2jye

From Proteopedia

(Difference between revisions)

Current revision

Human Granulin A

Structural highlights

2jye is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 10 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GRN_HUMAN Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:607485; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.^[1] ^[2] ^[3] Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:614706. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.^[4]

Function

GRN_HUMAN Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling. Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.

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

Progranulin is a secreted protein with important functions in several physiological and pathological processes, such as embryonic development, host defense, and wound repair. Autosomal dominant mutations in the progranulin gene cause frontotemporal dementia, while overexpression of progranulin promotes the invasive progression of a range of tumors, including those of the breast and the brain. Structurally, progranulin consists of seven-and-a-half tandem repeats of the granulin/epithelin module (GEM), several of which have been isolated as discrete 6-kDa GEM peptides. We have expressed all seven human GEMs using recombinant DNA in Escherichia coli. High-resolution NMR showed that only the three GEMs, hGrnA, hGrnC, and hGrnF, contain relatively well-defined three-dimensional structures in solution, while others are mainly mixtures of poorly structured disulfide isomers. The three-dimensional structures of hGrnA, hGrnC, and hGrnF contain a stable stack of two beta-hairpins in their N-terminal subdomains, but showed a more flexible C-terminal subdomain. Interestingly, of the well-structured GEMs, hGrnA demonstrated potent growth inhibition of a breast cancer cell line, while hGrnF was stimulatory. Poorly folded peptides were either weakly inhibitory or without activity. The functionally active and structurally well-characterized human hGrnA offers a unique opportunity for detailed structure-function studies of these important GEM proteins as novel members of mammalian growth factors.

Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities.,Tolkatchev D, Malik S, Vinogradova A, Wang P, Chen Z, Xu P, Bennett HP, Bateman A, Ni F Protein Sci. 2008 Apr;17(4):711-24. PMID:18359860^[5]

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

References

↑ Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006 Aug 24;442(7105):916-9. Epub 2006 Jul 16. PMID:16862116 doi:10.1038/nature05016
↑ Mukherjee O, Pastor P, Cairns NJ, Chakraverty S, Kauwe JS, Shears S, Behrens MI, Budde J, Hinrichs AL, Norton J, Levitch D, Taylor-Reinwald L, Gitcho M, Tu PH, Tenenholz Grinberg L, Liscic RM, Armendariz J, Morris JC, Goate AM. HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin. Ann Neurol. 2006 Sep;60(3):314-22. PMID:16983685 doi:10.1002/ana.20963
↑ Mukherjee O, Wang J, Gitcho M, Chakraverty S, Taylor-Reinwald L, Shears S, Kauwe JS, Norton J, Levitch D, Bigio EH, Hatanpaa KJ, White CL, Morris JC, Cairns NJ, Goate A. Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. Hum Mutat. 2008 Apr;29(4):512-21. PMID:18183624 doi:10.1002/humu.20681
↑ Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, Rossi G, Pareyson D, Mole SE, Staropoli JF, Sims KB, Lewis J, Lin WL, Dickson DW, Dahl HH, Bahlo M, Berkovic SF. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet. 2012 Jun 8;90(6):1102-7. doi: 10.1016/j.ajhg.2012.04.021. Epub, 2012 May 17. PMID:22608501 doi:10.1016/j.ajhg.2012.04.021
↑ Tolkatchev D, Malik S, Vinogradova A, Wang P, Chen Z, Xu P, Bennett HP, Bateman A, Ni F. Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities. Protein Sci. 2008 Apr;17(4):711-24. PMID:18359860 doi:http://dx.doi.org/17/4/711

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/2jye"

@@ Line 1: / Line 1: @@
 ==Human Granulin A==
-<StructureSection load='2jye' size='340' side='right' caption='[[2jye]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='2jye' size='340' side='right'caption='[[2jye]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2jye]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JYE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2jye]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JYE FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qgm|1qgm]], [[1g26|1g26]], [[1fwo|1fwo]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2jye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jye OCA], [https://pdbe.org/2jye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jye RCSB], [https://www.ebi.ac.uk/pdbsum/2jye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jye ProSAT]</span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jye RCSB], [http://www.ebi.ac.uk/pdbsum/2jye PDBsum]</span></td></tr>
+</table>
-<table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN]] Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:[http://omim.org/entry/607485 607485]]; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.<ref>PMID:16862116</ref> <ref>PMID:16983685</ref> <ref>PMID:18183624</ref>   Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:[http://omim.org/entry/614706 614706]]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.<ref>PMID:22608501</ref>
+[https://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN] Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:[https://omim.org/entry/607485 607485]; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.<ref>PMID:16862116</ref> <ref>PMID:16983685</ref> <ref>PMID:18183624</ref>   Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:[https://omim.org/entry/614706 614706]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.<ref>PMID:22608501</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN]] Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.  Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.
+[https://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN] Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.  Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jy/2jye_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jy/2jye_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>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jye ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2jye" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 34: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Chen, Z.]]
+[[Category: Large Structures]]
-[[Category: Ni, F.]]
+[[Category: Chen Z]]
-[[Category: Tolkatchev, D.]]
+[[Category: Ni F]]
-[[Category: Wang, P.]]
+[[Category: Tolkatchev D]]
-[[Category: Xu, P.]]
+[[Category: Wang P]]
-[[Category: Cytokine]]
+[[Category: Xu P]]
-[[Category: Epithelin]]
-[[Category: Glycoprotein]]
-[[Category: Granulin some]]
-[[Category: Human]]
-[[Category: Secreted]]
-[[Category: Stack of hairpin]]

2jye

From Proteopedia

Current revision

Human Granulin A

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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