2qob

From Proteopedia

(Difference between revisions)

Revision as of 11:37, 30 August 2023

Human EphA3 kinase domain, base structure

Structural highlights

2qob 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 1.65Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

EPHA3_HUMAN Defects in EPHA3 may be a cause of colorectal cancer (CRC) [MIM:114500.

Function

EPHA3_HUMAN Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.^[1]

Evolutionary Conservation

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

Publication Abstract from PubMed

Ephrin receptors (Eph) affect cell shape and movement, unlike other receptor tyrosine kinases that directly affect proliferative pathways. The kinase domain of EphA3 is activated by ephrin binding and receptor oligomerization. This activation is associated with two tyrosines in the juxtamembrane region; these tyrosines are sites of autophosphorylation and interact with the active site of the kinase to modulate activity. This allosteric event has important implications both in terms of understanding signal transduction pathways mediated by Eph kinases as well as discovering specific therapeutic ligands for receptor kinases. In order to provide further details of the molecular mechanism through which the unphosphorylated juxtamembrane region blocks catalysis, we studied wild-type and site-specific mutants in detail. High-resolution structures of multiple states of EphA3 kinase with and without the juxtamembrane segment allowed us to map the coupled pathway of residues that connect the juxtamembrane segment, the activation loop, and the catalytic residues of the kinase domain. This highly conserved set of residues likely delineates a molecular recognition pathway for most of the Eph RTKs, helping to characterize the dynamic nature of these physiologically important enzymes.

Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3).,Davis TL, Walker JR, Loppnau P, Butler-Cole C, Allali-Hassani A, Dhe-Paganon S Structure. 2008 Jun;16(6):873-84. PMID:18547520^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lawrenson ID, Wimmer-Kleikamp SH, Lock P, Schoenwaelder SM, Down M, Boyd AW, Alewood PF, Lackmann M. Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 2002 Mar 1;115(Pt 5):1059-72. PMID:11870224
↑ Davis TL, Walker JR, Loppnau P, Butler-Cole C, Allali-Hassani A, Dhe-Paganon S. Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure. 2008 Jun;16(6):873-84. PMID:18547520 doi:http://dx.doi.org/10.1016/j.str.2008.03.008

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qob"

@@ Line 3: / Line 3: @@
 <StructureSection load='2qob' size='340' side='right'caption='[[2qob]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2qob]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QOB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2qob]] 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=2QOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QOB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2gsf|2gsf]], [[2qo2|2qo2]], [[2qo7|2qo7]], [[2qo9|2qo9]], [[2qoc|2qoc]], [[2qod|2qod]], [[2qof|2qof]], [[2qoi|2qoi]], [[2qok|2qok]], [[2qol|2qol]], [[2qon|2qon]], [[2qoo|2qoo]], [[2qoq|2qoq]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPHA3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=2qob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qob OCA], [https://pdbe.org/2qob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qob RCSB], [https://www.ebi.ac.uk/pdbsum/2qob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qob ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/EPHA3_HUMAN EPHA3_HUMAN] Defects in EPHA3 may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].
+== Function ==
+[https://www.uniprot.org/uniprot/EPHA3_HUMAN EPHA3_HUMAN] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.<ref>PMID:11870224</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Receptor protein-tyrosine kinase]]
+[[Category: Arrowsmith CH]]
-[[Category: Arrowsmith, C H]]
+[[Category: Bochkarev A]]
-[[Category: Bochkarev, A]]
+[[Category: Butler-Cole C]]
-[[Category: Butler-Cole, C]]
+[[Category: Davis T]]
-[[Category: Davis, T]]
+[[Category: Dhe-Paganon S]]
-[[Category: Dhe-Paganon, S]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M]]
+[[Category: Mackenzie F]]
-[[Category: Mackenzie, F]]
+[[Category: Newman EM]]
-[[Category: Newman, E M]]
+[[Category: Sundstrom M]]
-[[Category: Structural genomic]]
+[[Category: Walker JR]]
-[[Category: Sundstrom, M]]
+[[Category: Weigelt J]]
-[[Category: Walker, J R]]
-[[Category: Weigelt, J]]
-[[Category: Atp-binding]]
-[[Category: Membrane]]
-[[Category: Nucleotide-binding]]
-[[Category: Phosphorylation]]
-[[Category: Receptor tyrosine kinase]]
-[[Category: Sgc]]
-[[Category: Transferase]]
-[[Category: Transmembrane]]
-[[Category: Tyrosine-protein kinase]]

2qob

From Proteopedia

Revision as of 11:37, 30 August 2023

Human EphA3 kinase domain, base structure

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox