897</ref> <ref>PMID:11154262</ref> <ref>PMID:11333986</ref> <ref>PMID:15905572</ref> <ref>PMID:16932740</ref> <ref>PMID:17003045</ref> <ref>PMID:17724032</ref> <ref>PMID:19893488</ref> <ref>PMID:20932473</ref> <ref>PMID:20188673</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 17:14, 22 January 2020

OCA — Wed, 22 Jan 2020 17:14:49 GMT

←Older revision		Revision as of 17:14, 22 January 2020
Line 1:		Line 1:

	==STRUCTURE OF APO, UNPHOSPHORYLATED, P38 MITOGEN ACTIVATED PROTEIN KINASE P38 (P38 MAP KINASE) THE MAMMALIAN HOMOLOGUE OF THE YEAST HOG1 PROTEIN==		==STRUCTURE OF APO, UNPHOSPHORYLATED, P38 MITOGEN ACTIVATED PROTEIN KINASE P38 (P38 MAP KINASE) THE MAMMALIAN HOMOLOGUE OF THE YEAST HOG1 PROTEIN==
-	<StructureSection load='1wfc' size='340' side='right' caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='1wfc' size='340' side='right'caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>		<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
Line 29:		Line 29:

	==See Also==		==See Also==
-	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]	+	*[[Mitogen-activated protein kinase 3D structures\|Mitogen-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Caron, P R]]		[[Category: Caron, P R]]
	[[Category: Chambers, S P]]		[[Category: Chambers, S P]]

OCA at 16:01, 11 April 2018

OCA — Wed, 11 Apr 2018 16:01:27 GMT

←Older revision		Revision as of 16:01, 11 April 2018
Line 1:		Line 1:
		+
	==STRUCTURE OF APO, UNPHOSPHORYLATED, P38 MITOGEN ACTIVATED PROTEIN KINASE P38 (P38 MAP KINASE) THE MAMMALIAN HOMOLOGUE OF THE YEAST HOG1 PROTEIN==		==STRUCTURE OF APO, UNPHOSPHORYLATED, P38 MITOGEN ACTIVATED PROTEIN KINASE P38 (P38 MAP KINASE) THE MAMMALIAN HOMOLOGUE OF THE YEAST HOG1 PROTEIN==
	<StructureSection load='1wfc' size='340' side='right' caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='1wfc' size='340' side='right' caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>		<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://pdbe.org/1wfc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://pdbe.org/1wfc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wfc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 11:		Line 12:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wf/1wfc_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wf/1wfc_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 39:		Line 40:
	[[Category: Fitzgibbon, M J]]		[[Category: Fitzgibbon, M J]]
	[[Category: Griffith, J P]]		[[Category: Griffith, J P]]
-	[[Category: Mccaffrey, P. G]]	+	[[Category: Mccaffrey, P G]]
	[[Category: Su, M S.S]]		[[Category: Su, M S.S]]
	[[Category: Wilson, K P]]		[[Category: Wilson, K P]]

OCA at 12:38, 9 February 2016

OCA — Tue, 09 Feb 2016 12:38:48 GMT

←Older revision		Revision as of 12:38, 9 February 2016
Line 15:		Line 15:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</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=1wfc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 22:19, 10 September 2015

OCA — Thu, 10 Sep 2015 22:19:51 GMT

←Older revision		Revision as of 22:19, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1wfc' size='340' side='right' caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='1wfc' size='340' side='right' caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://pdbe.org/1wfc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 25:		Line 25:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1wfc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 32:		Line 33:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Caron, P R]]		[[Category: Caron, P R]]
	[[Category: Chambers, S P]]		[[Category: Chambers, S P]]

OCA at 06:52, 25 December 2014

OCA — Thu, 25 Dec 2014 06:52:20 GMT

←Older revision		Revision as of 06:52, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>		<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MK14_HUMAN MK14_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.<ref>PMID:9687510</ref> <ref>PMID:9430721</ref> <ref>PMID:9792677</ref> <ref>PMID:9858528</ref> <ref>PMID:10330143</ref> <ref>PMID:10943842</ref> <ref>PMID:10838079</ref> <ref>PMID:10747897</ref> <ref>PMID:11154262</ref> <ref>PMID:11333986</ref> <ref>PMID:15905572</ref> <ref>PMID:16932740</ref> <ref>PMID:17003045</ref> <ref>PMID:17724032</ref> <ref>PMID:19893488</ref> <ref>PMID:20932473</ref> <ref>PMID:20188673</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 31:		Line 33:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Caron, P R.]]	+	[[Category: Caron, P R]]
-	[[Category: Chambers, S P.]]	+	[[Category: Chambers, S P]]
-	[[Category: Chen, W.]]	+	[[Category: Chen, W]]
-	[[Category: Fitzgibbon, M J.]]	+	[[Category: Fitzgibbon, M J]]
-	[[Category: Griffith, J P.]]	+	[[Category: Griffith, J P]]
-	[[Category: Mccaffrey, P. G.]]	+	[[Category: Mccaffrey, P. G]]
-	[[Category: Su, M S.S.]]	+	[[Category: Su, M S.S]]
-	[[Category: Wilson, K P.]]	+	[[Category: Wilson, K P]]
	[[Category: P38 map kinase]]		[[Category: P38 map kinase]]
	[[Category: Serine/threonine protein kinase]]		[[Category: Serine/threonine protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:17, 28 September 2014

OCA — Sun, 28 Sep 2014 19:17:53 GMT

←Older revision		Revision as of 19:17, 28 September 2014
Line 1:		Line 1:
-	[[~~Image~~:1wfc.~~png\|left~~\|200px]]	+	==STRUCTURE OF APO, UNPHOSPHORYLATED, P38 MITOGEN ACTIVATED PROTEIN KINASE P38 (P38 MAP KINASE) THE MAMMALIAN HOMOLOGUE OF THE YEAST HOG1 PROTEIN==
		+	<StructureSection load='1wfc' size='340' side='right' caption='[[1wfc]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1wfc]] is a 1 chain structure with 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=1WFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WFC FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wfc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wfc RCSB], [http://www.ebi.ac.uk/pdbsum/1wfc PDBsum]</span></td></tr>
		+	<table>
		+	== 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/wf/1wfc_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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	p38 mitogen-activated protein kinase is activated by environmental stress and cytokines and plays a role in transcriptional regulation and inflammatory responses. The crystal structure of the apo, unphosphorylated form of p38 kinase has been solved at 2.3 A resolution. The fold and topology of p38 is similar to ERK2 (Zhang, F., Strand, A., Robbins, D., Cobb, M. H., and Goldsmith, E. J. (1994) Nature 367, 704-711). The relative orientation of the two domains of p38 kinase is different from that observed in the active form of cAMP-dependent protein kinase. The twist results in a misalignment of the active site of p38, suggesting that the orientation of the domains would have to change before catalysis could proceed. The residues that are phosphorylated upon activation of p38 are located on a surface loop that occupies the peptide binding channel. Occlusion of the active site by the loop, and misalignment of catalytic residues, may account for the low enzymatic activity of unphosphorylated p38 kinase.

-	~~{{STRUCTURE_1wfc\| PDB=1wfc \| SCENE= }}~~	+	Crystal structure of p38 mitogen-activated protein kinase.,Wilson KP, Fitzgibbon MJ, Caron PR, Griffith JP, Chen W, McCaffrey PG, Chambers SP, Su MS J Biol Chem. 1996 Nov 1;271(44):27696-700. PMID:8910361<ref>PMID:8910361</ref>

-	~~===STRUCTURE OF APO~~, ~~UNPHOSPHORYLATED, P38 MITOGEN ACTIVATED PROTEIN KINASE P38 (P38 MAP KINASE) THE MAMMALIAN HOMOLOGUE OF THE YEAST HOG1 PROTEIN===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_8910361}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1wfc]] is~~ a ~~1 chain structure with 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=1WFC OCA].~~	+

	==See Also==		==See Also==
	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]		*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:008910361<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Caron, P R.]]		[[Category: Caron, P R.]]

OCA at 13:51, 20 October 2012

OCA — Sat, 20 Oct 2012 13:51:56 GMT

←Older revision		Revision as of 13:51, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[1wfc]] is a 1 chain structure ~~of [[Mitogen-activated protein kinase]]~~ with 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=1WFC OCA].	+	[[1wfc]] is a 1 chain structure with 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=1WFC OCA].

	==See Also==		==See Also==

OCA: Protected "1wfc" [edit=sysop:move=sysop]

OCA — Thu, 26 Jul 2012 13:21:30 GMT

Protected "1wfc" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:21, 26 July 2012