Homo sapiens Protein: EIF2AK3
InnateDB Protein IDBP-60520.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol EIF2AK3
Protein Name eukaryotic translation initiation factor 2-alpha kinase 3
Synonyms PEK; PERK; WRS;
Species Homo sapiens
Ensembl Protein ENSP00000307235
InnateDB Gene IDBG-60518 (EIF2AK3)
Protein Structure
UniProt Annotation
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 (CCND1). Involved in control of mitochondrial morphology and function (By similarity). {ECO:0000250}.
Subcellular Localization Endoplasmic reticulum membrane; Single-pass type I membrane protein.
Disease Associations Wolcott-Rallison syndrome (WRS) [MIM:226980]: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities. {ECO:0000269PubMed:10932183}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity Ubiquitous. A high level expression is seen in secretory tissues.
Number of Interactions This gene and/or its encoded proteins are associated with 12 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
Experimentally validated
Total 12 [view]
Protein-Protein 11 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 1 [view]
Predicted by orthology
Total 1 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0019899 enzyme binding
GO:0019903 protein phosphatase binding
GO:0042802 identical protein binding
Biological Process
GO:0001501 skeletal system development
GO:0001503 ossification
GO:0002063 chondrocyte development
GO:0006412 translation
GO:0006468 protein phosphorylation
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006983 ER overload response
GO:0006987 activation of signaling protein activity involved in unfolded protein response
GO:0007029 endoplasmic reticulum organization
GO:0007595 lactation
GO:0009967 positive regulation of signal transduction
GO:0010629 negative regulation of gene expression
GO:0017148 negative regulation of translation
GO:0019217 regulation of fatty acid metabolic process
GO:0019722 calcium-mediated signaling
GO:0030073 insulin secretion
GO:0030282 bone mineralization
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031016 pancreas development
GO:0031018 endocrine pancreas development
GO:0031642 negative regulation of myelination
GO:0032055 negative regulation of translation in response to stress
GO:0032057 negative regulation of translational initiation in response to stress
GO:0032092 positive regulation of protein binding
GO:0032933 SREBP signaling pathway
GO:0034976 response to endoplasmic reticulum stress
GO:0043066 negative regulation of apoptotic process
GO:0044267 cellular protein metabolic process
GO:0045444 fat cell differentiation
GO:0046777 protein autophosphorylation
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0051260 protein homooligomerization
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Cellular Component
GO:0005623 cell
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
Protein Structure and Domains
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011047 Quinonprotein alcohol dehydrogenase-like superfamily
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
Post-translational Modifications
SwissProt Q9NZJ5
PhosphoSite PhosphoSite-Q9NZJ5
UniProt Splice Variant
Entrez Gene 9451
UniGene Hs.596827
RefSeq NP_004827
OMIM 604032
HPRD 04942
EMBL AC062029 AC104134 AF110146 AF193339 AF284604 AF284605 AF284606 AF284607 AF284608 AF284609 AF284610 AF284611 AF284612 AF284613 AF284614 AF284615 AK315287 BC126354 BC126356
GenPept AAD19961 AAF61199 AAF91480 AAI26355 AAI26357 AAY14777 AAY24331 BAG37696