Product Details

Uniprot No.

Target Names

Alternative Names

eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein), EIF2AK4, GCN2 KIAA1338

Species Reactivity

Human

Immunogen

A synthesized peptide from human EIF2AK4 protein

Immunogen Species

Homo sapiens (Human)

Conjugate

Non-conjugated

Clonality

Monoclonal

Isotype

Rabbit IgG

Clone No.

7G4

Purification Method

Affinity-chromatography

Concentration

It differs from different batches. Please contact us to confirm it.

Buffer

Rabbit IgG in 10mM phosphate buffered saline , pH 7.4, 150mM sodium chloride, 0.05% BSA, 0.02% sodium azide and 50% glycerol.

Form

Liquid

Tested Applications

ELISA, WB, IHC, IF, FC

Recommended Dilution

Application	Recommended Dilution
WB	1:500-1:2000
IHC	1:50-1:200
IF	1:50-1:200
FC	1:50-1:200

Protocols

ELISA Protocol
Western Blotting(WB) Protocol
Immunohistochemistry (IHC) Protocol
Immunofluorescence (IF) Protocol
Flow Cytometry (FC) Protocol

Troubleshooting and FAQs

Antibody FAQs

Storage

Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.

Lead Time

Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

Description

EIF2AK4, also known as GCN2, is a serine/threonine kinase that plays a central role in the integrated stress response by phosphorylating eukaryotic translation initiation factor 2 alpha. This kinase serves as a critical sensor of amino acid deprivation and other cellular stresses, making it an essential target for researchers investigating metabolic adaptation, autophagy regulation, and stress-induced translational control. Its involvement in tumor cell survival under nutrient-limiting conditions has also positioned GCN2 as a subject of growing interest in cancer biology.

This recombinant monoclonal antibody, generated in rabbit and derived from clone 7G4, offers the reproducibility and sequence-defined consistency that demanding experimental workflows require. Unlike traditional hybridoma-derived antibodies, recombinant production ensures lot-to-lot uniformity, allowing researchers to confidently compare results across extended studies without concerns about antibody variability.

Validation data demonstrates robust performance across multiple applications. Western blot analysis detects GCN2 in Jurkat and HEK293T whole cell lysates, with an observed band at approximately 200 kDa—slightly higher than the predicted 187 kDa molecular weight, likely reflecting post-translational modifications such as glycosylation or phosphorylation common to this kinase. Immunohistochemistry has been validated in human melanoma cancer and lymph node tissue sections using citrate buffer antigen retrieval, while immunofluorescence staining successfully localizes the protein in PC-3 cells. Flow cytometry analysis confirms detection in A431 cells with clear separation from isotype controls.

This antibody supports researchers exploring stress response pathways, translational regulation, and cancer metabolism, providing a reliable tool for characterizing GCN2 expression and localization across diverse experimental systems.

Usage

For Research Use Only. Not for use in diagnostic or therapeutic procedures.

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Target Background

Function

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability. Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Binds uncharged tRNAs. Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation. Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory. Plays a role in neurite outgrowth inhibition. Plays a proapoptotic role in response to glucose deprivation. Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways. Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication.; (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation.

Gene References into Functions

Heritable pulmonary arterial hypertension is an autosomal dominant disease characterized by reduced penetrance, variable expressivity, and female predominance. Biallelic germline mutations in the gene EIF2AK4 are now associated with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. [review] PMID: 29032562
GCN2 level was closely associateed with PRCC clinical parameters, larger tumor size, higher TNM stage, higher Fuhurman Grade, and lymph node metastasis. GCN2 overexpression is a prognostic biomarker linked to decreased OS and PFS of PRCC patients. PMID: 29865032
basal ASNS expression at protein levels was significantly correlated with sensitivity to combined treatment. These results provide mechanistic insights into the role of GCN2 in the amino acid response and a rationale for further investigation of GCN2 inhibitors for the treatment of cancer. PMID: 30061420
The biallelic founder mutation in EIF2AK4 was found in all affected cases and 2 unaffected relatives. Family screening showed 34.2% of healthy heterozygotes, high consanguinity, young age at childbirth, and frequent multiparity. Prognosis was bleak, with significant differences depending on tolerance to PVD. PMID: 28697925
Heritable Pulmonary Veno-occlusive Disease and/or Pulmonary Capillary Hemangiomatosis is an autosomal recessive disease because of biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene. PMID: 28661905
EIF2AK4 mutations can also contribute to autosomal dominantly inherited pulmonary arterial hypertension. PMID: 27809840
Heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis due to bi-allelic EIF2AK4 mutations is characterised by a younger age at diagnosis but these patients display similar disease severity compared with mutation non-carriers. Response to therapy approved for pulmonary arterial hypertension in pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis is rare. PMID: 28087362
Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable pulmonary arterial hypertension. PMID: 28972005
Data show that siRNA-mediated depletion of general control nonderepressible 2 (GCN2) increases small RNA transcripts such as tRNA and 5S rRNA, and induces the p53 pathway activation. PMID: 28189689
in response to vemurafenib, BRAF-mutated melanoma and colorectal cancer cells rapidly induced the ISR as a cytoprotective mechanism through activation of general control nonderepressible 2 (GCN2), an eIF2alpha kinase sensing amino acid levels PMID: 27965097
A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. PMID: 28012804
A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. PMID: 27884767
This is the first reported case of EIF2AK4 mutation in PVOD in a Chinese patient population. We found the frameshift EIF2AK4 mutation c.1392delT (p.Arg465fs) in this case. PMID: 27684876
IDO, through GCN2 kinase activation, downregulates the levels of TCRcomplex tchain and cMyc, resulting in the suppression of Tcell proliferation and a reduction in the levels of LDHA and GLS2 PMID: 26647830
EIF2AK4 mutation was associated with pulmonary veno-occlusive disease. PVOD patients who were not significantly exposed to trichloroethylene were more likely to harbour EIF2AK4 mutations. PMID: 26541523
Data show that sequenced eukaryotic translation initiation factor 2 alpha kinase 4 protein (EIF2AK4) with a homozygous mutation in all five families: c.3344C>T(p.P1115L). PMID: 25512148
Targeting ALDH18A1 activated the serine/threonine protein kinase GCN2 (general control nonderepressible 2) to inhibit protein synthesis in melanoma. PMID: 26082174
Upon deprivation of various amino acids, activated GCN2 up-regulates ATF4 to induce expression of the stress response protein Sestrin2, which is required to sustain repression of mTORC1 by blocking its lysosomal localization PMID: 26543160
IDO through GCN2 kinase activation inhibits CD4(+) T-cell proliferation and down-regulates key enzymes that directly or indirectly promote FA synthesis, a prerequisite for CD4(+) T-cell proliferation and differentiation into effector cell lineages. PMID: 26147366
GCN2 can exert its proapoptotic function in cancer cell death by posttranslational mechanisms. PMID: 25589675
GCN2 activation and phosphorylation of eIF2alpha in response to mTORC1 inhibition are necessary for autophagy. PMID: 25759478
This study is the first to examine the perceptual response to CPET in patients with PVOD who were carriers of EIF2AK4 mutations compared with PAH patients matched for resting haemodynamics and pulmonary function PMID: 25142489
p58IPK is a general inhibitor of the eIF2alpha kinases in that it also interacts with GCN2. Thus forced overexpression of cytoplasmic p58 delays eIF2alpha phosphorylation, suppresses GCN2 phosphorylation and prolongs protein synthesis PMID: 25329545
REVIEW: roles of GCN2 PMID: 24256275
Association of EIF2AKE with body mass index in Chinese has been confirmed and is suggested to be 'ethnic specific'. PMID: 24827717
Mutations in EIF2AK4 are likely to cause autosomal-recessive pulmonary capillary hemangiomatosis in familial and some nonfamilial cases. PMID: 24135949
EIF2AK4 mutations cause pulmonary veno-occlusive disease. PMID: 24292273
Data indicate that suppressing GCN2 and activating transcription factor 4 (ATF4), expression decreased Amino acid deprivation (AAD)-induced VEGF expression. PMID: 23908598
GCN2 has a role as an early mediator in the cellular response to HIV-1 infection PMID: 23417324
GCN2 leading to inhibition of viral RNA translation, and that HIV-1 protease cleaves GCN2 to overcome its antiviral effect. PMID: 23110064
In this review, GCN2 senses the absence of one or more amino acids by virtue of direct binding to cognate tRNAs. PMID: 23216249
The activation of autophagy in response to interferon (IFN)-gamma is promoted by tryptophan depletion and relies, at least in part, on the activation of GCN2-eIF2alpha kinase in kidney epithelial cells. PMID: 22896630
Changes in translational control of mitochondrial proteins are signaled by the activation of AMPK (AMP-activated protein kinase) and GCN2, leading also to the activation of autophagy. PMID: 22435535
The results suggest that GCN2 pathways can mediate the limiting effects of Gln deprivation on protein synthesis according to its severity. PMID: 21113813
the GCN2/eIF2alpha/ATF4 pathway is essential for the induction of the TRB3 gene transcription PMID: 21203563
Data show that impairment of autophagy stimulates PS1 expression and gamma-secretase activity through GCN2. PMID: 20168091
The authors conclude that the GCN2-eIF2alpha-ATF4 pathway is critical for maintaining metabolic homeostasis in tumour cells, making it a novel and attractive target for anti-tumour approaches. PMID: 20473272
GCN2 and its downstream target, the transcriptional activator ATF4, is critical for proliferation and survival of tumour cells after starvation for amino acids or glucose and is essential for growth in vivo in a xenograft model. PMID: 20551969
MEK functions to enhance GCN2-dependent eIF2alpha phosphorylation rather than suppressing dephosphorylation PMID: 18287093
UV-induced eIF2alpha phosphorylation by activation of both PERK and GCN2 via oxidative stress and l-arginine starvation signaling pathways. PMID: 19586904

Hide All

Involvement in disease

Pulmonary venoocclusive disease 2, autosomal recessive (PVOD2)

Subcellular Location

Cytoplasm.

Protein Families

Protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily

Tissue Specificity

Widely expressed. Expressed in lung, smooth muscle cells and macrophages.

Database Links

HGNC: 19687

OMIM: 234810

KEGG: hsa:440275

STRING: 9606.ENSP00000263791

UniGene: Hs.656673

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Code	CSB-RA584416A0HU
Size	US$210
	Order now
Image	Western Blot Positive WB detected in: Jurkat whole cell lysate(30µg), HEK293T whole cell lysate(30µg) All lanes: GCN2 antibody at 1:1000 Secondary Goat polyclonal to rabbit IgG at 1/40000 dilution Predicted band size: 187 kDa Observed band size: 200 kDa Exposure time：3min IHC image of CSB-RA584416A0HU diluted at 1:100 and staining in paraffin-embedded human melanoma cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a Goat anti-rabbit polymer IgG labeled by HRP and visualized using 0.05% DAB. IHC image of CSB-RA584416A0HU diluted at 1:100 and staining in paraffin-embedded human lymph node tissue performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a Goat anti-rabbit polymer IgG labeled by HRP and visualized using 0.05% DAB. Immunofluorescence staining of PC-3 cell with CSB-RA584416A0HU at 1:50, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeabilized using 0.2% Triton X-100 and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4°C. The secondary antibody was Alexa Fluor 488-congugated AffiniPure Goat Anti-Rabbit IgG(H+L). Overlay Peak curve showing A431 cells stained with CSB-RA584416A0HU (red line) at 1:100. The cells were fixed in 4% formaldehyde and permeated by 0.2% TritonX-100 for 10min. Then 10% normal goat serum to block non-specific protein-protein interactions followed by the antibody (1ug/110⁶cells) for 45min at 4℃. The secondary antibody used was FITC-conjugated goat anti-rabbit IgG (H+L) at 1/200 dilution for 35min at 4℃.Control antibody (green line) was Rabbit IgG (1ug/110⁶cells) used under the same conditions. Acquisition of >10,000 events was performed.
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EIF2AK4 Recombinant Monoclonal Antibody

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