3krm: Difference between revisions

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==Imp1 kh34==
==Imp1 kh34==
<StructureSection load='3krm' size='340' side='right' caption='[[3krm]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
<StructureSection load='3krm' size='340' side='right'caption='[[3krm]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3krm]] is a 3 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=3KRM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KRM FirstGlance]. <br>
<table><tr><td colspan='2'>[[3krm]] is a 3 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=3KRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KRM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2BP1, CRDBP, VICKZ1, ZBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=3krm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3krm OCA], [http://pdbe.org/3krm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3krm RCSB], [http://www.ebi.ac.uk/pdbsum/3krm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3krm 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=3krm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3krm OCA], [https://pdbe.org/3krm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3krm RCSB], [https://www.ebi.ac.uk/pdbsum/3krm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3krm ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/IF2B1_HUMAN IF2B1_HUMAN]] RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Regulates mRNA stability during the integrated cellular stress response (ISR) in stress granules (SGs). Stabilizes the BTRC/FBW1A mRNA from degradation by disrupting miRNA-dependent interaction with AGO2. Identified in a HCV IRES-mediated translation complex, that enhances translation at the Hepatitis C virus (HCV) RNA-replicon via the internal ribosome entry site (IRES), but does not affect 5'cap-dependent translation. Acts as a HIV-1 retrovirus restriction factor that reduces HIV-1 assembly by inhibiting viral RNA packaging, assembly and processing of HIV-1 GAG protein on cellular membranes. Binds to mRNAs in stress granules (SGs). Binds to the stem-loop IV of the 5'-UTR and to the variable region and the poly(U-C) motif of the 3'-UTR of the HCV RNA-replicon. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulates its subcellular localization and translation. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the MYC and CD44 mRNAs and stabilizes these mRNAs. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations. Binds to the adenine-rich autoregulatory sequence (ARS) 5'-UTR of the PABPC1 mRNA and is involved in its translational repression. The RNA-binding activity to ARS is stimulated by PABPC1. Binds to the coding sequence region of BTRC/FBW1A mRNA and mediates stabilization of BTRC/FBW1A and MYC mRNAs in response to beta-catenin signaling. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation. Also involved in growth or survival of lung-cancer cells. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities (By similarity). Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA (By similarity). Binds to a conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA known as the 'zipcode' (By similarity). Promotes translocation of the beta-actin mRNA to dendrites (By similarity). May act as a regulator of mRNA transport to activated synapses in response to synaptic activity (By similarity).<ref>PMID:9891060</ref> <ref>PMID:16356927</ref> <ref>PMID:8132663</ref> <ref>PMID:10875929</ref> <ref>PMID:12024010</ref> <ref>PMID:16541107</ref> <ref>PMID:17101699</ref> <ref>PMID:16778892</ref> <ref>PMID:17255263</ref> <ref>PMID:17893325</ref> <ref>PMID:18385235</ref> <ref>PMID:19647520</ref> <ref>PMID:19029303</ref> <ref>PMID:19541769</ref> <ref>PMID:20080952</ref>
[https://www.uniprot.org/uniprot/IF2B1_HUMAN IF2B1_HUMAN] RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Regulates mRNA stability during the integrated cellular stress response (ISR) in stress granules (SGs). Stabilizes the BTRC/FBW1A mRNA from degradation by disrupting miRNA-dependent interaction with AGO2. Identified in a HCV IRES-mediated translation complex, that enhances translation at the Hepatitis C virus (HCV) RNA-replicon via the internal ribosome entry site (IRES), but does not affect 5'cap-dependent translation. Acts as a HIV-1 retrovirus restriction factor that reduces HIV-1 assembly by inhibiting viral RNA packaging, assembly and processing of HIV-1 GAG protein on cellular membranes. Binds to mRNAs in stress granules (SGs). Binds to the stem-loop IV of the 5'-UTR and to the variable region and the poly(U-C) motif of the 3'-UTR of the HCV RNA-replicon. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulates its subcellular localization and translation. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the MYC and CD44 mRNAs and stabilizes these mRNAs. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations. Binds to the adenine-rich autoregulatory sequence (ARS) 5'-UTR of the PABPC1 mRNA and is involved in its translational repression. The RNA-binding activity to ARS is stimulated by PABPC1. Binds to the coding sequence region of BTRC/FBW1A mRNA and mediates stabilization of BTRC/FBW1A and MYC mRNAs in response to beta-catenin signaling. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation. Also involved in growth or survival of lung-cancer cells. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities (By similarity). Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA (By similarity). Binds to a conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA known as the 'zipcode' (By similarity). Promotes translocation of the beta-actin mRNA to dendrites (By similarity). May act as a regulator of mRNA transport to activated synapses in response to synaptic activity (By similarity).<ref>PMID:9891060</ref> <ref>PMID:16356927</ref> <ref>PMID:8132663</ref> <ref>PMID:10875929</ref> <ref>PMID:12024010</ref> <ref>PMID:16541107</ref> <ref>PMID:17101699</ref> <ref>PMID:16778892</ref> <ref>PMID:17255263</ref> <ref>PMID:17893325</ref> <ref>PMID:18385235</ref> <ref>PMID:19647520</ref> <ref>PMID:19029303</ref> <ref>PMID:19541769</ref> <ref>PMID:20080952</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kr/3krm_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kr/3krm_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3krm ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3krm ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ZBP1 (zipcode-binding protein 1) was originally discovered as a trans-acting factor for the "zipcode" in the 3' untranslated region (UTR) of the beta-actin mRNA that is important for its localization and translational regulation. Subsequently, ZBP1 has been found to be a multifunctional regulator of RNA metabolism that controls aspects of localization, stability, and translation for many mRNAs. To reveal how ZBP1 recognizes its RNA targets, we biochemically characterized the interaction between ZBP1 and the beta-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element located within the first 28 nucleotides of the zipcode. The spacing between the RNA sequences is consistent with the structure of IMP1 KH34, the human ortholog of ZBP1, that we solved by X-ray crystallography. The tandem KH domains are arranged in an intramolecular anti-parallel pseudodimer conformation with the canonical RNA-binding surfaces at opposite ends of the molecule. This orientation of the KH domains requires that the RNA backbone must undergo an approximately 180 degrees change in direction in order for both KH domains to contact the RNA simultaneously. The RNA looping induced by ZBP1 binding provides a mechanism for specific recognition and may facilitate the assembly of post-transcriptional regulatory complexes by remodeling the bound transcript.


ZBP1 recognition of beta-actin zipcode induces RNA looping.,Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, Singer RH Genes Dev. 2010 Jan 15;24(2):148-58. PMID:20080952<ref>PMID:20080952</ref>
==See Also==
 
*[[Insulin-like growth factor 2 mRNA-binding protein|Insulin-like growth factor 2 mRNA-binding protein]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3krm" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Almo, S C]]
[[Category: Large Structures]]
[[Category: Chao, J A]]
[[Category: Almo SC]]
[[Category: Patskovsky, Y]]
[[Category: Chao JA]]
[[Category: Singer, R H]]
[[Category: Patskovsky Y]]
[[Category: Cell projection]]
[[Category: Singer RH]]
[[Category: Cytoplasm]]
[[Category: Kh domain]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Rna binding protein]]
[[Category: Rna-binding]]
[[Category: Translation regulation]]

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