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[[Image:1qym.gif|left|200px]]


{{Structure
==X-ray structure of human gankyrin==
|PDB= 1qym |SIZE=350|CAPTION= <scene name='initialview01'>1qym</scene>, resolution 2.80&Aring;
<StructureSection load='1qym' size='340' side='right'caption='[[1qym]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[1qym]] 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=1QYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QYM FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
|GENE= PSMD10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qym OCA], [https://pdbe.org/1qym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qym RCSB], [https://www.ebi.ac.uk/pdbsum/1qym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qym ProSAT]</span></td></tr>
|DOMAIN=
</table>
|RELATEDENTRY=
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qym OCA], [http://www.ebi.ac.uk/pdbsum/1qym PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qym RCSB]</span>
[https://www.uniprot.org/uniprot/PSD10_HUMAN PSD10_HUMAN] Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.<ref>PMID:10613832</ref> <ref>PMID:11900540</ref> <ref>PMID:11779854</ref> <ref>PMID:16023600</ref> <ref>PMID:18040287</ref> <ref>PMID:19490896</ref> <ref>PMID:19729910</ref> <ref>PMID:20628200</ref>  Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.<ref>PMID:10613832</ref> <ref>PMID:11900540</ref> <ref>PMID:11779854</ref> <ref>PMID:16023600</ref> <ref>PMID:18040287</ref> <ref>PMID:19490896</ref> <ref>PMID:19729910</ref> <ref>PMID:20628200</ref>
}}
== 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/qy/1qym_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1qym ConSurf].
<div style="clear:both"></div>


'''X-ray structure of human gankyrin'''
==See Also==
 
*[[Ankyrin 3D structures|Ankyrin 3D structures]]
 
*[[Proteasome 3D structures|Proteasome 3D structures]]
==About this Structure==
== References ==
1QYM 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=1QYM OCA].
<references/>
 
__TOC__
==Reference==
</StructureSection>
X-ray structure of human gankyrin, the product of a gene linked to hepatocellular carcinoma., Manjasetty BA, Quedenau C, Sievert V, Bussow K, Niesen F, Delbruck H, Heinemann U, Proteins. 2004 Apr 1;55(1):214-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14997555 14997555]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Buessow, K.]]
[[Category: Buessow K]]
[[Category: Delbrueck, H.]]
[[Category: Delbrueck H]]
[[Category: Heinemann, U.]]
[[Category: Heinemann U]]
[[Category: Manjasetty, B A.]]
[[Category: Manjasetty BA]]
[[Category: Niesen, F.]]
[[Category: Niesen F]]
[[Category: Quedenau, C.]]
[[Category: Quedenau C]]
[[Category: Sievert, V.]]
[[Category: Sievert V]]
[[Category: ankyrin repeat]]
[[Category: structural genomic]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:20:46 2008''

Latest revision as of 08:57, 23 August 2023

X-ray structure of human gankyrinX-ray structure of human gankyrin

Structural highlights

1qym is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PSD10_HUMAN Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.[1] [2] [3] [4] [5] [6] [7] [8] Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.[9] [10] [11] [12] [13] [14] [15] [16]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Higashitsuji H, Itoh K, Nagao T, Dawson S, Nonoguchi K, Kido T, Mayer RJ, Arii S, Fujita J. Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. Nat Med. 2000 Jan;6(1):96-9. PMID:10613832 doi:http://dx.doi.org/10.1038/71600
  2. ↑ Li J, Tsai MD. Novel insights into the INK4-CDK4/6-Rb pathway: counter action of gankyrin against INK4 proteins regulates the CDK4-mediated phosphorylation of Rb. Biochemistry. 2002 Mar 26;41(12):3977-83. PMID:11900540
  3. ↑ Dawson S, Apcher S, Mee M, Higashitsuji H, Baker R, Uhle S, Dubiel W, Fujita J, Mayer RJ. Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome. J Biol Chem. 2002 Mar 29;277(13):10893-902. Epub 2002 Jan 4. PMID:11779854 doi:http://dx.doi.org/10.1074/jbc.M107313200
  4. ↑ Higashitsuji H, Higashitsuji H, Itoh K, Sakurai T, Nagao T, Sumitomo Y, Masuda T, Dawson S, Shimada Y, Mayer RJ, Fujita J. The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. Cancer Cell. 2005 Jul;8(1):75-87. PMID:16023600 doi:http://dx.doi.org/10.1016/j.ccr.2005.06.006
  5. ↑ Chen Y, Li HH, Fu J, Wang XF, Ren YB, Dong LW, Tang SH, Liu SQ, Wu MC, Wang HY. Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export. Cell Res. 2007 Dec;17(12):1020-9. PMID:18040287 doi:http://dx.doi.org/10.1038/cr.2007.99
  6. ↑ Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T, Tanaka K, Murata S. Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones. Cell. 2009 May 29;137(5):914-25. doi: 10.1016/j.cell.2009.05.008. PMID:19490896 doi:http://dx.doi.org/10.1016/j.cell.2009.05.008
  7. ↑ Wang J, Wang XF, Zhang LG, Xie SY, Li ZL, Li YJ, Li HH, Jiao F. Involvement of the mitochondrial pathway in p53-independent apoptosis induced by p28GANK knockdown in Hep3B cells. Cytogenet Genome Res. 2009;125(2):87-97. doi: 10.1159/000227831. Epub 2009 Aug, 31. PMID:19729910 doi:http://dx.doi.org/10.1159/000227831
  8. ↑ Man JH, Liang B, Gu YX, Zhou T, Li AL, Li T, Jin BF, Bai B, Zhang HY, Zhang WN, Li WH, Gong WL, Li HY, Zhang XM. Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells. J Clin Invest. 2010 Aug;120(8):2829-41. doi: 10.1172/JCI42542. Epub 2010 Jul 12. PMID:20628200 doi:http://dx.doi.org/10.1172/JCI42542
  9. ↑ Higashitsuji H, Itoh K, Nagao T, Dawson S, Nonoguchi K, Kido T, Mayer RJ, Arii S, Fujita J. Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. Nat Med. 2000 Jan;6(1):96-9. PMID:10613832 doi:http://dx.doi.org/10.1038/71600
  10. ↑ Li J, Tsai MD. Novel insights into the INK4-CDK4/6-Rb pathway: counter action of gankyrin against INK4 proteins regulates the CDK4-mediated phosphorylation of Rb. Biochemistry. 2002 Mar 26;41(12):3977-83. PMID:11900540
  11. ↑ Dawson S, Apcher S, Mee M, Higashitsuji H, Baker R, Uhle S, Dubiel W, Fujita J, Mayer RJ. Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome. J Biol Chem. 2002 Mar 29;277(13):10893-902. Epub 2002 Jan 4. PMID:11779854 doi:http://dx.doi.org/10.1074/jbc.M107313200
  12. ↑ Higashitsuji H, Higashitsuji H, Itoh K, Sakurai T, Nagao T, Sumitomo Y, Masuda T, Dawson S, Shimada Y, Mayer RJ, Fujita J. The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. Cancer Cell. 2005 Jul;8(1):75-87. PMID:16023600 doi:http://dx.doi.org/10.1016/j.ccr.2005.06.006
  13. ↑ Chen Y, Li HH, Fu J, Wang XF, Ren YB, Dong LW, Tang SH, Liu SQ, Wu MC, Wang HY. Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export. Cell Res. 2007 Dec;17(12):1020-9. PMID:18040287 doi:http://dx.doi.org/10.1038/cr.2007.99
  14. ↑ Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T, Tanaka K, Murata S. Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones. Cell. 2009 May 29;137(5):914-25. doi: 10.1016/j.cell.2009.05.008. PMID:19490896 doi:http://dx.doi.org/10.1016/j.cell.2009.05.008
  15. ↑ Wang J, Wang XF, Zhang LG, Xie SY, Li ZL, Li YJ, Li HH, Jiao F. Involvement of the mitochondrial pathway in p53-independent apoptosis induced by p28GANK knockdown in Hep3B cells. Cytogenet Genome Res. 2009;125(2):87-97. doi: 10.1159/000227831. Epub 2009 Aug, 31. PMID:19729910 doi:http://dx.doi.org/10.1159/000227831
  16. ↑ Man JH, Liang B, Gu YX, Zhou T, Li AL, Li T, Jin BF, Bai B, Zhang HY, Zhang WN, Li WH, Gong WL, Li HY, Zhang XM. Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells. J Clin Invest. 2010 Aug;120(8):2829-41. doi: 10.1172/JCI42542. Epub 2010 Jul 12. PMID:20628200 doi:http://dx.doi.org/10.1172/JCI42542

1qym, resolution 2.80Å

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