2x47

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human MACROD1

Structural highlights

2x47 is a 1 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 1.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MACD1_HUMAN A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.

Function

MACD1_HUMAN Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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

Sirtuins are a family of protein lysine deacetylases, which regulate gene silencing, metabolism, life span, and chromatin structure. Sirtuins utilize NAD(+) to deacetylate proteins, yielding O-acetyl-ADP-ribose (OAADPr) as a reaction product. The macrodomain is a ubiquitous protein module known to bind ADP-ribose derivatives, which diverged through evolution to support many different protein functions and pathways. The observation that some sirtuins and macrodomains are physically linked as fusion proteins or genetically coupled through the same operon, provided a clue that their functions might be connected. Indeed, here we demonstrate that the product of the sirtuin reaction OAADPr is a substrate for several related macrodomain proteins: human MacroD1, human MacroD2, Escherichia coli YmdB, and the sirtuin-linked MacroD-like protein from Staphylococcus aureus. In addition, we show that the cell extracts derived from MacroD-deficient Neurospora crassa strain exhibit a major reduction in the ability to hydrolyze OAADPr. Our data support a novel function of macrodomains as OAADPr deacetylases and potential in vivo regulators of cellular OAADPr produced by NAD(+)-dependent deacetylation.

Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases.,Chen D, Vollmar M, Rossi MN, Phillips C, Kraehenbuehl R, Slade D, Mehrotra PV, von Delft F, Crosthwaite SK, Gileadi O, Denu JM, Ahel I J Biol Chem. 2011 Apr 15;286(15):13261-71. Epub 2011 Jan 21. PMID:21257746^[7]

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

References

↑ Meng YG, Han WD, Zhao YL, Huang K, Si YL, Wu ZQ, Mu YM. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin. Cell Res. 2007 Oct;17(10):869-80. PMID:17893710 doi:http://dx.doi.org/10.1038/cr.2007.79
↑ Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM. Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity. Endocr Relat Cancer. 2007 Sep;14(3):741-53. PMID:17914104 doi:http://dx.doi.org/10.1677/ERC-06-0082
↑ Yang J, Zhao YL, Wu ZQ, Si YL, Meng YG, Fu XB, Mu YM, Han WD. The single-macro domain protein LRP16 is an essential cofactor of androgen receptor. Endocr Relat Cancer. 2009 Mar;16(1):139-53. doi: 10.1677/ERC-08-0150. Epub 2008, Nov 20. PMID:19022849 doi:http://dx.doi.org/10.1677/ERC-08-0150
↑ Tian L, Wu Z, Zhao Y, Meng Y, Si Y, Fu X, Mu Y, Han W. Differential induction of LRP16 by liganded and unliganded estrogen receptor alpha in SKOV3 ovarian carcinoma cells. J Endocrinol. 2009 Jul;202(1):167-77. doi: 10.1677/JOE-09-0054. Epub 2009 Apr 29. PMID:19403568 doi:http://dx.doi.org/10.1677/JOE-09-0054
↑ Jankevicius G, Hassler M, Golia B, Rybin V, Zacharias M, Timinszky G, Ladurner AG. A family of macrodomain proteins reverses cellular mono-ADP-ribosylation. Nat Struct Mol Biol. 2013 Apr;20(4):508-14. doi: 10.1038/nsmb.2523. Epub 2013 Mar, 10. PMID:23474712 doi:http://dx.doi.org/10.1038/nsmb.2523
↑ Chen D, Vollmar M, Rossi MN, Phillips C, Kraehenbuehl R, Slade D, Mehrotra PV, von Delft F, Crosthwaite SK, Gileadi O, Denu JM, Ahel I. Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. J Biol Chem. 2011 Apr 15;286(15):13261-71. Epub 2011 Jan 21. PMID:21257746 doi:10.1074/jbc.M110.206771
↑ Chen D, Vollmar M, Rossi MN, Phillips C, Kraehenbuehl R, Slade D, Mehrotra PV, von Delft F, Crosthwaite SK, Gileadi O, Denu JM, Ahel I. Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. J Biol Chem. 2011 Apr 15;286(15):13261-71. Epub 2011 Jan 21. PMID:21257746 doi:10.1074/jbc.M110.206771

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2x47"

@@ Line 3: / Line 3: @@
 <StructureSection load='2x47' size='340' side='right'caption='[[2x47]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2x47]] 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=2X47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X47 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2x47]] 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=2X47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X47 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 1.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2x47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x47 OCA], [https://pdbe.org/2x47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x47 RCSB], [https://www.ebi.ac.uk/pdbsum/2x47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x47 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN]] A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.
+[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN] A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.
 == Function ==
-[[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN]] Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.<ref>PMID:17893710</ref> <ref>PMID:17914104</ref> <ref>PMID:19022849</ref> <ref>PMID:19403568</ref> <ref>PMID:23474712</ref> <ref>PMID:21257746</ref>
+[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN] Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.<ref>PMID:17893710</ref> <ref>PMID:17914104</ref> <ref>PMID:19022849</ref> <ref>PMID:19403568</ref> <ref>PMID:23474712</ref> <ref>PMID:21257746</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ahel, I]]
+[[Category: Ahel I]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Delft, F von]]
+[[Category: Edwards A]]
-[[Category: Edwards, A]]
+[[Category: Gileadi O]]
-[[Category: Gileadi, O]]
+[[Category: Krojer T]]
-[[Category: Krojer, T]]
+[[Category: Mehrotra PV]]
-[[Category: Mehrotra, P V]]
+[[Category: Phillips C]]
-[[Category: Phillips, C]]
+[[Category: Ugochukwu E]]
-[[Category: Ugochukwu, E]]
+[[Category: Vollmar M]]
-[[Category: Vollmar, M]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J]]
+[[Category: Yue W]]
-[[Category: Yue, W]]
+[[Category: Von Delft F]]
-[[Category: Estrogen signaling]]
-[[Category: Signal transduction]]
-[[Category: Signaling protein]]

2x47

From Proteopedia

Current revision

Crystal structure of human MACROD1

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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