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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Assigned HPA protein class(es) for the encoded protein(s).
Disease related genes Enzymes Human disease related genes Potential drug targets
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
7
Cytoband
p22.1
Chromosome location (bp)
6022247 - 6059175
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions 1,2,3,4,5. Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock 6,7,8,9,10. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming 11,12,13. Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Iron deficiency also triggers activation by full-length DELE1 14. Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming 15,16. Also acts as an activator of mitophagy in response to mitochondrial damage: catalyzes phosphorylation of eIF-2-alpha (EIF2S1) following activation by S-DELE1, thereby promoting mitochondrial localization of EIF2S1, triggering PRKN-independent mitophagy 17....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Kinase, Protein synthesis inhibitor, Serine/threonine-protein kinase, Transferase
Ligand (UniProt)i
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
ATP-binding, Nucleotide-binding
Gene summary (Entrez)i
Useful information about the gene from Entrez
The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Enzymes ENZYME proteins Transferases Kinases Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Potential drug targets Human disease related genes Nervous system diseases Neurodegenerative diseases Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000166[nucleotide binding] GO:0002526[acute inflammatory response] GO:0003743[translation initiation factor activity] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004694[eukaryotic translation initiation factor 2alpha kinase activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0006413[translational initiation] GO:0006417[regulation of translation] GO:0006468[protein phosphorylation] GO:0006909[phagocytosis] GO:0008285[negative regulation of cell population proliferation] GO:0010998[regulation of translational initiation by eIF2 alpha phosphorylation] GO:0010999[regulation of eIF2 alpha phosphorylation by heme] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0017148[negative regulation of translation] GO:0020037[heme binding] GO:0030225[macrophage differentiation] GO:0042803[protein homodimerization activity] GO:0045993[negative regulation of translational initiation by iron] GO:0046501[protoporphyrinogen IX metabolic process] GO:0046777[protein autophosphorylation] GO:0046984[regulation of hemoglobin biosynthetic process] GO:0046986[negative regulation of hemoglobin biosynthetic process] GO:0051649[establishment of localization in cell] GO:0055072[iron ion homeostasis] GO:0106310[protein serine kinase activity] GO:0140467[integrated stress response signaling] GO:0140468[HRI-mediated signaling] GO:1990641[response to iron ion starvation]
Phobius predicted secreted proteins SPOCTOPUS predicted secreted proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Neurodegenerative diseases Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Neurodegenerative diseases Protein evidence (Ezkurdia et al 2014)
The Human Protein Atlas project is funded
