3blh - Revision history

OCA at 08:49, 30 October 2024

2024-10-30T08:49:30Z

← Older revision		Revision as of 08:49, 30 October 2024
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	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3blh_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3blh_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>

OCA at 14:47, 1 November 2023

2023-11-01T14:47:55Z

← Older revision		Revision as of 14:47, 1 November 2023
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	<StructureSection load='3blh' size='340' side='right'caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='3blh' size='340' side='right'caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BLH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3blh]] 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BLH FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=TRS:2-AMINO~~-2~~-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 2.48Å</td></tr>
	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene><~~/td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat"><div style='overflow: auto; max~~-~~height: 3em;'>[[3blq\|3blq]]~~, ~~[[3blr\|3blr]]</div></td></tr>~~
	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</~~b></td><td class="sblockDat"~~>CDK9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNT1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [https://pdbe.org/3blh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [https://www.ebi.ac.uk/pdbsum/3blh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3blh ProSAT]</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [https://pdbe.org/3blh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [https://www.ebi.ac.uk/pdbsum/3blh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3blh ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.		[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</ref> [[https://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN]] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.		[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Baumli, S]]		[[Category: Baumli S]]
	[[Category: Johnson~~, L N~~]]		[[Category: Johnson LN]]
	[[Category: Lolli, G]]		[[Category: Lolli G]]
	[[Category: Lowe~~, E D]]~~		[[Category: Lowe ED]]
	~~[[Category: Acetylation]]~~
	~~[[Category: Alternative splicing]]~~
	~~[[Category: Atp-binding]]~~
	~~[[Category: Cell cycle]]~~
	~~[[Category: Cell division]]~~
	~~[[Category: Coiled coil]]~~
	~~[[Category: Host-virus interaction]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Nucleotide-binding]]~~
	~~[[Category: Nucleus]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Phosphorylated]]~~
	~~[[Category: Polymorphism]]~~
	~~[[Category: Serine/threonine-protein kinase]]~~
	~~[[Category: Transcription]]~~
	~~[[Category: Transcription regulation]]~~
	~~[[Category: Transcriptional cdk-cyclin complex]]~~
	~~[[Category: Transferase~~]]

OCA at 07:27, 10 November 2021

2021-11-10T07:27:18Z

← Older revision		Revision as of 07:27, 10 November 2021
Line 1:		Line 1:

	==Crystal Structure of Human CDK9/cyclinT1==		==Crystal Structure of Human CDK9/cyclinT1==
	<StructureSection load='3blh' size='340' side='right' caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='3blh' size='340' side='right'caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3BLH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BLH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3blq\|3blq]], [[3blr\|3blr]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNT1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNT1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [~~http~~://pdbe.org/3blh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3blh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3blh ProSAT]</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [https://pdbe.org/3blh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [https://www.ebi.ac.uk/pdbsum/3blh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3blh ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.		[[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</ref> [[~~http~~://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN]] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.		[[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</ref> [[https://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN]] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 36:
	==See Also==		==See Also==
	*[[Cyclin\|Cyclin]]		*[[Cyclin\|Cyclin]]
	*[[Cyclin-dependent kinase\|Cyclin-dependent kinase]]		*[[Cyclin 3D structures\|Cyclin 3D structures]]
			*[[Cyclin-dependent kinase 3D structures\|Cyclin-dependent kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 42:		Line 43:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Baumli, S]]		[[Category: Baumli, S]]
	[[Category: Johnson, L N]]		[[Category: Johnson, L N]]

OCA at 08:22, 31 October 2018

2018-10-31T08:22:44Z

← Older revision		Revision as of 08:22, 31 October 2018
Line 1:		Line 1:

	==Crystal Structure of Human CDK9/cyclinT1==		==Crystal Structure of Human CDK9/cyclinT1==
	<StructureSection load='3blh' size='340' side='right' caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='3blh' size='340' side='right' caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>
Line 7:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://pdbe.org/3blh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum]</span></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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://pdbe.org/3blh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3blh ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3blh_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3blh_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 45:		Line 46:
	[[Category: Lolli, G]]		[[Category: Lolli, G]]
	[[Category: Lowe, E D]]		[[Category: Lowe, E D]]
			[[Category: Acetylation]]
			[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Cell division]]		[[Category: Cell division]]
			[[Category: Coiled coil]]
	[[Category: Host-virus interaction]]		[[Category: Host-virus interaction]]
	[[Category: Kinase]]		[[Category: Kinase]]
Line 54:		Line 58:
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	[[Category: Phosphorylated]]		[[Category: Phosphorylated]]
			[[Category: Polymorphism]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 22:35, 8 February 2016

2016-02-08T22:35:52Z

← Older revision		Revision as of 22:35, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3blh' size='340' side='right' caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='3blh' size='340' side='right' caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BLH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BLH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum]</span></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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://pdbe.org/3blh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	<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=3blh ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 31:		Line 31:
	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 3blh" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 39:		Line 40:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Baumli, S]]		[[Category: Baumli, S]]
	[[Category: Johnson, L N]]		[[Category: Johnson, L N]]

OCA at 11:50, 20 January 2015

2015-01-20T11:50:47Z

← Older revision		Revision as of 11:50, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BLH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BLH FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum]</span></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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.		[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
Line 40:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Baumli, S.]]		[[Category: Baumli, S]]
	[[Category: Johnson, L N.]]		[[Category: Johnson, L N]]
	[[Category: Lolli, G.]]		[[Category: Lolli, G]]
	[[Category: Lowe, E D.]]		[[Category: Lowe, E D]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]

OCA at 21:36, 2 October 2014

2014-10-02T21:36:00Z

← Older revision		Revision as of 21:36, 2 October 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3blh~~\| ~~PDB~~=3blh \| ~~SCENE~~= }}		==Crystal Structure of Human CDK9/cyclinT1==
	===~~Crystal Structure of Human~~ CDK9/~~cyclinT1~~===		<StructureSection load='3blh' size='340' side='right' caption='[[3blh]], [[Resolution\|resolution]] 2.48Å' scene=''>
	~~{{ABSTRACT_PUBMED_18566585}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3blh]] is a 2 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=3BLH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BLH FirstGlance]. <br>
	==Disease==		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene><br>
			<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3blq\|3blq]], [[3blr\|3blr]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CCNT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3blh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3blh RCSB], [http://www.ebi.ac.uk/pdbsum/3blh PDBsum]</span></td></tr>
			<table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.		[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
			== Function ==
			[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</ref> [[http://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN]] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.
			== 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/bl/3blh_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 ==
			The positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II. To understand the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2. There are distinct differences between CDK9/CycT1 and the cell cycle CDK CDK2/CycA manifested by a relative rotation of 26 degrees of CycT1 with respect to the CDK, showing for the first time plasticity in CDK cyclin interactions. The CDK9/CycT1 interface is relatively sparse but retains some core CDK-cyclin interactions. The CycT1 C-terminal helix shows flexibility that may be important for the interaction of this region with HIV TAT and HEXIM. Flavopiridol, an anticancer drug in phase II clinical trials, binds to the ATP site of CDK9 inducing unanticipated structural changes that bury the inhibitor. CDK9 activity and recognition of regulatory proteins are governed by autophosphorylation. We show that CDK9/CycT1 autophosphorylates on Thr186 in the activation segment and three C-terminal phosphorylation sites. Autophosphorylation on all sites occurs in cis.

	~~==Function==~~		The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation.,Baumli S, Lolli G, Lowe ED, Troiani S, Rusconi L, Bullock AN, Debreczeni JE, Knapp S, Johnson LN EMBO J. 2008 Jul 9;27(13):1907-18. Epub 2008 Jun 19. PMID:18566585<ref>PMID:18566585</ref>
	~~[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Protein kinase involved in the regulation~~ of ~~transcription. Member of the cyclin~~-~~dependent kinase pair~~ (CDK9/cyclin-T) complex~~, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation~~ by ~~phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP~~. ~~This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300~~, ~~MYOD1~~, ~~RPB1/POLR2A and AR~~, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, ~~differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification~~, ~~mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1)~~, H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, ~~by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress~~, ~~thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition~~, ~~probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6~~. ~~Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser~~-~~2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth~~. ~~DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation~~.~~<ref>PMID:9857195</ref><ref>~~PMID:~~10393184</ref>~~<ref>PMID:~~10574912~~</ref><ref>PMID:10912001</ref><ref>PMID:10757782</ref><ref>PMID:11145967</ref><ref>PMID:11112772</ref><ref>PMID:11575923</ref><ref>PMID:11884399</ref><ref>PMID:11809800</ref><ref>PMID:12037670</ref><ref>PMID:15564463</ref><ref>PMID:14701750</ref><ref>PMID:17956865</ref><ref>PMID:18362169</ref><ref>PMID:19844166</ref><ref>PMID:19575011</ref><ref>PMID:20493174</ref><ref>PMID:20930849</ref><ref>PMID:20081228</ref><ref>PMID:20980437</ref><ref>PMID:21127351</ref> [[http://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN]] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[3blh]] is~~ a ~~2 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=3BLH OCA].~~		</div>

	==See Also==		==See Also==
	*[[Cyclin\|Cyclin]]		*[[Cyclin\|Cyclin]]
	*[[Cyclin-dependent kinase\|Cyclin-dependent kinase]]		*[[Cyclin-dependent kinase\|Cyclin-dependent kinase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:018566585</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Baumli, S.]]		[[Category: Baumli, S.]]

OCA at 22:34, 24 March 2013

2013-03-24T22:34:19Z

← Older revision		Revision as of 22:34, 24 March 2013
Line 1:		Line 1:
	~~[[Image:3blh.png\|left\|200px]]~~

	{{STRUCTURE_3blh\| PDB=3blh \| SCENE= }}		{{STRUCTURE_3blh\| PDB=3blh \| SCENE= }}
			===Crystal Structure of Human CDK9/cyclinT1===
			{{ABSTRACT_PUBMED_18566585}}

	===~~Crystal Structure~~ of ~~Human~~ CDK9~~/cyclinT1===~~		==Disease==
			[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.

	~~{{ABSTRACT_PUBMED_18566585}}~~		==Function==
			[[http://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN]] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref><ref>PMID:10393184</ref><ref>PMID:10574912</ref><ref>PMID:10912001</ref><ref>PMID:10757782</ref><ref>PMID:11145967</ref><ref>PMID:11112772</ref><ref>PMID:11575923</ref><ref>PMID:11884399</ref><ref>PMID:11809800</ref><ref>PMID:12037670</ref><ref>PMID:15564463</ref><ref>PMID:14701750</ref><ref>PMID:17956865</ref><ref>PMID:18362169</ref><ref>PMID:19844166</ref><ref>PMID:19575011</ref><ref>PMID:20493174</ref><ref>PMID:20930849</ref><ref>PMID:20081228</ref><ref>PMID:20980437</ref><ref>PMID:21127351</ref> [[http://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN]] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.

	==About this Structure==		==About this Structure==
Line 15:		Line 17:

	==Reference==		==Reference==
	<ref group="xtra">PMID:018566585</ref><references group="xtra"/>		<ref group="xtra">PMID:018566585</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Baumli, S.]]		[[Category: Baumli, S.]]

OCA at 11:42, 20 October 2012

2012-10-20T11:42:24Z

← Older revision		Revision as of 11:42, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[3blh]] is a 2 chain structure ~~of [[Cyclin]] and [[Cyclin-dependent 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=3BLH OCA].		[[3blh]] is a 2 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=3BLH OCA].

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

OCA: Protected "3blh" [edit=sysop:move=sysop]

2012-07-26T06:19:36Z

Protected "3blh" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:19, 26 July 2012
(No difference)