Reviewed,
UniProtKB/Swiss-Prot Q9Z2B5 (E2AK3_MOUSE)
Last modified
January 19, 2010.
Version 93.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Eukaryotic translation initiation factor 2-alpha kinase 3 EC=2.7.11.1 Alternative name(s): PRKR-like endoplasmic reticulum kinase Pancreatic eIF2-alpha kinase | ||||
| Gene names |
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| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 1114 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin D1. Ref.5 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Enzyme regulation | Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction. |
| Subunit structure | Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells. Interacts with DNAJC3. Ref.4 Ref.6 |
| Subcellular location | Endoplasmic reticulum membrane; Single-pass type I membrane protein. |
| Tissue specificity | Ubiquitous. |
| Induction | By ER stress. |
| Domain | The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP. |
| Post-translational modification | Autophosphorylated. N-glycosylated. |
| Sequence similarities | Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. Contains 1 protein kinase domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| EIF2S1 | P05198 | 4 | EBI-1226344,EBI-1056162 | From a different organism. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 28 | 28 | Potential | ||||||
| Chain | 29 – 1114 | 1086 | Eukaryotic translation initiation factor 2-alpha kinase 3 | PRO_0000024323 | |||||
Regions | |||||||||
| Topological domain | 29 – 510 | 482 | Lumenal Potential | ||||||
| Transmembrane | 511 – 531 | 21 | Potential | ||||||
| Topological domain | 532 – 1114 | 583 | Cytoplasmic Potential | ||||||
| Domain | 589 – 1075 | 487 | Protein kinase | ||||||
| Nucleotide binding | 595 – 603 | 9 | ATP By similarity | ||||||
| Compositional bias | 48 – 51 | 4 | Poly-Ala | ||||||
| Compositional bias | 224 – 229 | 6 | Poly-Glu | ||||||
Sites | |||||||||
| Active site | 935 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 618 | 1 | ATP | ||||||
Amino acid modifications | |||||||||
| Modified residue | 711 | 1 | Phosphoserine By similarity | ||||||
| Glycosylation | 254 | 1 | N-linked (GlcNAc...) | ||||||
Experimental info | |||||||||
| Mutagenesis | 618 | 1 | K → A: Loss of activity and autophosphorylation. Ref.1 | ||||||
| Sequence conflict | 143 – 152 | 10 | VFGNKMIIPS → GTHKTSSKEC in BAB26908. Ref.3 | ||||||
| Sequence conflict | 826 | 1 | Missing in BAB22655. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase." Harding H.P., Zhang Y., Ron D. Nature 397:271-274(1999) [PubMed: 9930704] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-618. Strain: NIH Swiss. Tissue: Fibroblast. |
| [2] | Erratum Harding H.P., Zhang Y., Ron D. Nature 398:90-90(1999) |
| [3] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-152 AND 769-1114. Strain: C57BL/6J. |
| [4] | "Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response." Bertolotti A., Zhang Y., Hendershot L.M., Harding H.P., Ron D. Nat. Cell Biol. 2:326-332(2000) [PubMed: 10854322] [Abstract] Cited for: SUBUNIT. |
| [5] | "PERK mediates cell-cycle exit during the mammalian unfolded protein response." Brewer J.W., Diehl J.A. Proc. Natl. Acad. Sci. U.S.A. 97:12625-12630(2000) [PubMed: 11035797] [Abstract] Cited for: FUNCTION. |
| [6] | "Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK." Yan W., Frank C.L., Korth M.J., Sopher B.L., Novoa I., Ron D., Katze M.G. Proc. Natl. Acad. Sci. U.S.A. 99:15920-15925(2002) [PubMed: 12446838] [Abstract] Cited for: INTERACTION WITH DNAJC3. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF076681 mRNA. Translation: AAD03337.1. AK010397 mRNA. Translation: BAB26908.1. AK003226 mRNA. Translation: BAB22655.1. |
| IPI | IPI00131000. |
| PIR | T14351. |
| UniGene | Mm.247167 |
3D structure databases | |
| SMR | Q9Z2B5. Positions 100-461, 585-1077. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9Z2B5. 1 interaction. |
| STRING | Q9Z2B5. |
PTM databases | |
| PhosphoSite | Q9Z2B5. |
Proteomic databases | |
| PRIDE | Q9Z2B5. |
Genome annotation databases | |
| Ensembl | ENSMUST00000034093; ENSMUSP00000034093; ENSMUSG00000031668; Mus musculus. [Genome view] |
Organism-specific databases | |
| MGI | MGI:1341830. Eif2ak3. |
Phylogenomic databases | |
| HOGENOM | HBG356284. |
| HOVERGEN | Q9Z2B5. |
| InParanoid | Q9Z2B5. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 244. |
Gene expression databases | |
| ArrayExpress | Q9Z2B5. |
| Bgee | Q9Z2B5. |
| Genevestigator | Q9Z2B5. |
| GermOnline | ENSMUSG00000031668. Mus musculus. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR011047. Quino_AlcDH-like. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view] |
| Pfam | PF00069. Pkinase. 2 hits. [Graphical view] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| SOURCE | Search... |
Entry information
| Entry name | E2AK3_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q9Z2B5 Secondary accession number(s): Q9CTK8, Q9CWT5 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


