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| | <StructureSection load='4z68' size='340' side='right'caption='[[4z68]], [[Resolution|resolution]] 1.86Å' scene=''> | | <StructureSection load='4z68' size='340' side='right'caption='[[4z68]], [[Resolution|resolution]] 1.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4z68]] is a 2 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=4Z68 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z68 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4z68]] is a 2 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=4Z68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z68 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNKS2, PARP5B, TANK2, TNKL ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4z68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z68 OCA], [https://pdbe.org/4z68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z68 RCSB], [https://www.ebi.ac.uk/pdbsum/4z68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z68 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=4z68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z68 OCA], [http://pdbe.org/4z68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z68 RCSB], [http://www.ebi.ac.uk/pdbsum/4z68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z68 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> | + | [https://www.uniprot.org/uniprot/ARPIN_HUMAN ARPIN_HUMAN] Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence.<ref>PMID:24132237</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]] | + | *[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Campanacci, V]] | + | [[Category: Campanacci V]] |
| - | [[Category: Cherfils, J]] | + | [[Category: Cherfils J]] |
| - | [[Category: Dang, I]] | + | [[Category: Dang I]] |
| - | [[Category: Fetics, S K]] | + | [[Category: Fetics SK]] |
| - | [[Category: Gautreau, A]] | + | [[Category: Gautreau A]] |
| - | [[Category: Actin polymerization]]
| + | |
| - | [[Category: Arp 2/3]]
| + | |
| - | [[Category: Arpin]]
| + | |
| - | [[Category: Cell migration]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
ARPIN_HUMAN Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence.[1]
Publication Abstract from PubMed
Arpin is a newly discovered regulator of actin polymerization at the cell leading edge, which steers cell migration by exerting a negative control on the Arp2/3 complex. Arpin proteins have an acidic tail homologous to the acidic motif of the VCA domain of nucleation-promoting factors (NPFs). This tail is predicted to compete with the VCA of NPFs for binding to the Arp2/3 complex, thereby mitigating activation and/or tethering of the complex to sites of actin branching. Here, we investigated the structure of full-length Arpin using synchrotron small-angle X-ray scattering, and of its acidic tail in complex with an ankyrin repeats domain using X-ray crystallography. The data were combined in a hybrid model in which the acidic tail extends from the globular core as a linear peptide and forms a primary epitope that is readily accessible in unbound Arpin and suffices to tether Arpin to interacting proteins with high affinity.
Hybrid Structural Analysis of the Arp2/3 Regulator Arpin Identifies Its Acidic Tail as a Primary Binding Epitope.,Fetics S, Thureau A, Campanacci V, Aumont-Nicaise M, Dang I, Gautreau A, Perez J, Cherfils J Structure. 2016 Jan 5. pii: S0969-2126(15)00505-5. doi:, 10.1016/j.str.2015.12.001. PMID:26774128[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dang I, Gorelik R, Sousa-Blin C, Derivery E, Guérin C, Linkner J, Nemethova M, Dumortier JG, Giger FA, Chipysheva TA, Ermilova VD, Vacher S, Campanacci V, Herrada I, Planson AG, Fetics S, Henriot V, David V, Oguievetskaia K, Lakisic G, Pierre F, Steffen A, Boyreau A, Peyriéras N, Rottner K, Zinn-Justin S, Cherfils J, Bièche I, Alexandrova AY, David NB, Small JV, Faix J, Blanchoin L, Gautreau A. Inhibitory signalling to the Arp2/3 complex steers cell migration. Nature. 2013 Nov 14;503(7475):281-4. PMID:24132237 doi:10.1038/nature12611
- ↑ Fetics S, Thureau A, Campanacci V, Aumont-Nicaise M, Dang I, Gautreau A, Perez J, Cherfils J. Hybrid Structural Analysis of the Arp2/3 Regulator Arpin Identifies Its Acidic Tail as a Primary Binding Epitope. Structure. 2016 Jan 5. pii: S0969-2126(15)00505-5. doi:, 10.1016/j.str.2015.12.001. PMID:26774128 doi:http://dx.doi.org/10.1016/j.str.2015.12.001
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