EIF2AK4 source guide

Publication caches preserve the normal acquisition output. Separately recovered original text can provide more experimental detail than a committed abstract-only cache. A cache marked full text can still omit Methods or supplements. The accounts below state the actual scope used; no figure-image interpretation or separately downloaded supplement analysis is asserted. Bibliographic verification is distinct from verification of every annotation attributed to a paper.

Literature and access

PMID:1739968

Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast.

Cache: publications/PMID_1739968.md (SHA256 9a7318c593df4d1b286f51dcbf2e6cac30d4e93f1d419b0490ef5268142d28c6).

The official bibliographic/abstract record and exact yeast donor annotations support GCN2-mediated eIF2alpha phosphorylation and gene-specific translational control. The original body was not independently reconstructed; no detailed human enzyme assay is attributed to it. The existing main publication cache is reused unchanged.

Original source; PubMed metadata.

Operative locators: Official bibliographic/abstract record and yeast donor annotations; original body not independently reconstructed.

PMID:2038314

Ribosome association of GCN2 protein kinase, a translational activator of the GCN4 gene of Saccharomyces cerevisiae.

Cache: publications/PMID_2038314.md (SHA256 d2747ec0e8da194477a2074907c6605c542227d26c131a64319028783f3bdc8f).

The verified original abstract and exact yeast donor record support ribosome association, including salt-sensitive association rather than obligatory structural ribosome membership. The full original body was not recovered. Mammalian association evidence is kept separate from this yeast experiment.

Original source; PubMed metadata.

PMID:10504407

Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase.

Cache: publications/PMID_10504407.md (SHA256 e086c1d0a2a327f173eaea33cd3bcd2f1fe742bb2b5a4d08b2f9b96036632cc1).

Publisher-indexed Methods, Results and Discussion establish mouse GCN2 kinase activity on human eIF2alpha, including the Ser51 substrate control. The enzyme is mouse AJ243533 expressed in human 293/293T cells; the human GCN2 sequence reported here is only a 548-residue EST-derived fragment. The unchanged publication cache is abstract-only. No direct full-length human GCN2 or natural-product equivalence is inferred.

Original source; PubMed metadata.

Operative locators: Original Methods, Results and Discussion; Figures 3–5; indexed publisher lines 160–196 and 247–295.

PMID:12176355

Activation of GCN2 in UV-irradiated cells inhibits translation.

Cache: publications/PMID_12176355.md (SHA256 d84d0d238993f3e12ce08c1267bd90a90bb76a783e915a52a21f25416a846356).

Indexed original Methods and Results establish UV-induced GCN2-dependent eIF2alpha phosphorylation and translation attenuation in mouse fibroblasts. A cell-cycle effect is discussed as a possible consequence; these assays do not establish the human DNA-damage-checkpoint transfer. The normal cache remains abstract-only despite separate original-text access.

Original source; PubMed metadata.

Operative locators: Original selected Results, Methods and Discussion; mouse fibroblast UV experiments and proposed cell-cycle interpretation.

PMID:16054071

The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores.

Cache: publications/PMID_16054071.md (SHA256 77b316dc3c64b0408fb20ff911051cce91695d57fce41796dc82130cf8f575ad).

Verified bibliographic/abstract record and selected original summary and beginning of Results support mouse GCN2-dependent feeding responses to amino-acid imbalance. Complete Methods were not recovered. Retains the curator-supported organismal context without claiming a directly tested human feeding circuit.

Original source; PubMed metadata.

Operative locators: Abstract, original summary and beginning of Results; complete Methods unavailable.

PMID:16121183

Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2.

Cache: publications/PMID_16121183.md (SHA256 7ac06c9a2d220b71f713a127c0efb39ff493e9c484ab0f1443c3e4519efbb98c).

Original Methods, Results and captions establish mouse GCN2-knockout effects whose direction depends on stimulation or training strength. Weak stimulation/training enhances plasticity or memory, whereas stronger protocols reveal impaired late plasticity or memory. Human GCN2 antigen used to raise an antibody is not a human functional experiment.

Original source; PubMed metadata.

Operative locators: Original Methods for mouse genetics, electrophysiology, behavioral testing and polysomes; selected Results and Discussion comparing weak and strong protocols.

PMID:16601681

Antiviral effect of the mammalian translation initiation factor 2alpha kinase GCN2 against RNA viruses.

Cache: publications/PMID_16601681.md (SHA256 ec79a5c87b2c0751fc52eedabef05e16d97510909551c48d52fb266f72bb1312).

Original Methods and Results identify mouse GCN2 constructs despite their human expression host. Kinase and tRNA-regulatory controls support the conserved stress mechanism and antiviral translation restriction. The direct Northwestern probe is viral GAR RNA; it is not a direct tRNA-binding assay. Mouse infection and cellular results are kept distinct.

Original source; PubMed metadata.

Operative locators: Original Methods, selected Results and Discussion; Figure 1 activation experiments and Figure 2 RNA-probe experiments.

PMID:17369398

A novel checkpoint mechanism regulating the G1/S transition.

Cache: publications/PMID_17369398.md (SHA256 3637d49d0c3778c995dfca132fc51589c0ecaca1b0d591fef98623009209ce19).

Verified source linked from InterPro IPR016255 and selected original text concern a fungal G1/S checkpoint mechanism. The family assignment is valid, but conservation of kinase chemistry alone does not establish the same checkpoint role in human EIF2AK4. The newly acquired normal cache is not being represented as an additional complete operative-body read.

Original source; PubMed metadata.

PMID:19033384

The G1-S checkpoint in fission yeast is not a general DNA damage checkpoint.

Cache: publications/PMID_19033384.md (SHA256 3f7eaddc4e61428cd098ad68dc09d69a738edd0f8a13cda22c3a18779ea05c7b).

Verified PubMed abstract and selected indexed Results qualify the fungal checkpoint model: the G1/S response is stimulus-dependent rather than a general DNA-damage checkpoint. Complete operative Methods were not accessible. This qualification does not show that GCN2 lacks all checkpoint functions.

Original source; PubMed metadata.

Operative locators: PubMed abstract and selected original Results on stimulus specificity; complete Methods unavailable.

PMID:23447528

IMPACT is a developmentally regulated protein in neurons that opposes the eukaryotic initiation factor 2α kinase GCN2 in the modulation of neurite outgrowth.

Cache: publications/PMID_23447528.md (SHA256 88202744c3808e2ab297bbbcd561875fbbd1f737a3e86e05ee6a97239ee3233a).

Original Methods and Results in mouse primary neurons and N2a cells support inhibition of neurite outgrowth by GCN2 and its modulation by IMPACT. The unchanged NeuN differentiation-marker result limits a broader differentiation claim. Polysome association is a separate observation; no direct human neuronal assay or universal stable ribosome membership is inferred.

Original source; PubMed metadata.

Operative locators: Original Methods and selected neuronal Results, captions and Discussion, including morphometry and the NeuN marker.

PMID:24310610

Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.

Cache: publications/PMID_24310610.md (SHA256 5f38785457c349266a155d545d0f6c7b34564a05bed0e330f216afbe22da3df9).

Available main text distinguishes human dendritic-cell signaling observations from mouse vaccine and cross-presentation experiments. The positive immune context is retained without assigning a T-cell-intrinsic mechanism. The normal cache contains main text but omits Methods and supplementary material, so its full-text flag is not treated as complete experimental access.

Original source; PubMed metadata.

Operative locators: Available main-text blocks 10–26; Methods and separately published supplements not available in this cache.

PMID:25329545

p58IPK is an inhibitor of the eIF2α kinase GCN2 and its localization and expression underpin protein synthesis and ER processing capacity.

Cache: publications/PMID_25329545.md (SHA256 5a3f649d384174f3e64056eb45b905ed0582de801e5d37d31f2546a8e2ddcd0b).

Bibliographic identity and the abstract identify GCN2 inhibition by p58IPK. Only a selected original caption was additionally accessible; the operative cold-response experiment was not recovered. The cold-response assertion remains unresolved. Central kinase and amino-acid stress claims have independent support; this does not reconstruct this paper's unavailable Methods.

Original source; PubMed metadata.

PMID:26102367

Translational Upregulation of an Individual p21Cip1 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress.

Cache: publications/PMID_26102367.md (SHA256 7e78a9a12bb7b4098ba28d3305b4849413c3e38fc383061f52d90e56c153683f).

Operative original Methods and Results distinguish human SQ20B GCN2-depletion experiments from mouse p21 transcript reporters and translation analyses. Supports GCN2-dependent eIF2alpha phosphorylation during leucine limitation and selective p21 transcript translation alongside bulk translational inhibition. Does not assign activity to each natural human GCN2 product.

Original source; PubMed metadata.

Operative locators: Selected original Methods, Results and associated captions; indexed blocks 7–14, 19–28, 32–34, 38, 40, 45, 47, 49, 51, 53 and 55.

PMID:32610081

Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate.

Cache: publications/PMID_32610081.md (SHA256 98f8f521abae485759b06ef3838a28f559718588d9722d59308dffa088aa67f3).

Human MCF10A GCN2 inhibition and shRNA establish collision-induced eIF2alpha phosphorylation dependence. Kinase-dead ZAKalpha rescues this branch, whereas simple glutamine-starvation signaling persists in ZAK-knockout cells. The original did not capture GCN2 or GCN20 on collided ribosomes. Selected Methods, Results and captions were read; supplement files were not inspected. This is cellular signaling evidence, not a purified human enzyme or isoform-resolved experiment.

Original source; PubMed metadata.

Operative locators: Original Results paragraphs P21/P22, P26–P28 and P35–P37; Figures 4, 5 and 7; Methods P44–P53; embedded supplementary captions P66, P67 and P69.

PMID:39947182

The integrated stress response regulates 18S nonfunctional rRNA decay in mammals.

Cache: publications/PMID_39947182.md (SHA256 de134a10c98b644d612393a45e61595e3e044be2e7c643955181394d02b0f9bf).

Operative main text and Methods support human GCN2 knockout and wild-type versus kinase-dead rescue, eIF2alpha-dependent initiation control and downstream rRNA quality control. RNF10 performs the ubiquitination. Failure to capture GCN2 on ribosomes is specific to the tested preparation, not a universal absence of association. No GCN2 ubiquitin-ligase or direct RNA-degradation chemistry is inferred.

Original source; PubMed metadata.

Operative locators: Selected original Methods and Results; cache blocks 31–33, 36–37, 40–43, 46, 49–50, 53–54, 70–72, 96, 101–102, 139, 151 and 157.

Annotation and computational provenance

The 53 raw GOA records seed 52 distinct full source contexts; one context is repeated in the raw response. All imported source objects are retained without lifecycle edits. The following index is zero-based and corresponds to the review and bundled source-contexts.json.

Index Term Evidence and source Decision
0 GO:0000049 tRNA binding ISS; GO_REF:0000024 ACCEPT
1 GO:0000077 DNA damage checkpoint signaling IEA; GO_REF:0000002 UNDECIDED
2 GO:0002230 positive regulation of defense response to virus by host ISS; GO_REF:0000024 KEEP_AS_NON_CORE
3 GO:0002286 T cell activation involved in immune response ISS; GO_REF:0000024 KEEP_AS_NON_CORE
4 GO:0002821 positive regulation of adaptive immune response ISS; GO_REF:0000024 KEEP_AS_NON_CORE
5 GO:0004672 protein kinase activity IDA; PMID:25329545 MODIFY
6 GO:0004672 protein kinase activity IEA; GO_REF:0000002 MODIFY
7 GO:0004674 protein serine/threonine kinase activity IEA; GO_REF:0000003 MODIFY
8 GO:0004674 protein serine/threonine kinase activity ISS; GO_REF:0000024 MODIFY
9 GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity IBA; GO_REF:0000033 ACCEPT
10 GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity IEA; GO_REF:0000002 ACCEPT
11 GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity IMP; PMID:25329545 ACCEPT
12 GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity ISS; GO_REF:0000024 ACCEPT
13 GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity ISS; GO_REF:0000024 ACCEPT
14 GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity ISS; PMID:10504407 ACCEPT
15 GO:0005524 ATP binding IEA; GO_REF:0000002 KEEP_AS_NON_CORE
16 GO:0005634 nucleus IBA; GO_REF:0000033 KEEP_AS_NON_CORE
17 GO:0005737 cytoplasm IBA; GO_REF:0000033 ACCEPT
18 GO:0005737 cytoplasm IEA; GO_REF:0000044 ACCEPT
19 GO:0005737 cytoplasm ISS; GO_REF:0000024 ACCEPT
20 GO:0005829 cytosol IBA; GO_REF:0000033 ACCEPT
21 GO:0006446 regulation of translational initiation ISS; GO_REF:0000024 MODIFY
22 GO:0006468 protein phosphorylation ISS; GO_REF:0000024 MODIFY
23 GO:0006468 protein phosphorylation ISS; GO_REF:0000024 MODIFY
24 GO:0007612 learning ISS; GO_REF:0000024 KEEP_AS_NON_CORE
25 GO:0007616 long-term memory ISS; GO_REF:0000024 KEEP_AS_NON_CORE
26 GO:0010998 regulation of translational initiation by eIF2 alpha phosphorylation IMP; PMID:26102367 ACCEPT
27 GO:0010998 regulation of translational initiation by eIF2 alpha phosphorylation ISS; GO_REF:0000024 ACCEPT
28 GO:0019081 viral translation ISS; GO_REF:0000024 MODIFY
29 GO:0022626 cytosolic ribosome ISS; GO_REF:0000024 KEEP_AS_NON_CORE
30 GO:0032057 negative regulation of translational initiation in response to stress IBA; GO_REF:0000033 ACCEPT
31 GO:0032057 negative regulation of translational initiation in response to stress ISS; GO_REF:0000024 ACCEPT
32 GO:0034198 cellular response to amino acid starvation IBA; GO_REF:0000033 ACCEPT
33 GO:0034198 cellular response to amino acid starvation IMP; PMID:25329545 ACCEPT
34 GO:0034644 cellular response to UV ISS; GO_REF:0000024 KEEP_AS_NON_CORE
35 GO:0044828 host-mediated suppression of viral genome replication ISS; GO_REF:0000024 KEEP_AS_NON_CORE
36 GO:0045665 negative regulation of neuron differentiation ISS; GO_REF:0000024 MODIFY
37 GO:0045947 negative regulation of translational initiation ISS; GO_REF:0000024 MODIFY
38 GO:0046777 protein autophosphorylation ISS; GO_REF:0000024 ACCEPT
39 GO:0051246 regulation of protein metabolic process IEA; GO_REF:0000117 MODIFY
40 GO:0060259 regulation of feeding behavior ISS; GO_REF:0000024 KEEP_AS_NON_CORE
41 GO:0070417 cellular response to cold IMP; PMID:25329545 UNDECIDED
42 GO:0071264 positive regulation of translational initiation in response to starvation ISS; GO_REF:0000024 ACCEPT
43 GO:0106310 protein serine kinase activity IEA; GO_REF:0000116 MODIFY
44 GO:0106310 protein serine kinase activity ISS; GO_REF:0000024 MODIFY
45 GO:0140469 GCN2-mediated signaling IDA; PMID:25329545 ACCEPT
46 GO:0140469 GCN2-mediated signaling IDA; PMID:39947182 ACCEPT
47 GO:0140469 GCN2-mediated signaling IMP; PMID:26102367 ACCEPT
48 GO:0140469 GCN2-mediated signaling ISS; GO_REF:0000024 ACCEPT
49 GO:1900273 positive regulation of long-term synaptic potentiation ISS; GO_REF:0000024 KEEP_AS_NON_CORE
50 GO:1990138 neuron projection extension ISS; GO_REF:0000024 MODIFY
51 GO:1990928 response to amino acid starvation IMP; PMID:25329545 MODIFY

The portable parser exposes the complete selected ancestral path and exact donor joins. It verifies the target sequence and literal rule conditions; it does not infer biological truth from donor counts, prediction scores or the number of references. The broad kinase EC/Rhea mappings are refined using substrate evidence, rather than treating the mappings themselves as substrate-specific assays.

The normal publication and database caches remain unedited. Source snapshot hashes, original locators and cache/access distinctions are also available in EIF2AK4-source-evidence.yaml. No publication excerpt has been added.

Claim-specific primary-source locators

These locators provide a direct route from a reviewed claim to the relevant experiment without asserting a publication quotation. Cache line numbers are one-based in the exact files identified by the hashes below. Original section and figure locators identify separately accessed material when the normal cache contains only an abstract. A figure-caption read is not an image read.

Rows / claim Original source Operative locator and scope Unchanged cache SHA-256
0: tRNA-regulatory inference PMID:16601681(https://pmc.ncbi.nlm.nih.gov/articles/PMC1440839/) Results Figure 1A; Figure 2E; Methods. Cache lines 95, 109, 167, 175. Mouse kinase/tRNA-dependent activation and HisRS controls; the direct RNA-probe assay uses viral RNA, not a purified human tRNA-binding assay. ec79a5c87b2c0751fc52eedabef05e16d97510909551c48d52fb266f72bb1312
1: unresolved human checkpoint transfer PMID:17369398(https://genesdev.cshlp.org/content/21/6/649.full.html) Selected Results; Figure 3B–D and Figure 5C. Separately indexed original text establishes fungal Gcn2 checkpoint participation. The later normal full-text cache was not counted as an additional complete body read. 3637d49d0c3778c995dfca132fc51589c0ecaca1b0d591fef98623009209ce19
1: stimulus-specific fungal checkpoint PMID:19033384(https://doi.org/10.1242/jcs.035428) Selected Results on hydrogen peroxide; Figure 2A–E. Gcn2-dependent G1/pre-RC delay is positive evidence; complete operative Methods were unavailable. Cache remains abstract-only. 3f7eaddc4e61428cd098ad68dc09d69a738edd0f8a13cda22c3a18779ea05c7b
19, 29, 36, 50: GCN2 fractionation and neuronal context PMID:23447528(https://pmc.ncbi.nlm.nih.gov/articles/PMC3624466/) Experimental Procedures: antibodies and Polysome Profiles; Figure 5C–F; accompanying Results and Discussion. External original access, separate from the abstract-only cache. GCN2 is quantified independently of IMPACT, relative to input (E) and polysomal rpS6 (F). Indexed Results have a discontinuity; complete caption is available. Neurite and NeuN results remain separately scoped; no image-pixel or supplement interpretation. 88202744c3808e2ab297bbbcd561875fbbd1f737a3e86e05ee6a97239ee3233a
3: contextual immune contribution PMID:24310610(https://pmc.ncbi.nlm.nih.gov/articles/PMC4048998/) Main Results, Figure 1D, Figure 2F/G, Figure 4A/K. Human dendritic-cell signaling is separate from mouse conditional-knockout and cross-presentation/T-cell assays. Cache includes main text but lacks Methods and separate supplements; optional review Boolean omitted. 5f38785457c349266a155d545d0f6c7b34564a05bed0e330f216afbe22da3df9
26: selective translation PMID:26102367(https://doi.org/10.1371/journal.pgen.1005212) Results Figure 1E and p21 transcript-variant reporter/polysome experiments. Cache lines 108, 128, 136, 138, 146. Human SQ20B GCN2 perturbation is separate from the mouse uORF reporter and polysome work; increased selected-transcript translation coexists with reduced bulk initiation. 7e78a9a12bb7b4098ba28d3305b4849413c3e38fc383061f52d90e56c153683f
46: GCN2 signaling PMID:39947182(https://pubmed.ncbi.nlm.nih.gov/39947182/) Results on decoding-incompetent ribosomes, GCN2 knockout and eIF2alpha phosphorylation; STAR Methods. Cache lines 128, 136, 140, 148, 244, 260, 370. Engineered human-cell rRNA/GCN2 perturbation and eIF2alpha rescue support the stress-signaling mechanism; no stable ribosome-subunit identity is inferred. de134a10c98b644d612393a45e61595e3e044be2e7c643955181394d02b0f9bf

GO:0000077 is a signaling process contributing to a DNA-damage checkpoint. Its direct is_a parents are GO:0031570 (DNA integrity checkpoint signaling) and GO:0042770 (signal transduction in response to DNA damage), verified in the current official term record. The definition does not require activation by every damaging stimulus. The positive fungal experiments support a real checkpoint role; the review's remaining uncertainty concerns its transfer to human EIF2AK4.

The review-level availability field is optional and does not encode the normal-cache acquisition flag. For PMID:23447528 and PMID:24310610 it is omitted; the explicit access accounts above supersede any inference that the first source was read only as an abstract or that every section of the second was recovered. Machine-cache flags and bytes remain unchanged. The structured evidence file carries the same access accounts.

Curated evidence and core coverage (2026-10-27)

The unchanged UniProt record is now explicitly referenced in the review. FUNCTION lines 267–268 and DOMAIN lines 332–336 support uncharged-tRNA sensing by similarity; SUBUNIT lines 304–315 distinguish by-similarity GCN1/IMPACT and DNAJC3 regulation from the PMID:32610081-supported MAP3K20 interaction. SUBCELLULAR LOCATION line 320 is a positive cytoplasmic inference, not proof of exclusive localization. PTM lines 337–339 describe activation-related autophosphorylation by similarity. The tRNA-binding and autophosphorylation statements record the same Q9QZ05-to-human transfer as the imported ISS rows, rather than independent corroboration. ECO:0000250 is not relabeled as direct human experimental evidence, and none of these statements assigns equal function to all natural products.

For row 16, the positive evidence is the literal nucleus IBD at PTN000113601, on the target lineage ending at PTN002475950. The saved PAINT projection retains that record at IBD.gaf line 44279 and all selected lineage records. A deep ancestral placement or absent target donor does not establish a loss. For row 29, the positive yeast association and mouse N2a Figure 5C–F GCN2 measurements precede the limits on direct contact and human generalization. The reviewed cold-response and checkpoint uncertainties remain unchanged.

The separate tRNA-binding core uses GO:0000049 as a molecular function, not contributes_to_molecular_function. GO:0034198 names the nutrient-response context; GO:0046777 identifies the kinase's activation-related autophosphorylation. Official typed ancestor closures, checked on 2026-10-27, contain no ancestor/descendant pair among these four core processes. GO:0004694's closure already includes GO:0010998; repeating that term would add no distinct core coverage. The tRNA-binding and eIF2alpha-kinase terms likewise have no hierarchy between them. These core changes add no annotation row or publication quotation.