6mev

From Proteopedia

(Difference between revisions)

Current revision

Structure of JMJD6 bound to Mono-Methyl Arginine.

Structural highlights

6mev is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

JMJD6_HUMAN Dioxygenase that can both act as a histone arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a regulator of RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase activity, may act as a RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. Has no histone lysine demethylase activity. Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be necessary for the regulation of macrophage cytokine responses.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

More than 30% of genes in higher eukaryotes are regulated by promoter-proximal pausing of RNA polymerase II (Pol II). Phosphorylation of Pol II CTD by positive transcription elongation factor b (P-TEFb) is a necessary precursor event that enables productive transcription elongation. The exact mechanism on how the sequestered P-TEFb is released from the 7SK snRNP complex and recruited to Pol II CTD remains unknown. In this report, we utilize mouse and human models to reveal methylphosphate capping enzyme (MePCE), a core component of the 7SK snRNP complex, as the cognate substrate for Jumonji domain-containing 6 (JMJD6)'s novel proteolytic function. Our evidences consist of a crystal structure of JMJD6 bound to methyl-arginine, enzymatic assays of JMJD6 cleaving MePCE in vivo and in vitro, binding assays, and downstream effects of Jmjd6 knockout and overexpression on Pol II CTD phosphorylation. We propose that JMJD6 assists bromodomain containing 4 (BRD4) to recruit P-TEFb to Pol II CTD by disrupting the 7SK snRNP complex.

JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.,Lee S, Liu H, Hill R, Chen C, Hong X, Crawford F, Kingsley M, Zhang Q, Liu X, Chen Z, Lengeling A, Bernt KM, Marrack P, Kappler J, Zhou Q, Li CY, Xue Y, Hansen K, Zhang G Elife. 2020 Feb 12;9. pii: 53930. doi: 10.7554/eLife.53930. PMID:32048991^[6]

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

References

↑ Chang B, Chen Y, Zhao Y, Bruick RK. JMJD6 is a histone arginine demethylase. Science. 2007 Oct 19;318(5849):444-7. PMID:17947579 doi:318/5849/444
↑ Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR 3rd, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Bottger A. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science. 2009 Jul 3;325(5936):90-3. PMID:19574390 doi:325/5936/90
↑ Hahn P, Wegener I, Burrells A, Bose J, Wolf A, Erck C, Butler D, Schofield CJ, Bottger A, Lengeling A. Analysis of Jmjd6 cellular localization and testing for its involvement in histone demethylation. PLoS One. 2010 Oct 29;5(10):e13769. doi: 10.1371/journal.pone.0013769. PMID:21060799 doi:10.1371/journal.pone.0013769
↑ Mantri M, Krojer T, Bagg EA, Webby CJ, Butler DS, Kochan G, Kavanagh KL, Oppermann U, McDonough MA, Schofield CJ. Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase JMJD6. J Mol Biol. 2010 Aug 13;401(2):211-22. PMID:20684070
↑ Hong X, Zang J, White J, Wang C, Pan CH, Zhao R, Murphy RC, Dai S, Henson P, Kappler JW, Hagman J, Zhang G. Interaction of JMJD6 with single-stranded RNA. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14568-72. Epub 2010 Aug 2. PMID:20679243 doi:10.1073/pnas.1008832107
↑ Lee S, Liu H, Hill R, Chen C, Hong X, Crawford F, Kingsley M, Zhang Q, Liu X, Chen Z, Lengeling A, Bernt KM, Marrack P, Kappler J, Zhou Q, Li CY, Xue Y, Hansen K, Zhang G. JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes. Elife. 2020 Feb 12;9. pii: 53930. doi: 10.7554/eLife.53930. PMID:32048991 doi:http://dx.doi.org/10.7554/eLife.53930

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6mev"

Categories: Homo sapiens | Large Structures | Lee S | Zhang G

@@ Line 3: / Line 3: @@
 <StructureSection load='6mev' size='340' side='right'caption='[[6mev]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mev]] is a 8 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=6MEV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MEV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mev]] is a 8 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=6MEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MEV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NMM:(2S)-2-AMINO-5-[(N-METHYLCARBAMIMIDOYL)AMINO]PENTANOIC+ACID'>NMM</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]] 2.6&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JMJD6, KIAA0585, PTDSR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NMM:(2S)-2-AMINO-5-[(N-METHYLCARBAMIMIDOYL)AMINO]PENTANOIC+ACID'>NMM</scene></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=6mev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mev OCA], [http://pdbe.org/6mev PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mev RCSB], [http://www.ebi.ac.uk/pdbsum/6mev PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mev 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=6mev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mev OCA], [https://pdbe.org/6mev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mev RCSB], [https://www.ebi.ac.uk/pdbsum/6mev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mev ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/JMJD6_HUMAN JMJD6_HUMAN]] Dioxygenase that can both act as a histone arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a regulator of RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase activity, may act as a RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. Has no histone lysine demethylase activity. Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be necessary for the regulation of macrophage cytokine responses.<ref>PMID:17947579</ref> <ref>PMID:19574390</ref> <ref>PMID:21060799</ref> <ref>PMID:20684070</ref> <ref>PMID:20679243</ref>
+[https://www.uniprot.org/uniprot/JMJD6_HUMAN JMJD6_HUMAN] Dioxygenase that can both act as a histone arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a regulator of RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase activity, may act as a RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. Has no histone lysine demethylase activity. Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be necessary for the regulation of macrophage cytokine responses.<ref>PMID:17947579</ref> <ref>PMID:19574390</ref> <ref>PMID:21060799</ref> <ref>PMID:20684070</ref> <ref>PMID:20679243</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6mev" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lee, S]]
+[[Category: Lee S]]
-[[Category: Zhang, G]]
+[[Category: Zhang G]]
-[[Category: Arginine]]
-[[Category: Endopeptidase]]
-[[Category: Exopeptidase]]
-[[Category: Jumonji]]
-[[Category: Methyl]]
-[[Category: Transcription]]

6mev

From Proteopedia

Current revision

Structure of JMJD6 bound to Mono-Methyl Arginine.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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