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| | ==Structure of JMJD6 complexd with ALPHA-KETOGLUTARATE and Fab Fragment.== | | ==Structure of JMJD6 complexd with ALPHA-KETOGLUTARATE and Fab Fragment.== |
| - | <StructureSection load='3ldb' size='340' side='right' caption='[[3ldb]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3ldb' size='340' side='right'caption='[[3ldb]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ldb]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Armenian_hamster Armenian hamster] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LDB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ldb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Nothocricetulus_migratorius Nothocricetulus migratorius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LDB 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ld8|3ld8]]</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JMJD6, JMJD6 (1-403), KIAA0585, PTDSR ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3ldb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ldb OCA], [https://pdbe.org/3ldb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ldb RCSB], [https://www.ebi.ac.uk/pdbsum/3ldb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ldb ProSAT]</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=3ldb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ldb OCA], [http://pdbe.org/3ldb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ldb RCSB], [http://www.ebi.ac.uk/pdbsum/3ldb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ldb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ld/3ldb_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ld/3ldb_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> |
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| | ==See Also== | | ==See Also== |
| - | *[[Jumonji domain-containing protein|Jumonji domain-containing protein]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[3D structures of antibody|3D structures of antibody]] | + | *[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]] |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Armenian hamster]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Hong, X]] | + | [[Category: Nothocricetulus migratorius]] |
| - | [[Category: Kappler, J W]] | + | [[Category: Hong X]] |
| - | [[Category: Wang, C]] | + | [[Category: Kappler JW]] |
| - | [[Category: White, J]] | + | [[Category: Wang C]] |
| - | [[Category: Zang, J]] | + | [[Category: White J]] |
| - | [[Category: Zhang, G]] | + | [[Category: Zang J]] |
| - | [[Category: Alpha-ketoglutarate]]
| + | [[Category: Zhang G]] |
| - | [[Category: Fab fragment]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Jmj6d]]
| + | |
| Structural highlights
3ldb is a 3 chain structure with sequence from Homo sapiens and Nothocricetulus migratorius. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.7Å |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
JMJD6 is a Jumonji C domain-containing hydroxylase. JMJD6 binds alpha-ketoglutarate and iron and has been characterized as either a histone arginine demethylase or U2AF65 lysyl hydroxylase. Here, we describe the structures of JMJD6 with and without alpha-ketoglutarate, which revealed a novel substrate binding groove and two positively charged surfaces. The structures also contain a stack of aromatic residues located near the active center. The side chain of one residue within this stack assumed different conformations in the two structures. Interestingly, JMJD6 bound efficiently to single-stranded RNA, but not to single-stranded DNA, double-stranded RNA, or double-stranded DNA. These structural features and truncation analysis of JMJD6 suggest that JMJD6 may bind and modify single-stand RNA rather than the previously reported peptide substrates.
Interaction of JMJD6 with single-stranded RNA.,Hong X, Zang J, White J, Wang C, Pan CH, Zhao R, Murphy RC, Dai S, Henson P, Kappler JW, Hagman J, Zhang G Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14568-72. Epub 2010 Aug 2. PMID:20679243[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ 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
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