Rabbit anti-Human HRI (EIF2AK1) Polyclonal Antibody | anti-EIF2AK1 antibody

HRI (EIF2AK1) Antibody (Center)

Cat. Num. AAA9206335

• Gene Names: EIF2AK1; HCR; HRI
• Reactivity: Human
• Applications: Western Blot, ELISA, Immunohistochemistry
• Purity: Purified Rabbit Polyclonal Antibody (Pab)
• Synonyms: HRI (EIF2AK1); Polyclonal Antibody; HRI (EIF2AK1) Antibody (Center); HRI; KIAA1369; anti-EIF2AK1 antibody

• Host: Rabbit
• Reactivity: Human
• Clonality: Polyclonal
• Isotype: Rabbit Ig
• Specificity: This HRI (EIF2AK1) antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 267-296 amino acids from the Central region of human HRI (EIF2AK1).
• Purity/Purification: Purified Rabbit Polyclonal Antibody (Pab)
• Form/Format: Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is prepared by Saturated Ammonium Sulfate (SAS) precipitation followed by dialysis against PBS.
• Sequence Positions: 267-296
• Sequence Length: 629

• Applicable Applications for anti-EIF2AK1 antibody: Western Blot (WB), ELISA (EIA), Immunohistochemistry - Paraffin (IHC-P)
• Application Notes: WB~~1:1000; IHC-P~~1:10~50
• Function: Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser- 48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions (By similarity).
• Cellular Location: Cytoplasm.
• Tissue Location: Expressed predominantly in erythroid cells. At much lower levels, expressed in hepatocytes (at protein level)
• Function: 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).
• Preparation and Storage: Maintain refrigerated at 2-8 degree C for up to 2 weeks. For long term storage store at -20 degree C in small aliquots to prevent freeze-thaw cycles.

Western Blot (WB)

(Western blot analysis of EIF2AK1 Antibody (Center) in Hela cell line lysates (35ug/lane). EIF2AK1 (arrow) was detected using the purified Pab.)

Immunohistochemistry (IHC)

(Formalin-fixed and paraffin-embedded human lung carcinoma tissue reacted with EIF2AK1 antibody (Center), which was peroxidase-conjugated to the secondary antibody, followed by DAB staining. This data demonstrates the use of this antibody for immunohistochemistry; clinical relevance has not been evaluated.)

Related Product Information for anti-EIF2AK1 antibody

The HRI gene is localized to 7p22 where its 3' end slightly overlaps the 3' end of the gene JTV1. The two genes are transcribed from opposite strands. Studies in rat and rabbit suggest that the HRI gene product phosphorylates the alpha subunit of eukaryotic initiation factor 2. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme.

Product Categories/Family for anti-EIF2AK1 antibody

Signal Transduction

References

Hwang S.-Y., Mol. Cells 10:584-591(2000).
Omasa T., DNA Seq. 13:133-137(2002).

NCBI and Uniprot Product Information

• NCBI GI #: 197245437
• NCBI GeneID: 27102
• NCBI Accession #: NP_001127807.1; NP_055228.2
• NCBI GenBank Nucleotide #: NM_001134335.1
• UniProt Accession #: Q9BQI3; Q549K6; Q8NBW3; Q9HC02; Q9NYE0; Q9P0V6; Q9P1J5; Q9P2H8; Q9UHG4; A8K2R2
• Molecular Weight: 71106
• NCBI Official Full Name: eukaryotic translation initiation factor 2-alpha kinase 1 isoform b
• NCBI Official Synonym Full Names: eukaryotic translation initiation factor 2-alpha kinase 1
• NCBI Official Symbol: EIF2AK1
• NCBI Official Synonym Symbols: HCR; HRI
• NCBI Protein Information: eukaryotic translation initiation factor 2-alpha kinase 1
• UniProt Protein Name: Eukaryotic translation initiation factor 2-alpha kinase 1
• Protein Family: Eukaryotic translation initiation factor 2-alpha kinase
• UniProt Gene Name: EIF2AK1
• UniProt Synonym Gene Names: HRI; KIAA1369; HCR
• UniProt Entry Name: E2AK1_HUMAN

NCBI Description

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. [provided by RefSeq, Aug 2008]

Uniprot Description

HRI: a protein kinase of the PEK family. Phosphorylates the alpha subunit of eukaryotic initiation factor 2 in response to various stress conditions, inhibiting protein synthesis at the level of initiation. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity. Requires association with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosporylation. Two alternatively spliced isoforms have been described.

Protein type: Kinase, protein; Protein kinase, Other; Translation; Protein kinase, Ser/Thr (non-receptor); EC 2.7.11.1; Other group; PEK family

Chromosomal Location of Human Ortholog: 7p22

Cellular Component: cytoplasm

Molecular Function: protein homodimerization activity; heme binding; ATP binding; eukaryotic translation initiation factor 2alpha kinase activity

Biological Process: response to external stimulus; negative regulation of cell proliferation; negative regulation of translational initiation by iron; protoporphyrinogen IX metabolic process; protein amino acid autophosphorylation; response to stress; negative regulation of hemoglobin biosynthetic process