View source for 6uzj


==NMR structure of the HACS1 SH3 domain==
<StructureSection load='6uzj' size='340' side='right'caption='[[6uzj]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uzj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2kea 2kea]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UZJ FirstGlance]. <br>
</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=6uzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uzj OCA], [https://pdbe.org/6uzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uzj RCSB], [https://www.ebi.ac.uk/pdbsum/6uzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uzj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SAMN1_HUMAN SAMN1_HUMAN] Negative regulator of B-cell activation. Down-regulates cell proliferation (in vitro). Promotes RAC1-dependent membrane ruffle formation and reorganization of the actin cytoskeleton. Regulates cell spreading and cell polarization. Stimulates HDAC1 activity. Regulates LYN activity by modulating its tyrosine phosphorylation (By similarity).<ref>PMID:15381729</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hematopoietic adaptor containing SH3 and SAM domains-1 (HACS1) is a signaling protein with two juxtaposed protein-protein interaction domains and an intrinsically unstructured region that spans half the sequence. Here, we describe the interaction between the HACS1 SH3 domain and a sequence near the third immunoreceptor tyrosine-based inhibition motif (ITIM3) of the paired immunoglobulin receptor B (PIRB). From surface plasmon resonance binding assays using a mouse and human PIRB ITIM3 phosphopeptides as ligands, the HACS1 SH3 domain and SHP2 N-terminal SH2 domain demonstrated comparable affinities in the micromolar range. Since the PIRB ITIM3 sequence represents an atypical ligand for an SH3 domain, we determined the NMR structure of the HACS1 SH3 domain and performed a chemical shift mapping study. This study showed that the binding site on the HACS1 SH3 domain for PIRB shares many of the same amino acids found in a canonical binding cleft normally associated with polyproline ligands. Molecular modeling suggests that the respective binding sites in PIRB ITIM3 for the HACS1 SH3 domain and the SHP2 SH2 domain are too close to permit simultaneous binding. As a result, the HACS1-PIRB partnership has the potential to amalgamate signaling pathways that influence both immune and neuronal cell fate.

HACS1 signaling adaptor protein recognizes a motif in the paired immunoglobulin receptor B cytoplasmic domain.,Kwan JJ, Slavkovic S, Piazza M, Wang D, Dieckmann T, Johnson PE, Wen XY, Donaldson LW Commun Biol. 2020 Nov 13;3(1):672. doi: 10.1038/s42003-020-01397-z. PMID:33188360<ref>PMID:33188360</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6uzj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Donaldson LW]]