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==Crystal Structure of PKD2 Phosphopeptide Bound to Human Class I MHC HLA-A2== | ==Crystal Structure of PKD2 Phosphopeptide Bound to Human Class I MHC HLA-A2== | ||
<StructureSection load='3bgm' size='340' side='right' caption='[[3bgm]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='3bgm' size='340' side='right'caption='[[3bgm]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3bgm]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3bgm]] is a 3 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=3BGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BGM FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bh8|3bh8]], [[3bh9|3bh9]], [[3bha|3bha]], [[3bhb|3bhb]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bh8|3bh8]], [[3bh9|3bh9]], [[3bha|3bha]], [[3bhb|3bhb]]</div></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgm OCA], [https://pdbe.org/3bgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bgm RCSB], [https://www.ebi.ac.uk/pdbsum/3bgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgm ProSAT]</span></td></tr> | ||
<table> | </table> | ||
== Disease == | == Disease == | ||
[[ | [[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[https://www.uniprot.org/uniprot/KPCD2_HUMAN KPCD2_HUMAN]] Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. In response to oxidative stress, is phosphorylated at Tyr-438 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B. In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77. Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation. During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens. In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway. During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane. Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis. In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells.<ref>PMID:15604256</ref> <ref>PMID:14743217</ref> <ref>PMID:17077180</ref> <ref>PMID:16928771</ref> <ref>PMID:17962809</ref> <ref>PMID:17951978</ref> <ref>PMID:18262756</ref> <ref>PMID:19192391</ref> <ref>PMID:19001381</ref> [[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgm_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgm_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=3bgm ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3bgm" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta-2 microglobulin|Beta-2 microglobulin]] | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | ||
*[[ | *[[MHC 3D structures|MHC 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Barrett-Wilt, G A | [[Category: Large Structures]] | ||
[[Category: Cobbold, M | [[Category: Barrett-Wilt, G A]] | ||
[[Category: Engelhard, V H | [[Category: Cobbold, M]] | ||
[[Category: Hunt, D F | [[Category: Engelhard, V H]] | ||
[[Category: Mohammed, F | [[Category: Hunt, D F]] | ||
[[Category: Salim, M | [[Category: Mohammed, F]] | ||
[[Category: Shabanowitz, J | [[Category: Salim, M]] | ||
[[Category: Willcox, B E | [[Category: Shabanowitz, J]] | ||
[[Category: Zarling, A L | [[Category: Willcox, B E]] | ||
[[Category: Zarling, A L]] | |||
[[Category: Anchor residue]] | [[Category: Anchor residue]] | ||
[[Category: Glycoprotein]] | [[Category: Glycoprotein]] | ||
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[[Category: Phosphoprotein]] | [[Category: Phosphoprotein]] | ||
[[Category: Phosphoserine]] | [[Category: Phosphoserine]] | ||
[[Category: Polymorphism]] | |||
[[Category: Serine/threonine-protein kinase]] | [[Category: Serine/threonine-protein kinase]] | ||
[[Category: Transmembrane]] | [[Category: Transmembrane]] | ||
[[Category: Tumor antigen]] | [[Category: Tumor antigen]] | ||
[[Category: Ubl conjugation]] |