View source for 12uo


==BCL11B ZF2-3 in Complex with a DNA Sequence Observed in the Human Globin Locus Containing Motif TGGCCA (Oligo 4-3)-C2 Form==
<StructureSection load='12uo' size='340' side='right'caption='[[12uo]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[12uo]] is a 8 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=12UO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=12UO 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]] 3.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=12uo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=12uo OCA], [https://pdbe.org/12uo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=12uo RCSB], [https://www.ebi.ac.uk/pdbsum/12uo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=12uo ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BC11B_HUMAN BC11B_HUMAN] Intellectual disability-speech delay-dysmorphic features-T cell abnormalities syndrome. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/BC11B_HUMAN BC11B_HUMAN] Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC-rich response element (By similarity). May also function in the P53-signaling pathway (By similarity).[UniProtKB:Q99PV8]<ref>PMID:16809611</ref> <ref>PMID:27959755</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
B-cell leukemia/lymphoma 11B (BCL11B), despite its name, is a key regulator of T-cell development, specification, and T-cell malignancies. BCL11B contains a bipartite DNA binding domain composed of two C2H2 zinc finger arrays: low-affinity ZF2-3 and high affinity ZF4-6. These arrays function as homotypic modules that recognize similar six-nucleotide motifs, TG(N)CC(C/T/A), as seven of the eight DNA base-contacting residues are conserved between them. The most conserved interactions involve GG dinucleotides, contacted by arginine and lysine residues at key base-interacting positions in ZF3 and ZF5. The two ZF arrays are connected by a long ~300-residue linker that provides flexibility in how the arrays engage DNA, allowing ZF2-3 and ZF4-6 binding to the same or opposite strands with variable orientation, spacing and positioning along the DNA. This extended linker is enriched in serine/threonine, acidic residues (aspartate/glutamate), and structural residues (glycine/proline), providing additional layers of transcriptional regulation possibly through post-translational modification, electrostatic modulation, and/or condensate formation. We also examined six missense mutations in base-interacting residues, that are associated with neurodevelopmental disorders. Substitutions replacing bulky, positively charged arginine or lysine with smaller or hydrophobic residues likely reduce DNA-binding affinity and/or specificity, whereas substitutions between asparagine and lysine may alter base recognition preferences.

Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.,Lee J, Zhou J, Horton JR, Yu M, Muoghalu MD, Khan FA, Zhang X, Huang Y, Blumenthal RM, Zhang X, Cheng X bioRxiv [Preprint]. 2026 May 2:2026.05.01.721897. doi: , 10.64898/2026.05.01.721897. PMID:42232506<ref>PMID:42232506</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 12uo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng X]]
[[Category: Horton JR]]
[[Category: Lee J]]
[[Category: Zhou J]]