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| | ==Crystal structure of Hedgehog-interacting protein (HHIP)== | | ==Crystal structure of Hedgehog-interacting protein (HHIP)== |
| - | <StructureSection load='3ho3' size='340' side='right' caption='[[3ho3]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='3ho3' size='340' side='right'caption='[[3ho3]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ho3]] is a 1 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=3HO3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HO3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ho3]] 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=3HO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HO3 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ho4|3ho4]], [[3ho5|3ho5]]</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]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HHIP, HHIP ORFNames: UNQ5825/PRO19644, HIP, UNQ5825/PRO19644 ([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=3ho3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ho3 OCA], [https://pdbe.org/3ho3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ho3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ho3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ho3 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=3ho3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ho3 OCA], [http://pdbe.org/3ho3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ho3 RCSB], [http://www.ebi.ac.uk/pdbsum/3ho3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ho3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HHIP_HUMAN HHIP_HUMAN]] Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.<ref>PMID:11472839</ref> <ref>PMID:19561609</ref> | + | [https://www.uniprot.org/uniprot/HHIP_HUMAN HHIP_HUMAN] Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.<ref>PMID:11472839</ref> <ref>PMID:19561609</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: Bosanac, I]] | + | [[Category: Large Structures]] |
| - | [[Category: Hymowitz, S G]] | + | [[Category: Bosanac I]] |
| - | [[Category: Cell membrane]] | + | [[Category: Hymowitz SG]] |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Egf domain]]
| + | |
| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Receptor ectodomain]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Six-bladed-propeller domain]]
| + | |
| Structural highlights
Function
HHIP_HUMAN Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.[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
Hedgehog (Hh) signaling is crucial for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hedgehog-interacting protein (Hhip) is a surface receptor antagonist that is equipotent against all three mammalian Hh homologs. The crystal structures of human HHIP alone and bound to Sonic hedgehog (SHH) now reveal that HHIP is comprised of two EGF domains and a six-bladed beta-propeller domain. In the complex structure, a critical loop from HHIP binds the pseudo active site groove of SHH and directly coordinates its Zn2+ cation. Notably, sequence comparisons of this SHH binding loop with the Hh receptor Patched (Ptc1) ectodomains and HHIP- and PTC1-peptide binding studies suggest a 'patch for Patched' at the Shh pseudo active site; thus, we propose a role for Hhip as a structural decoy receptor for vertebrate Hh.
The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling.,Bosanac I, Maun HR, Scales SJ, Wen X, Lingel A, Bazan JF, de Sauvage FJ, Hymowitz SG, Lazarus RA Nat Struct Mol Biol. 2009 Jul;16(7):691-7. Epub 2009 Jun 28. PMID:19561609[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pathi S, Pagan-Westphal S, Baker DP, Garber EA, Rayhorn P, Bumcrot D, Tabin CJ, Blake Pepinsky R, Williams KP. Comparative biological responses to human Sonic, Indian, and Desert hedgehog. Mech Dev. 2001 Aug;106(1-2):107-17. PMID:11472839
- ↑ Bosanac I, Maun HR, Scales SJ, Wen X, Lingel A, Bazan JF, de Sauvage FJ, Hymowitz SG, Lazarus RA. The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling. Nat Struct Mol Biol. 2009 Jul;16(7):691-7. Epub 2009 Jun 28. PMID:19561609 doi:10.1038/nsmb.1632
- ↑ Bosanac I, Maun HR, Scales SJ, Wen X, Lingel A, Bazan JF, de Sauvage FJ, Hymowitz SG, Lazarus RA. The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling. Nat Struct Mol Biol. 2009 Jul;16(7):691-7. Epub 2009 Jun 28. PMID:19561609 doi:10.1038/nsmb.1632
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