5a2q
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/RS18_HUMAN RS18_HUMAN]] Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA (By similarity).[HAMAP-Rule:MF_01315] [[http://www.uniprot.org/uniprot/RS24_HUMAN RS24_HUMAN]] Required for processing of pre-rRNA and maturation of 40S ribosomal subunits.<ref>PMID:18230666</ref> [[http://www.uniprot.org/uniprot/RS7_HUMAN RS7_HUMAN]] Required for rRNA maturation.<ref>PMID:19061985</ref> [[http://www.uniprot.org/uniprot/GBLP_HUMAN GBLP_HUMAN]] Involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression. Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells. Enhances phosphorylation of HIV-1 Nef by PKCs. Promotes migration of breast carcinoma cells by binding to and activating RHOA.<ref>PMID:9584165</ref> <ref>PMID:11312657</ref> <ref>PMID:11884618</ref> <ref>PMID:12958311</ref> <ref>PMID:12589061</ref> <ref>PMID:17108144</ref> <ref>PMID:17956333</ref> <ref>PMID:17244529</ref> <ref>PMID:18258429</ref> <ref>PMID:18621736</ref> <ref>PMID:18088317</ref> <ref>PMID:19785988</ref> <ref>PMID:19423701</ref> <ref>PMID:20541605</ref> <ref>PMID:20976005</ref> <ref>PMID:20573744</ref> <ref>PMID:20499158</ref> <ref>PMID:21212275</ref> <ref>PMID:21347310</ref> [[http://www.uniprot.org/uniprot/RS19_HUMAN RS19_HUMAN]] Required for pre-rRNA processing and maturation of 40S ribosomal subunits.<ref>PMID:16990592</ref> [[http://www.uniprot.org/uniprot/RS10_HUMAN RS10_HUMAN]] Component of the 40S ribosomal subunit. [[http://www.uniprot.org/uniprot/RSSA_HUMAN RSSA_HUMAN]] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate of PPP1CA. Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria.<ref>PMID:6300843</ref> <ref>PMID:16263087</ref> <ref>PMID:15516338</ref> [[http://www.uniprot.org/uniprot/RL41_HUMAN RL41_HUMAN]] Interacts with the beta subunit of protein kinase CKII and stimulates phosphorylation of DNA topoisomerase II alpha by CKII. [[http://www.uniprot.org/uniprot/RS6_HUMAN RS6_HUMAN]] May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA. [[http://www.uniprot.org/uniprot/Q6NXR8_HUMAN Q6NXR8_HUMAN]] May play a role during erythropoiesis through regulation of transcription factor DDIT3.[HAMAP-Rule:MF_03122] | [[http://www.uniprot.org/uniprot/RS18_HUMAN RS18_HUMAN]] Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA (By similarity).[HAMAP-Rule:MF_01315] [[http://www.uniprot.org/uniprot/RS24_HUMAN RS24_HUMAN]] Required for processing of pre-rRNA and maturation of 40S ribosomal subunits.<ref>PMID:18230666</ref> [[http://www.uniprot.org/uniprot/RS7_HUMAN RS7_HUMAN]] Required for rRNA maturation.<ref>PMID:19061985</ref> [[http://www.uniprot.org/uniprot/GBLP_HUMAN GBLP_HUMAN]] Involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression. Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells. Enhances phosphorylation of HIV-1 Nef by PKCs. Promotes migration of breast carcinoma cells by binding to and activating RHOA.<ref>PMID:9584165</ref> <ref>PMID:11312657</ref> <ref>PMID:11884618</ref> <ref>PMID:12958311</ref> <ref>PMID:12589061</ref> <ref>PMID:17108144</ref> <ref>PMID:17956333</ref> <ref>PMID:17244529</ref> <ref>PMID:18258429</ref> <ref>PMID:18621736</ref> <ref>PMID:18088317</ref> <ref>PMID:19785988</ref> <ref>PMID:19423701</ref> <ref>PMID:20541605</ref> <ref>PMID:20976005</ref> <ref>PMID:20573744</ref> <ref>PMID:20499158</ref> <ref>PMID:21212275</ref> <ref>PMID:21347310</ref> [[http://www.uniprot.org/uniprot/RS19_HUMAN RS19_HUMAN]] Required for pre-rRNA processing and maturation of 40S ribosomal subunits.<ref>PMID:16990592</ref> [[http://www.uniprot.org/uniprot/RS10_HUMAN RS10_HUMAN]] Component of the 40S ribosomal subunit. [[http://www.uniprot.org/uniprot/RSSA_HUMAN RSSA_HUMAN]] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate of PPP1CA. Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria.<ref>PMID:6300843</ref> <ref>PMID:16263087</ref> <ref>PMID:15516338</ref> [[http://www.uniprot.org/uniprot/RL41_HUMAN RL41_HUMAN]] Interacts with the beta subunit of protein kinase CKII and stimulates phosphorylation of DNA topoisomerase II alpha by CKII. [[http://www.uniprot.org/uniprot/RS6_HUMAN RS6_HUMAN]] May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA. [[http://www.uniprot.org/uniprot/Q6NXR8_HUMAN Q6NXR8_HUMAN]] May play a role during erythropoiesis through regulation of transcription factor DDIT3.[HAMAP-Rule:MF_03122] | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 A resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs. | ||
+ | |||
+ | Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-A resolution.,Quade N, Boehringer D, Leibundgut M, van den Heuvel J, Ban N Nat Commun. 2015 Jul 8;6:7646. doi: 10.1038/ncomms8646. PMID:26155016<ref>PMID:26155016</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
== References == | == References == | ||
<references/> | <references/> |
Revision as of 08:21, 22 July 2015
Structure of the HCV IRES bound to the human ribosome
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