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Rabbit Anti-EIF2AK1 (AA 271-630) Recombinant Antibody (7H3L3) (CBMAB-H1004-FY)

This product is rabbit antibody that recognizes EIF2AK1. The antibody 7H3L3 can be used for immunoassay techniques such as: WB.
See all EIF2AK1 antibodies

Summary

Host Animal
Rabbit
Specificity
Human
Clone
7H3L3
Antibody Isotype
IgG
Application
WB

Basic Information

Immunogen
Protein corresponding to human elF2AK1/Heme regulated inhibitor
Specificity
Human
Antibody Isotype
IgG
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
PBS, pH 7.4
Preservative
0.09% Sodium azide
Concentration
0.5 mg/mL
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Epitope
AA 271-630

Target

Full Name
Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1
Introduction
The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene.
Entrez Gene ID
27102
UniProt ID
Q9BQI3
Alternative Names
Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1; Heme-Regulated Eukaryotic Initiation Factor EIF-2-Alpha Kinase; Hemin-Sensitive Initiation Factor 2-Alpha Kinase; Heme Regulated Initiation Factor 2 Alpha Kinase; Heme-Controlled Repressor; Heme-Regulated Inhibitor; EC 2.7.11.1; HCR
Research Area
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707).

Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707).

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, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707).

Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity).

This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity).

Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity).

In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity).

It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity).

Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (By similarity).

May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (By similarity).

Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707).
Biological Process
Acute inflammatory response Source: Ensembl
HRI-mediated signaling Source: UniProtKB
Integrated stress response signaling Source: UniProtKB
Iron ion homeostasis Source: Ensembl
Macrophage differentiation Source: Ensembl
Negative regulation of cell population proliferation Source: Ensembl
Negative regulation of hemoglobin biosynthetic process Source: UniProtKB
Negative regulation of translational initiation by iron Source: UniProtKB
Phagocytosis Source: Ensembl
Protein autophosphorylation Source: UniProtKB
Protoporphyrinogen IX metabolic process Source: Ensembl
Regulation of eIF2 alpha phosphorylation by heme Source: Ensembl
Response to iron ion starvation Source: UniProtKB
Cellular Location
Cytoplasm
Involvement in disease
Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome (LEMSPAD):
A disorder characterized by delayed motor development, speech delay with dysarthria, hypertonia, progressive spasticity, hyperreflexia, and bradykinesia. Cognition is normal. Patients manifest anxiety and attention deficit-hyperactivity disorder.
PTM
Activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues. Autophosphorylation at Thr-488 is required for kinase activation. The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations.
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For research use only. Not intended for any clinical use.

Custom Antibody Labeling

We also offer labeled antibodies developed using our catalog antibody products and nonfluorescent conjugates (HRP, AP, Biotin, etc.) or fluorescent conjugates (Alexa Fluor, FITC, TRITC, Rhodamine, Texas Red, R-PE, APC, Qdot Probes, Pacific Dyes, etc.).

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