Protein kinase R
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
| Eukaryotic translation initiation factor 2-alpha kinase 2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Image:PBB Protein EIF2AK2 image.jpg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PDB rendering based on 1qu6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Available structures: For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
Note that theoretical models are no longer accepted in the PDB. 22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file. The current breakdown of holdings is updated weekly. File formatThrough the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.
This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects; The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs. If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction). Various funding agencies and scientific journals now require scientists to submit their structure data to PDB. Viewing the dataThe structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software. ReferencesPrinted
Online
Other external links
Links to enzyme database data
Molecular graphic visualisation tools
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
Note that theoretical models are no longer accepted in the PDB. 22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file. The current breakdown of holdings is updated weekly. File formatThrough the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.
This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects; The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs. If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction). Various funding agencies and scientific journals now require scientists to submit their structure data to PDB. Viewing the dataThe structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software. ReferencesPrinted
Online
Other external links
Links to enzyme database data
Molecular graphic visualisation tools
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
Note that theoretical models are no longer accepted in the PDB. 22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file. The current breakdown of holdings is updated weekly. File formatThrough the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.
This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects; The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs. If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction). Various funding agencies and scientific journals now require scientists to submit their structure data to PDB. Viewing the dataThe structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software. ReferencesPrinted
Online
Other external links
Links to enzyme database data
Molecular graphic visualisation tools
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symbol(s) | EIF2AK2; EIF2AK1; MGC126524; PKR; PRKR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 176871 MGI: 1353449 Homologene: 48134 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RNA expression pattern | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Image:PBB GE EIF2AK2 204211 x at tn.png | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Human | Mouse | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Entrez | 5610 | 19106 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000055332 | ENSMUSG00000024079 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uniprot | P19525 | Q78E06 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Refseq | NM_002759 (mRNA) NP_002750 (protein) | NM_011163 (mRNA) NP_035293 (protein) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Location | Chr 2: 37.18 - 37.41 Mb | Chr 17: 78.76 - 78.79 Mb | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pubmed search | [13] | [14] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Protein kinase R (Eukaryotic translation initiation factor 2-alpha kinase 2) is a protein protecting against viral infections. EIF2AK2 is its human gene.[1]
Mechanism
PKR is activated by double-stranded RNA (dsRNA), produced by virus. PKR can also be activated by the protein PACT or by heparin. PKR contains an N-terminal dsRNA binding domain (dsRBD) and a C-terminal kinase domain, that gives it pro-apoptotic (cell-killing) functions. The dsRBD consists of two tandem copies of a conserved double stranded RNA binding motif, dsRBM1 and dsRBM2. PKR is induced by interferon in a latent state. Binding to dsRNA is believed to activate PKR by inducing dimerization and subsequent autophosphorylation reactions. In situations of viral infection, the dsRNA created by viral replication and gene expression binds to the N-terminal domain, activating the protein and causing apoptosis of the cell to prevent further viral spread.
Viral defence
Viruses have developed many mechanisms to outfox the PKR mechanism. It may be done by Decoy dsRNA, degradation, hiding of virus dsRNA, dimerization block, dephosphorylation of substrate or by a pseudosubstrate.
For instance, Epstein-Barr Virus (EBV) uses the gene EBER-1 to produce decoy dsRNA. This leads to cancers such as burkitt's lymphoma, hodgkin's Disease, nasopharyngeal carcinoma and various leukemias.
| Defence type | Virus | Molecule |
|---|---|---|
| Decoy dsRNA | Adenovirus | VA RNA |
| Epstein-Barr virus | EBER | |
| HIV | TAR | |
| PKR degradation | Poliovirus | 2Apro |
| hide viral dsRNA | vaccinia virus | E3L |
| Reovirus | σ3 | |
| Influenza virus | NS1 | |
| Dimerization block | Influenza virus | p58IPK |
| hepatitis C virus | NS5A | |
| Pseudosubstrate | Vaccinia virus | K3L |
| HIV | Tat | |
| dephosphorylation of substrate | herpes simplex virus | γ134.5 |
References
Further reading
- Williams BR (1999). "PKR; a sentinel kinase for cellular stress.". Oncogene 18 (45): 6112-20. doi:10.1038/sj.onc.1203127. PMID 10557102.
- García MA, Meurs EF, Esteban M (2007). "The dsRNA protein kinase PKR: virus and cell control.". Biochimie 89 (6-7): 799-811. doi:10.1016/j.biochi.2007.03.001. PMID 17451862.
- Feng GS, Chong K, Kumar A, Williams BR (1992). "Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase.". Proc. Natl. Acad. Sci. U.S.A. 89 (12): 5447-51. PMID 1351683.
- Thomis DC, Doohan JP, Samuel CE (1992). "Mechanism of interferon action: cDNA structure, expression, and regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells.". Virology 188 (1): 33-46. PMID 1373553.
- McCormack SJ, Thomis DC, Samuel CE (1992). "Mechanism of interferon action: identification of a RNA binding domain within the N-terminal region of the human RNA-dependent P1/eIF-2 alpha protein kinase.". Virology 188 (1): 47-56. PMID 1373554.
- Mellor H, Proud CG (1991). "A synthetic peptide substrate for initiation factor-2 kinases.". Biochem. Biophys. Res. Commun. 178 (2): 430-7. PMID 1677563.
- Meurs E, Chong K, Galabru J, et al. (1990). "Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.". Cell 62 (2): 379-90. PMID 1695551.
- Silverman RH, Sengupta DN (1991). "Translational regulation by HIV leader RNA, TAT, and interferon-inducible enzymes.". J. Exp. Pathol. 5 (2): 69-77. PMID 1708818.
- Roy S, Katze MG, Parkin NT, et al. (1990). "Control of the interferon-induced 68-kilodalton protein kinase by the HIV-1 tat gene product.". Science 247 (4947): 1216-9. PMID 2180064.
- McMillan NA, Chun RF, Siderovski DP, et al. (1996). "HIV-1 Tat directly interacts with the interferon-induced, double-stranded RNA-dependent kinase, PKR.". Virology 213 (2): 413-24. doi:10.1006/viro.1995.0014. PMID 7491766.
- Cosentino GP, Venkatesan S, Serluca FC, et al. (1995). "Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo.". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9445-9. PMID 7568151.
- Barber GN, Edelhoff S, Katze MG, Disteche CM (1993). "Chromosomal assignment of the interferon-inducible double-stranded RNA-dependent protein kinase (PRKR) to human chromosome 2p21-p22 and mouse chromosome 17 E2.". Genomics 16 (3): 765-7. doi:10.1006/geno.1993.1262. PMID 7686883.
- Squire J, Meurs EF, Chong KL, et al. (1993). "Localization of the human interferon-induced, ds-RNA activated p68 kinase gene (PRKR) to chromosome 2p21-p22.". Genomics 16 (3): 768-70. doi:10.1006/geno.1993.1263. PMID 7686884.
- Prigmore E, Ahmed S, Best A, et al. (1995). "A 68-kDa kinase and NADPH oxidase component p67phox are targets for Cdc42Hs and Rac1 in neutrophils.". J. Biol. Chem. 270 (18): 10717-22. PMID 7738010.
- Barber GN, Wambach M, Wong ML, et al. (1993). "Translational regulation by the interferon-induced double-stranded-RNA-activated 68-kDa protein kinase.". Proc. Natl. Acad. Sci. U.S.A. 90 (10): 4621-5. PMID 8099444.
- Polyak SJ, Tang N, Wambach M, et al. (1996). "The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity.". J. Biol. Chem. 271 (3): 1702-7. PMID 8576172.
- Chen ZJ, Parent L, Maniatis T (1996). "Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity.". Cell 84 (6): 853-62. PMID 8601309.
- Kuhen KL, Shen X, Carlisle ER, et al. (1997). "Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog.". Genomics 36 (1): 197-201. doi:10.1006/geno.1996.0446. PMID 8812437.
- Taylor DR, Lee SB, Romano PR, et al. (1996). "Autophosphorylation sites participate in the activation of the double-stranded-RNA-activated protein kinase PKR.". Mol. Cell. Biol. 16 (11): 6295-302. PMID 8887659.
- Kuhen KL, Shen X, Samuel CE (1996). "Mechanism of interferon action sequence of the human interferon-inducible RNA-dependent protein kinase (PKR) deduced from genomic clones.". Gene 178 (1-2): 191-3. PMID 8921913.
Proteins: enzymes | |
|---|---|
| Topics | Active site - Allosteric regulation - Binding site - Catalytically perfect enzyme - Coenzyme - Cofactor - Cooperativity - EC number Enzyme catalysis - Enzyme inhibitor - Enzyme kinetics - Lineweaver-Burk plot - Michaelis-Menten kinetics - List of enzymes |
| Types | EC1 Oxidoreductases/list - EC2 Transferases/list - EC3 Hydrolases/list - EC4 Lyases/list - EC5 Isomerases/list - EC6 Ligases/list |
Phosphotransferases/kinases (EC 2.7) | |
|---|---|
| 2.7.1 - OH acceptor | Hexo- - Gluco- - Fructo- (Hepatic fructo-) - Galacto- - Phosphofructo- (1, 2) - Thymidine - NAD+ - Glycerol - Pantothenate - Mevalonate - Pyruvate - Deoxycytidine - PFP - Diacylglycerol - Bruton's tyrosine - Phosphoinositide 3 (Class I PI 3, Class II PI 3) - Sphingosine |
| 2.7.2 - COOH acceptor | Phosphoglycerate - Aspartate |
| 2.7.3 - N acceptor | Creatine |
| 2.7.4 - PO4 acceptor | Phosphomevalonate - Adenylate - Nucleoside-diphosphate |
| 2.7.6 - P2O7 | Ribose-phosphate diphosphokinase - Thiamine pyrophosphokinase |
| 2.7.7 - | |