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2hi3

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Revision as of 11:09, 5 January 2022

Solution structure of the homeodomain-only protein HOP

Structural highlights

2hi3 is a 1 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HOP_MOUSE] Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy.^[1] ^[2]

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

Homeodomain-only protein (HOP) is an 8-kDa transcriptional corepressor that is essential for the normal development of the mammalian heart. Previous studies have shown that HOP, which consists entirely of a putative homeodomain, acts downstream of Nkx2.5 and associates with the serum response factor (SRF), repressing transcription from SRF-responsive genes. HOP is also able to recruit histone deacetylase (HDAC) activity, consistent with its ability to repress transcription. Unlike other classic homeodomain proteins, HOP does not appear to interact with DNA, although it has been unclear if this is because of an overall divergent structure or because of specific amino acid differences between HOP and other homeodomains. To work toward an understanding of HOP function, we have determined the 3D structure of full-length HOP and used a range of biochemical assays to define the parts of the protein that are functionally important for its repression activity. We show that HOP forms a classical homeodomain fold but that it cannot recognize double stranded DNA, a result that emphasizes the importance of caution in predicting protein function from sequence homology alone. We also demonstrate that two distinct regions on the surface of HOP are required for its ability to repress an SRF-driven reporter gene, and it is likely that these motifs direct interactions between HOP and partner proteins such as SRF- and HDAC-containing complexes. Our results demonstrate that the homeodomain fold has been co-opted during evolution for functions other than sequence-specific DNA binding and suggest that HOP functions as an adaptor protein to mediate transcriptional repression.

Analysis of the structure and function of the transcriptional coregulator HOP.,Kook H, Yung WW, Simpson RJ, Kee HJ, Shin S, Lowry JA, Loughlin FE, Yin Z, Epstein JA, Mackay JP Biochemistry. 2006 Sep 5;45(35):10584-90. PMID:16939210^[3]

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

References

↑ Chen F, Kook H, Milewski R, Gitler AD, Lu MM, Li J, Nazarian R, Schnepp R, Jen K, Biben C, Runke G, Mackay JP, Novotny J, Schwartz RJ, Harvey RP, Mullins MC, Epstein JA. Hop is an unusual homeobox gene that modulates cardiac development. Cell. 2002 Sep 20;110(6):713-23. PMID:12297045
↑ Shin CH, Liu ZP, Passier R, Zhang CL, Wang DZ, Harris TM, Yamagishi H, Richardson JA, Childs G, Olson EN. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell. 2002 Sep 20;110(6):725-35. PMID:12297046
↑ Kook H, Yung WW, Simpson RJ, Kee HJ, Shin S, Lowry JA, Loughlin FE, Yin Z, Epstein JA, Mackay JP. Analysis of the structure and function of the transcriptional coregulator HOP. Biochemistry. 2006 Sep 5;45(35):10584-90. PMID:16939210 doi:10.1021/bi060641s

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hi3"

@@ Line 3: / Line 3: @@
 <StructureSection load='2hi3' size='340' side='right'caption='[[2hi3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2hi3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HI3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2hi3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HI3 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=2hi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hi3 OCA], [http://pdbe.org/2hi3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2hi3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hi3 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=2hi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hi3 OCA], [https://pdbe.org/2hi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hi3 RCSB], [https://www.ebi.ac.uk/pdbsum/2hi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hi3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/HOP_MOUSE HOP_MOUSE]] Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy.<ref>PMID:12297045</ref> <ref>PMID:12297046</ref>
+[[https://www.uniprot.org/uniprot/HOP_MOUSE HOP_MOUSE]] Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy.<ref>PMID:12297045</ref> <ref>PMID:12297046</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 27: / Line 27: @@
 </div>
 <div class="pdbe-citations 2hi3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[HOP protein|HOP protein]]
 == References ==
 <references/>

2hi3

From Proteopedia

Revision as of 11:09, 5 January 2022

Solution structure of the homeodomain-only protein HOP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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