View source for 2jyt


==Human Granulin C, isomer 1==
<StructureSection load='2jyt' size='340' side='right'caption='[[2jyt]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jyt]] 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=2JYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JYT FirstGlance]. <br>
</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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jyt OCA], [https://pdbe.org/2jyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jyt RCSB], [https://www.ebi.ac.uk/pdbsum/2jyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jyt ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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/2jyt_consurf.spt"</scriptWhenChecked>
    <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/main_output.php?pdb_ID=2jyt ConSurf].
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== 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<ref>PMID:18359860</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen Z]]
[[Category: Ni F]]
[[Category: Tolkatchev D]]
[[Category: Wang P]]
[[Category: Xu P]]