2jye

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{{STRUCTURE_2jye| PDB=2jye | SCENE= }}
{{STRUCTURE_2jye| PDB=2jye | SCENE= }}
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'''Human Granulin A'''
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===Human Granulin A===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 18359860 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18359860}}
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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2JYE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JYE OCA].
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2JYE is a [[Single protein]] structure of 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].
==Reference==
==Reference==
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[[Category: Secreted]]
[[Category: Secreted]]
[[Category: Stack of hairpin]]
[[Category: Stack of hairpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:37:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:40:53 2008''

Revision as of 04:40, 29 July 2008

Image:2jye.png

Template:STRUCTURE 2jye

Contents

Human Granulin A

Template:ABSTRACT PUBMED 18359860

Disease

Known disease associated with this structure: Frontotemporal lobar degeneration with ubiquitin-positive inclusions OMIM:[138945]

About this Structure

2JYE is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

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

Page seeded by OCA on Tue Jul 29 07:40:53 2008

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