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[[Image:1ulh.jpg|left|200px]]
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{{STRUCTURE_1ulh|  PDB=1ulh  |  SCENE=  }}
'''A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase'''


==A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase==
<StructureSection load='1ulh' size='340' side='right'caption='[[1ulh]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ulh]] is a 2 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=1ULH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ULH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</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=1ulh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ulh OCA], [https://pdbe.org/1ulh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ulh RCSB], [https://www.ebi.ac.uk/pdbsum/1ulh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ulh ProSAT], [https://www.topsan.org/Proteins/RSGI/1ulh TOPSAN]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYWC_HUMAN SYWC_HUMAN] Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.<ref>PMID:11773626</ref> <ref>PMID:1373391</ref> <ref>PMID:11773625</ref> <ref>PMID:14630953</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/ul/1ulh_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=1ulh ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human tryptophanyl-tRNA synthetase (TrpRS) is secreted into the extracellular region of vascular endothelial cells. The splice variant form (mini TrpRS) functions in vascular endothelial cell apoptosis as an angiostatic cytokine. In contrast, the closely related human tyrosyl-tRNA synthetase (TyrRS) functions as an angiogenic cytokine in its truncated form (mini TyrRS). Here, we determined the crystal structure of human mini TrpRS at a resolution of 2.3 A and compared the structure with those of prokaryotic TrpRS and human mini TyrRS. Deletion of the tRNA anticodon-binding (TAB) domain insertion, consisting of eight residues in the human TrpRS, abolished the enzyme's apoptotic activity for endothelial cells, whereas its translational catalysis and cell-binding activities remained unchanged. Thus, we have identified the inserted peptide motif that activates the angiostatic signaling.


==Overview==
A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase.,Kise Y, Lee SW, Park SG, Fukai S, Sengoku T, Ishii R, Yokoyama S, Kim S, Nureki O Nat Struct Mol Biol. 2004 Feb;11(2):149-56. Epub 2004 Jan 11. PMID:14730354<ref>PMID:14730354</ref>
Human tryptophanyl-tRNA synthetase (TrpRS) is secreted into the extracellular region of vascular endothelial cells. The splice variant form (mini TrpRS) functions in vascular endothelial cell apoptosis as an angiostatic cytokine. In contrast, the closely related human tyrosyl-tRNA synthetase (TyrRS) functions as an angiogenic cytokine in its truncated form (mini TyrRS). Here, we determined the crystal structure of human mini TrpRS at a resolution of 2.3 A and compared the structure with those of prokaryotic TrpRS and human mini TyrRS. Deletion of the tRNA anticodon-binding (TAB) domain insertion, consisting of eight residues in the human TrpRS, abolished the enzyme's apoptotic activity for endothelial cells, whereas its translational catalysis and cell-binding activities remained unchanged. Thus, we have identified the inserted peptide motif that activates the angiostatic signaling.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1ULH 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=1ULH OCA].
</div>
<div class="pdbe-citations 1ulh" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase., Kise Y, Lee SW, Park SG, Fukai S, Sengoku T, Ishii R, Yokoyama S, Kim S, Nureki O, Nat Struct Mol Biol. 2004 Feb;11(2):149-56. Epub 2004 Jan 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14730354 14730354]
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Tryptophan--tRNA ligase]]
[[Category: Ishii R]]
[[Category: Ishii, R.]]
[[Category: Kim S]]
[[Category: Kim, S.]]
[[Category: Kise Y]]
[[Category: Kise, Y.]]
[[Category: Lee SW]]
[[Category: Lee, S W.]]
[[Category: Nureki O]]
[[Category: Nureki, O.]]
[[Category: Park SG]]
[[Category: Park, S G.]]
[[Category: Sengoku T]]
[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
[[Category: Yokoyama S]]
[[Category: Sengoku, T.]]
[[Category: Yokoyama, S.]]
[[Category: Aminoacylation]]
[[Category: Angiostatic cytokine]]
[[Category: Apoptosis]]
[[Category: Riken structural genomics/proteomics initiative]]
[[Category: Rsgi]]
[[Category: Structural genomic]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 11:23:29 2008''