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2xa6

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Structural basis for homodimerization of the Src-associated during mitosis, 68 kD protein (Sam68) Qua1 domain

Structural highlights

2xa6 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KHDR1_HUMAN Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export.^[1] ^[2] ^[3] ^[4] [UniProtKB:Q60749][UniProtKB:Q8UUW7] Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase.^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Sam68 (Src-associated during mitosis, 68 kDa) is a prototypical member of the STAR (signal transducer and activator of RNA) family of RNA-binding proteins. STAR proteins bind mRNA targets and modulate cellular processes such as cell cycle regulation and tissue development in response to extracellular signals. Sam68 has been shown to modulate alternative splicing of the pre-mRNAs of CD44 and Bcl-xL, which are linked to tumor progression and apoptosis. Sam68 and other STAR proteins recognize bipartite RNA sequences and are thought to function as homodimers. However, the structural and functional roles of the self-association are not known. Here, we present the solution structure of the Sam68 Qua1 homodimerization domain. Each monomer consists of two antiparallel alpha-helices connected by a short loop. The two subunits are arranged perpendicular to each other in an unusual four-helix topology. Mutational analysis of Sam68 in vitro and in a cell-based assay revealed that the Qua1 domain and residues within the dimerization interface are essential for alternative splicing of a CD44 minigene. Together, our results indicate that the Qua1 homodimerization domain is required for regulation of alternative splicing by Sam68.

Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain.,Meyer NH, Tripsianes K, Vincendeau M, Madl T, Kateb F, Brack-Werner R, Sattler M J Biol Chem. 2010 Sep 10;285(37):28893-901. Epub 2010 Jul 6. PMID:20610388^[8]

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

References

↑ Barlat I, Maurier F, Duchesne M, Guitard E, Tocque B, Schweighoffer F. A role for Sam68 in cell cycle progression antagonized by a spliced variant within the KH domain. J Biol Chem. 1997 Feb 7;272(6):3129-32. PMID:9013542
↑ Fusaki N, Iwamatsu A, Iwashima M, Fujisawa Ji. Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling. J Biol Chem. 1997 Mar 7;272(10):6214-9. PMID:9045636
↑ Sanchez-Margalet V, Martin-Romero C. Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway. Cell Immunol. 2001 Jul 10;211(1):30-6. PMID:11585385 doi:10.1006/cimm.2001.1815
↑ Wong G, Muller O, Clark R, Conroy L, Moran MF, Polakis P, McCormick F. Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62. Cell. 1992 May 1;69(3):551-8. PMID:1374686
↑ Barlat I, Maurier F, Duchesne M, Guitard E, Tocque B, Schweighoffer F. A role for Sam68 in cell cycle progression antagonized by a spliced variant within the KH domain. J Biol Chem. 1997 Feb 7;272(6):3129-32. PMID:9013542
↑ Fusaki N, Iwamatsu A, Iwashima M, Fujisawa Ji. Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling. J Biol Chem. 1997 Mar 7;272(10):6214-9. PMID:9045636
↑ Sanchez-Margalet V, Martin-Romero C. Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway. Cell Immunol. 2001 Jul 10;211(1):30-6. PMID:11585385 doi:10.1006/cimm.2001.1815
↑ Meyer NH, Tripsianes K, Vincendeau M, Madl T, Kateb F, Brack-Werner R, Sattler M. Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain. J Biol Chem. 2010 Sep 10;285(37):28893-901. Epub 2010 Jul 6. PMID:20610388 doi:10.1074/jbc.M110.126185

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xa6"

@@ Line 1: / Line 1: @@
 ==Structural basis for homodimerization of the Src-associated during mitosis, 68 kD protein (Sam68) Qua1 domain==
-<StructureSection load='2xa6' size='340' side='right' caption='[[2xa6]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2xa6' size='340' side='right'caption='[[2xa6]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xa6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XA6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xa6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XA6 FirstGlance]. <br>
-</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=2xa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa6 OCA], [http://pdbe.org/2xa6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xa6 RCSB], [http://www.ebi.ac.uk/pdbsum/2xa6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xa6 ProSAT]</span></td></tr>
+</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=2xa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa6 OCA], [https://pdbe.org/2xa6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xa6 RCSB], [https://www.ebi.ac.uk/pdbsum/2xa6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xa6 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/KHDR1_HUMAN KHDR1_HUMAN]] Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export.<ref>PMID:9013542</ref> <ref>PMID:9045636</ref> <ref>PMID:11585385</ref> <ref>PMID:1374686</ref> [UniProtKB:Q60749][UniProtKB:Q8UUW7]  Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase.<ref>PMID:9013542</ref> <ref>PMID:9045636</ref> <ref>PMID:11585385</ref>
+[https://www.uniprot.org/uniprot/KHDR1_HUMAN KHDR1_HUMAN] Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export.<ref>PMID:9013542</ref> <ref>PMID:9045636</ref> <ref>PMID:11585385</ref> <ref>PMID:1374686</ref> [UniProtKB:Q60749][UniProtKB:Q8UUW7]  Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase.<ref>PMID:9013542</ref> <ref>PMID:9045636</ref> <ref>PMID:11585385</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 31: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Brack-Werner, R]]
+[[Category: Large Structures]]
-[[Category: Kateb, F]]
+[[Category: Brack-Werner R]]
-[[Category: Madl, T]]
+[[Category: Kateb F]]
-[[Category: Meyer, N H]]
+[[Category: Madl T]]
-[[Category: Sattler, M]]
+[[Category: Meyer NH]]
-[[Category: Tripsianes, K]]
+[[Category: Sattler M]]
-[[Category: Vincendeaux, M]]
+[[Category: Tripsianes K]]
-[[Category: Cd44]]
+[[Category: Vincendeaux M]]
-[[Category: Cell cycle]]
-[[Category: Star protein]]
-[[Category: Transcription]]

2xa6

From Proteopedia

Current revision

Structural basis for homodimerization of the Src-associated during mitosis, 68 kD protein (Sam68) Qua1 domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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