8p6i

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Current revision (09:48, 17 October 2024) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8p6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p6i OCA], [https://pdbe.org/8p6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p6i RCSB], [https://www.ebi.ac.uk/pdbsum/8p6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p6i ProSAT]</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=8p6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p6i OCA], [https://pdbe.org/8p6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p6i RCSB], [https://www.ebi.ac.uk/pdbsum/8p6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p6i ProSAT]</span></td></tr>
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</table>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.
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== Publication Abstract from PubMed ==
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== Function ==
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Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at mucosal surfaces. MUC1 has a barrier function against bacterial invasion and is well known for its aberrant expression and glycosylation in adenocarcinomas. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR are powerful research tools with applications in the diagnosis and treatment of MUC1-expressing cancers. Here, we report direct mass spectrometry-based sequencing of anti-MUC1 hybridoma-derived 139H2 IgG, enabling reverse-engineering of the functional recombinant monoclonal antibody. The crystal structure of the 139H2 Fab fragment in complex with the MUC1 epitope was solved, revealing the molecular basis of 139H2 binding specificity to MUC1 and its tolerance to O-glycosylation of the VNTR. The available sequence of 139H2 will allow further development of MUC1-related diagnostic, targeting, and treatment strategies.
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[https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref> The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref>
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Reverse-engineering the anti-MUC1 antibody 139H2 by mass spectrometry-based de novo sequencing.,Peng W, Giesbers KC, Siborova M, Beugelink JW, Pronker MF, Schulte D, Hilkens J, Janssen BJ, Strijbis K, Snijder J Life Sci Alliance. 2024 Mar 20;7(6):e202302366. doi: 10.26508/lsa.202302366. , Print 2024 Jun. PMID:38508723<ref>PMID:38508723</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8p6i" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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<references/>

Current revision

Crystal structure of the 139H2 Fab fragment bound to Muc1 peptide epitope

PDB ID 8p6i

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