4mzv: Difference between revisions

Revision as of 10:22, 28 December 2022

Crystal structure of extracellular part of human EpCAM

Structural highlights

4mzv 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.
Ligands:	DMU, PCA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

EPCAM_HUMAN Intestinal epithelial dysplasia;Hereditary nonpolyposis colon cancer. The disease is caused by mutations affecting the gene represented in this entry.^[1] The disease is caused by mutations affecting the gene represented in this entry. HNPCC8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.^[2]

Function

EPCAM_HUMAN May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E.^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

EpCAM (epithelial cell adhesion molecule), a stem and carcinoma cell marker, is a cell surface protein involved in homotypic cell-cell adhesion via intercellular oligomerization and proliferative signalling via proteolytic cleavage. Despite its use as a diagnostic marker and being a drug target, structural details of this conserved vertebrate-exclusive protein remain unknown. Here we present the crystal structure of a heart-shaped dimer of the extracellular part of human EpCAM. The structure represents a cis-dimer that would form at cell surfaces and may provide the necessary structural foundation for the proposed EpCAM intercellular trans-tetramerization mediated by a membrane-distal region. By combining biochemical, biological and structural data on EpCAM, we show how proteolytic processing at various sites could influence structural integrity, oligomeric state and associated functionality of the molecule. We also describe the epitopes of this therapeutically important protein and explain the antigenicity of its regions.

Crystal structure and its bearing towards an understanding of key biological functions of EpCAM.,Pavsic M, Guncar G, Djinovic-Carugo K, Lenarcic B Nat Commun. 2014 Aug 28;5:4764. doi: 10.1038/ncomms5764. PMID:25163760^[7]

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

References

↑ Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008 Aug;135(2):429-37. doi: 10.1053/j.gastro.2008.05.036. Epub, 2008 May 15. PMID:18572020 doi:https://dx.doi.org/10.1053/j.gastro.2008.05.036
↑ Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, Lee TY, Bodmer D, Hoenselaar E, Hendriks-Cornelissen SJ, Tsui WY, Kong CK, Brunner HG, van Kessel AG, Yuen ST, van Krieken JH, Leung SY, Hoogerbrugge N. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009 Jan;41(1):112-7. doi: 10.1038/ng.283. Epub 2008 Dec 21. PMID:19098912 doi:https://dx.doi.org/10.1038/ng.283
↑ Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004 Jul 29;23(34):5748-58. PMID:15195135 doi:https://dx.doi.org/10.1038/sj.onc.1207610
↑ Munz M, Zeidler R, Gires O. The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP. Cancer Lett. 2005 Jul 8;225(1):151-7. Epub 2004 Dec 28. PMID:15922867 doi:https://dx.doi.org/10.1016/j.canlet.2004.11.048
↑ Lu TY, Lu RM, Liao MY, Yu J, Chung CH, Kao CF, Wu HC. Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem. 2010 Mar 19;285(12):8719-32. doi: 10.1074/jbc.M109.077081. Epub 2010, Jan 11. PMID:20064925 doi:https://dx.doi.org/10.1074/jbc.M109.077081
↑ Ng VY, Ang SN, Chan JX, Choo AB. Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells. Stem Cells. 2010 Jan;28(1):29-35. doi: 10.1002/stem.221. PMID:19785009 doi:https://dx.doi.org/10.1002/stem.221
↑ Pavsic M, Guncar G, Djinovic-Carugo K, Lenarcic B. Crystal structure and its bearing towards an understanding of key biological functions of EpCAM. Nat Commun. 2014 Aug 28;5:4764. doi: 10.1038/ncomms5764. PMID:25163760 doi:https://dx.doi.org/10.1038/ncomms5764

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008 Aug;135(2):429-37. doi: 10.1053/j.gastro.2008.05.036. Epub, 2008 May 15. PMID:18572020 doi:https://dx.doi.org/10.1053/j.gastro.2008.05.036

[2] Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, Lee TY, Bodmer D, Hoenselaar E, Hendriks-Cornelissen SJ, Tsui WY, Kong CK, Brunner HG, van Kessel AG, Yuen ST, van Krieken JH, Leung SY, Hoogerbrugge N. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009 Jan;41(1):112-7. doi: 10.1038/ng.283. Epub 2008 Dec 21. PMID:19098912 doi:https://dx.doi.org/10.1038/ng.283

[3] Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004 Jul 29;23(34):5748-58. PMID:15195135 doi:https://dx.doi.org/10.1038/sj.onc.1207610

[4] Munz M, Zeidler R, Gires O. The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP. Cancer Lett. 2005 Jul 8;225(1):151-7. Epub 2004 Dec 28. PMID:15922867 doi:https://dx.doi.org/10.1016/j.canlet.2004.11.048

[5] Lu TY, Lu RM, Liao MY, Yu J, Chung CH, Kao CF, Wu HC. Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem. 2010 Mar 19;285(12):8719-32. doi: 10.1074/jbc.M109.077081. Epub 2010, Jan 11. PMID:20064925 doi:https://dx.doi.org/10.1074/jbc.M109.077081

[6] Ng VY, Ang SN, Chan JX, Choo AB. Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells. Stem Cells. 2010 Jan;28(1):29-35. doi: 10.1002/stem.221. PMID:19785009 doi:https://dx.doi.org/10.1002/stem.221

[7] Pavsic M, Guncar G, Djinovic-Carugo K, Lenarcic B. Crystal structure and its bearing towards an understanding of key biological functions of EpCAM. Nat Commun. 2014 Aug 28;5:4764. doi: 10.1038/ncomms5764. PMID:25163760 doi:https://dx.doi.org/10.1038/ncomms5764

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[6]

[7]

@@ Line 3: / Line 3: @@
 <StructureSection load='4mzv' size='340' side='right'caption='[[4mzv]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4mzv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MZV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4mzv]] 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=4MZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MZV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></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=4mzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mzv OCA], [https://pdbe.org/4mzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mzv RCSB], [https://www.ebi.ac.uk/pdbsum/4mzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mzv ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPCAM, GA733-2, M1S2, M4S1, MIC18, TACSTD1, TROP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mzv OCA], [http://pdbe.org/4mzv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mzv RCSB], [http://www.ebi.ac.uk/pdbsum/4mzv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mzv ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/EPCAM_HUMAN EPCAM_HUMAN]] Intestinal epithelial dysplasia;Hereditary nonpolyposis colon cancer. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:18572020</ref>   The disease is caused by mutations affecting the gene represented in this entry. HNPCC8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.<ref>PMID:19098912</ref>
+[https://www.uniprot.org/uniprot/EPCAM_HUMAN EPCAM_HUMAN] Intestinal epithelial dysplasia;Hereditary nonpolyposis colon cancer. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:18572020</ref>   The disease is caused by mutations affecting the gene represented in this entry. HNPCC8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.<ref>PMID:19098912</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/EPCAM_HUMAN EPCAM_HUMAN]] May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E.<ref>PMID:15195135</ref> <ref>PMID:15922867</ref> <ref>PMID:20064925</ref> <ref>PMID:19785009</ref>
+[https://www.uniprot.org/uniprot/EPCAM_HUMAN EPCAM_HUMAN] May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E.<ref>PMID:15195135</ref> <ref>PMID:15922867</ref> <ref>PMID:20064925</ref> <ref>PMID:19785009</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Djinovic-Carugo, K]]
+[[Category: Djinovic-Carugo K]]
-[[Category: Guncar, G]]
+[[Category: Guncar G]]
-[[Category: Lenarcic, B]]
+[[Category: Lenarcic B]]
-[[Category: Pavsic, M]]
+[[Category: Pavsic M]]
-[[Category: Cell adhesion]]
-[[Category: Dimer]]
-[[Category: Ectodomain]]
-[[Category: Extracellular space]]

4mzv: Difference between revisions

Revision as of 10:22, 28 December 2022

Crystal structure of extracellular part of human EpCAM

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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