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Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''EIF2AK3''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


Function

The protein encoded by this gene
phosphorylates In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...
the alpha subunit of eukaryotic translation-initiation factor 2 (
EIF2 Eukaryotic Initiation Factor 2 (eIF2) is a eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer ...
), leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. It is a type I membrane protein located in the
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
(ER), where it is induced by ER stress caused by malfolded proteins.


Clinical significance

Patients with mutations in this gene develop Wolcott-Rallison syndrome.


Interactions

EIF2AK3 has been shown to interact with DNAJC3,
NFE2L2 Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the ''NFE2L2'' gene. NRF2 is a bZIP domain, basic leucine zipper (bZIP) protein t ...
, and
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
chaperone BiP (
Hsp70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of can ...
).


Inhibitors

* GSK2606414 * 3-Fluoro-GSK2606414


References


Further reading

* * * * * * * * * * * * * * * * * EC 2.7.11 {{gene-2-stub