InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EIF2AK3

Summary

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.

Comments

Interactions

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]
RNA-RNA	0
DNA-RNA	0

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

PDB ID

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
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt