Gene	Activators and partners (Binding interactions are from Entrez gene data, unless specified)	Downstream effects
EIF2AK1 (HRI) eukaryotic translation initiation factor 2-alpha kinase 1	Activated by heme deficiency (cf HMBSS , nitric oxide (NOS1BS, NOS3 B) oxidative stress, arsenite and lead: inhibited by carbon monoxide (Yun et al. 2005;Sarkar et al. 2005) .	Phosphorylates EIF2alpha (EIF2S1,2 or3). Important in alpha and beta globin protein synthesis in erythroid cells (Han et al. 2001).
EIF2AK2 (PKR) eukaryotic translation initiation factor 2-alpha kinase 2 OMIM Biocarta	Activated by viral double-stranded DNA (measles, mumps, rubella, influenza, etc) (Russell 2002).  Activated by IL1B BS and TNF BS (Kaempfer 2003) (Williams 2001)and by interferons (Williams 1999). Binds to and phosphorylates TP53S (Cuddihy et al. 1999)	Phosphorylates EIF2alpha (EIF2S1,2 or3). PKR activation leads to the production of inflammatory cytokines (IL1B BS and TNF BS ) (Williams 2001). Interferon use is associated with bipolar symptoms and psychiatric disturbances (Greenberg et al. 2000;Constant et al. 2005)
EIF2AK3 (PERK) eukaryotic translation initiation factor 2-alpha kinase 3 OMIM	Activated by endoplasmic reticulum stress which is promoted by problems in protein glycosylation, sorting folding, or degradation (Cullinan and Diehl 2006).  Binds to HSPA5B.  Activated by Herpes simplex(Cheng et al. 2005): Inhibited by Hepatitis C envelope protein (Pavio et al. 2003)	Phosphorylates EIF2alpha (EIF2S1,2 or3). Phosphorylates and activates NFE2L2(Cullinan and Diehl 2005).
EIF2AK4 (GCN2) eukaryotic translation initiation factor 2-alpha kinase 4 OMIM	Activated by amino acid starvation (Hinnebusch 1994).	Phosphorylates EIF2alpha (EIF2S1,2 or3). LTP is impaired in GCN2 knockout mice (Costa-Mattioli et al. 2005)
ATF4 Sactivating transcription factor 4 (CREB-2) OMIM	Downstream target of EIF2alpha kinase activation (Rutkowski and Kaufman 2003).  Binds to DISC1 BS, GABBR1 S, PTGS2 S and to NFE2L1, NFE2L2, inter alia.	Effects on oxidative defence, apoptosis, and chaperones are mediated via interactions with DDIT3, NFE2L1,2,  and HERPUD1.  Controls GCHI B expression.
ATF5 activating transcription factor 5 OMIM	Binds to DISC1 BS  and GABBR1 S	ATF5 plays an important role in the differentiation of neurones, astrocytes and oligodendrocytes (Angelastro et al. 2003;Angelastro et al. 2005;Mason et al. 2005).
NFE2L1 nuclear factor (erythroid-derived 2)-like 1 OMIM	Binds to ATF4S.	Overexpression increases cellular glutathione levels and transactivates the gamma-glutamylcysteine synthetase (GCS) heavy subunit promoter (Myhrstad et al. 2001). Controls TNF BS expression Novotny et al, 1998
NFE2L2 nuclear factor (erythroid-derived 2)-like 2 OMIM	Binds to ATF4: Phosphorylated and inhibited by GSK3B B (Salazar et al. 2006).  Phosphorylated and activated by perk (EIF2AK3) (Cullinan and Diehl 2005) . Effects suppressed by TP53S Faraonio et al, 2006	Controls the expression of glutathione and quinone-related genes (Lee et al. 2003b) and: -
		Bipolar genes BDNF BS, G6PD B (Lee et al. 2003b;Lee et al. 2003c)	Schizophrenia genes BDNF BS, CHGB S, GABBR1 S, GCLM S,GSTM1 S,NQO2 S, (Lee et al. 2003b;Lee et al. 2003c) HMBS S (Johnsen et al. 1996)
DDIT3 DNA-damage-inducible transcript 3 (alias CEBPZ, CHOP, CHOP10, GADD153) OMIM	Activated by ATF4S (Wek et al. 2006).  TP53 S binds to promoter.  Activated by NRG1 BS in epithelial cells and by NMDA receptorBS activation during hippocampal LTP (Matsuo et al. 2000).	Increased DDIT3 expression results in glutathione depletion, increased production of reactive oxygen species and downregulation of bcl2.(McCullough et al. 2001) Controls the expression of genes related to apoptosis, cell proliferation, adhesion, protein processing (proteasome), and SOD2 S expression (You et al. 2003)
HERPUD1 (Alias Herp, mif1) homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 OMIM	Activated by endoplasmic reticulum stress and other stressors (Ma and Hendershot 2004)	.Forms a complex with elements of the endoplasmic reticulum associated protein degradation pathway (ERAD) (see Biocarta) with a proposed role in ubiquitinylation and export of proteins from the endoplasmic reticulum ; These steps are necessary for the degradation of proteins by the proteasomal complex  (Schulze et al. 2005) . Induced by homocysteine (Kokame et al. 2000), high levels of which have been associated with both biplar disorder and schizophrenia (Levine et al. 2005;Osher et al. 2004). (cf MTHFR BS).  Interacts with presenilins (Sai et al. 2002)which cleave the NRG1 BS receptor ERBB4 S (Sardi et al. 2006).
PPP1R15A(alias Gadd34) protein phosphatase 1, regulatory (inhibitor) subunit 15A	Activated by apoptotic stimuli including TNF BS. Inhibited by herpes simplex virus (Hollander et al. 2001)	Dephosphorylates EIF2alpha, a prerequisite for recovery from translational repression (Novoa et al. 2003)
ATF6 activating transcription factor 6 OMIM	Activated by endoplasmic reticulum stress: released from the endoplasmic reticulum by HSPA5 B (Xu et al. 2005).	Controls the expression of proteins concerned with protein folding, and molecular chaperones including HSPA5 B Okada et al, 2002
XBP1 BSX-box binding protein 1 OMIM	Activated by endoplasmic reticulum stress via ATF6, which is released from  the endoplasmic reticulum by HSPA5 B (Xu et al. 2005).	Controls the expression of ER resident proteins that regulate heat shock protein and chaperone activity and the endoplasmic reticulum associated degradation pathway (Lee et al. 2003a).

eIF2alpha and eIF2beta

eIF2-alpha(3 subunits)	Binding partners and other effects (from Entrez Gene Interaction summaries unless indicated)	Diseases
EIF2S1 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa	-	Mutant mice become diabetic and obese on a high fat diet Scheuner et al, 2005: No Human disease OMIM
EIF2S2 eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa	Interacts with casein kinase 2 alpha (CSNK2A1) and beta (CSNK2B) and NCK1.	No Human disease OMIM
EIF2S3 eukaryotic translation initiation factor 2, subunit 3 gamma, 52kDa	Interacts with CTCF, H3F3A and METAP2METAP2	No Human disease OMIM
eIFf2beta (5 subunits form a multicomplex) EIF2B1 eukaryotic translation initiation factor 2B, subunit 1 alpha, 26kDa	Binds to carboxy terminus of alpha (ADRA2A, ADRA2B, ADRA2C) and beta (ADRB2) adrenoceptors Klein et al, 1997	Vanishing White matter disease (OMIM) Mutations in any of these 5 subunits can provoke white matter lesions VWM PUBMED
EIF2B2 eukaryotic translation initiation factor 2B, subunit 2 beta, 39kDa	Binds to NCK1 which is able to affect protein translation Kebache et al, 2002. NCK1 is an adaptor protein for growth factor signalling and aids in eIF2alpha dephosphorylation Latreille and Larose,2006
EIF2B3 eukaryotic translation initiation factor 2B, subunit 3 gamma, 58kDa	EIF2B1-5 form a multicomplex
EIF2B4 eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDa	" "
EIF2B5 eukaryotic translation initiation factor 2B, subunit 5 epsilon, 82kDa	Phosphorylated by GSK3B B casein kinase 1 and casein kinase 2 Wang et al, 2001

 

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