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| | <StructureSection load='2wg3' size='340' side='right'caption='[[2wg3]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='2wg3' size='340' side='right'caption='[[2wg3]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wg3]] is a 4 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=2WG3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WG3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wg3]] is a 4 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=2WG3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WG3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wfx|2wfx]], [[2wfq|2wfq]], [[2wfr|2wfr]], [[2wft|2wft]], [[2wg4|2wg4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wg3 OCA], [http://pdbe.org/2wg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wg3 RCSB], [http://www.ebi.ac.uk/pdbsum/2wg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wg3 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=2wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wg3 OCA], [https://pdbe.org/2wg3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wg3 RCSB], [https://www.ebi.ac.uk/pdbsum/2wg3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wg3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/DHH_HUMAN DHH_HUMAN] Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:[https://omim.org/entry/607080 607080]. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.<ref>PMID:11017805</ref> Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:[https://omim.org/entry/233420 233420]; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.<ref>PMID:15356051</ref> |
| | == 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/DHH_HUMAN DHH_HUMAN] Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development. |
| | == 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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aricescu, A R]] | + | [[Category: Aricescu AR]] |
| - | [[Category: Bishop, B]] | + | [[Category: Bishop B]] |
| - | [[Category: Callaghan, C A.O]]
| + | [[Category: Harlos K]] |
| - | [[Category: Harlos, K]] | + | [[Category: Jones EY]] |
| - | [[Category: Jones, E Y]] | + | [[Category: O'Callaghan CA]] |
| - | [[Category: Siebold, C]] | + | [[Category: Siebold C]] |
| - | [[Category: Autocatalytic cleavage]] | + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Development]]
| + | |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hedgehog signaling]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Signal transduction]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
DHH_HUMAN Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.[1] Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:233420; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.[2]
Function
DHH_HUMAN Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development.
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) morphogens have fundamental roles in development, whereas dysregulation of Hh signaling leads to disease. Multiple cell-surface receptors are responsible for transducing and/or regulating Hh signals. Among these, the Hedgehog-interacting protein (Hhip) is a highly conserved, vertebrate-specific inhibitor of Hh signaling. We have solved a series of crystal structures for the human HHIP ectodomain and Desert hedgehog (DHH) in isolation, as well as HHIP in complex with DHH (HHIP-DHH) and Sonic hedgehog (Shh) (HHIP-Shh), with and without Ca2+. The interaction determinants, confirmed by biophysical studies and mutagenesis, reveal previously uncharacterized and distinct functions for the Hh Zn2+ and Ca2+ binding sites--functions that may be common to all vertebrate Hh proteins. Zn2+ makes a key contribution to the Hh-HHIP interface, whereas Ca2+ is likely to prevent electrostatic repulsion between the two proteins, suggesting an important modulatory role. This interplay of several metal binding sites suggests a tuneable mechanism for regulation of Hh signaling.
Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP.,Bishop B, Aricescu AR, Harlos K, O'Callaghan CA, Jones EY, Siebold C Nat Struct Mol Biol. 2009 Jul;16(7):698-703. Epub 2009 Jun 28. PMID:19561611[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Umehara F, Tate G, Itoh K, Yamaguchi N, Douchi T, Mitsuya T, Osame M. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. Am J Hum Genet. 2000 Nov;67(5):1302-5. Epub 2000 Oct 2. PMID:11017805 doi:S0002-9297(07)62958-9
- ↑ Canto P, Soderlund D, Reyes E, Mendez JP. Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004 Sep;89(9):4480-3. PMID:15356051 doi:10.1210/jc.2004-0863
- ↑ Bishop B, Aricescu AR, Harlos K, O'Callaghan CA, Jones EY, Siebold C. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP. Nat Struct Mol Biol. 2009 Jul;16(7):698-703. Epub 2009 Jun 28. PMID:19561611 doi:10.1038/nsmb.1607
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