1yi4: Difference between revisions

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-{{Seed}}
-[[Image:1yi4.png|left|200px]]
-<!--
+==Structure of Pim-1 bound to adenosine==
-The line below this paragraph, containing "STRUCTURE_1yi4", creates the "Structure Box" on the page.
+<StructureSection load='1yi4' size='340' side='right'caption='[[1yi4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1yi4]] 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=1YI4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YI4 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-{{STRUCTURE_1yi4|  PDB=1yi4  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yi4 OCA], [https://pdbe.org/1yi4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yi4 RCSB], [https://www.ebi.ac.uk/pdbsum/1yi4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yi4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</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/yi/1yi4_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=1yi4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Pim-1 is an oncogene-encoded serine/threonine kinase primarily expressed in hematopoietic and germ cell lines. Pim-1 kinase was originally identified in Maloney murine leukemia virus-induced T-cell lymphomas and is associated with multiple cellular functions such as proliferation, survival, differentiation, apoptosis, and tumorigenesis (Wang, Z., Bhattacharya, N., Weaver, M., Petersen, K., Meyer, M., Gapter, L., and Magnuson, N. S. (2001) J. Vet. Sci. 2, 167-179). The crystal structures of Pim-1 complexed with staurosporine and adenosine were determined. Although a typical two-domain serine/threonine protein kinase fold is observed, the inter-domain hinge region is unusual in both sequence and conformation; a two-residue insertion causes the hinge to bulge away from the ATP-binding pocket, and a proline residue in the hinge removes a conserved main chain hydrogen bond donor. Without this hydrogen bond, van der Waals interactions with the hinge serve to position the ligand. The hinge region of Pim-1 resembles that of phosphatidylinositol 3-kinase more closely than it does other protein kinases. Although the phosphatidylinositol 3-kinase inhibitor LY294002 also inhibits Pim-1, the structure of the LY294002.Pim-1 complex reveals a new binding mode that may be general for Ser/Thr kinases.
-===Structure of Pim-1 bound to adenosine===
+Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002.,Jacobs MD, Black J, Futer O, Swenson L, Hare B, Fleming M, Saxena K J Biol Chem. 2005 Apr 8;280(14):13728-34. Epub 2005 Jan 17. PMID:15657054<ref>PMID:15657054</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1yi4" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15657054}}, adds the Publication Abstract to the page
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 15657054 is the PubMed ID number.
+*[[3D structures of pim-1|3D structures of pim-1]]
--->
+== References ==
-{{ABSTRACT_PUBMED_15657054}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-YI4 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=1YI4 OCA].
-==Reference==
-Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002., Jacobs MD, Black J, Futer O, Swenson L, Hare B, Fleming M, Saxena K, J Biol Chem. 2005 Apr 8;280(14):13728-34. Epub 2005 Jan 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15657054 15657054]
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Black J]]
-[[Category: Black, J.]]
+[[Category: Fleming M]]
-[[Category: Fleming, M.]]
+[[Category: Futer O]]
-[[Category: Futer, O.]]
+[[Category: Hare B]]
-[[Category: Hare, B.]]
+[[Category: Jacobs MD]]
-[[Category: Jacobs, M D.]]
+[[Category: Saxena K]]
-[[Category: Saxena, K.]]
+[[Category: Swenson L]]
-[[Category: Swenson, L.]]
-[[Category: Protein kinase]]
-[[Category: Proto oncogene]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:15:38 2008''