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Q9Z2R9

- E2AK1_MOUSE

UniProt

Q9Z2R9 - E2AK1_MOUSE

Protein

Eukaryotic translation initiation factor 2-alpha kinase 1

Gene

Eif2ak1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 2 (05 Apr 2011)
      Previous versions | rss
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    Functioni

    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.3 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Induced by acute heme depletion, that not only increases EIF2AK1 protein levels, but also stimulates kinase activity by autophosphorylation. Inhibited by the heme-degradation products biliverdin and bilirubin. Induced by oxidative stress generated by arsenite treatment. 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.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei80 – 801Heme-bindingBy similarity
    Binding sitei196 – 1961ATPPROSITE-ProRule annotation
    Active sitei440 – 4401Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi173 – 1819ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. eukaryotic translation initiation factor 2alpha kinase activity Source: UniProtKB
    3. heme binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. protein homodimerization activity Source: UniProtKB
    6. protein kinase activity Source: MGI

    GO - Biological processi

    1. negative regulation of cell proliferation Source: UniProtKB
    2. negative regulation of hemoglobin biosynthetic process Source: UniProtKB
    3. negative regulation of translation Source: UniProtKB-KW
    4. protein autophosphorylation Source: UniProtKB
    5. protoporphyrinogen IX metabolic process Source: MGI
    6. regulation of eIF2 alpha phosphorylation by heme Source: MGI
    7. regulation of hemoglobin biosynthetic process Source: MGI
    8. regulation of translation Source: MGI
    9. response to external stimulus Source: UniProtKB
    10. response to stress Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Protein synthesis inhibitor, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eukaryotic translation initiation factor 2-alpha kinase 1 (EC:2.7.11.1)
    Alternative name(s):
    Heme-controlled repressor
    Short name:
    HCR
    Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase
    Heme-regulated inhibitor
    Hemin-sensitive initiation factor 2-alpha kinase
    Gene namesi
    Name:Eif2ak1
    Synonyms:Hri
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:1353448. Eif2ak1.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Eif2ak1 are a cause of hyperchromic anemia in animals suffering from iron deficiency. The number of red blood cells is decreased due to increased apoptosis of erythroid precursor cells, probably because globins misfold and aggregate in the absence of heme.

    Disruption phenotypei

    Mice are viable and fertile without gross morphological abnormalities. Dramatically altered response to diet-induced iron deficiency shifting from an adaptive decrease in RBC volume and intracellular hemoglobin content to an increased production of abnormally dense red blood cells (RBCs) with decreasing red cell counts. The decrease in RBC number is the result of increased apoptosis of erythroid precursors. Diminished levels of phosphorylated EIF2S1 in bone marrow-derived macrophages (BMDMs). Impaired maturation of BMDMs and blunted inflammatory response to LPS with a reduced cytokine production. Impaired phagocytosis of senescent RBCs by macrophages, resulting in a lower phagocytosis index and lower percentage of macrophages with ingested RBC. In hepatocytes, cytochromes P450 CYP2B6 and CYP3A induction by phenobarbital is not impaired in response to acute heme depletion and CYP2B6 and CYP3A proteins continue to accumulate to supranormal levels, irrespective of the hepatic heme pool status. These cells also exhibit a weak, albeit significant, elevation of the basal ER-stress as reflected by elevated levels of autophosphorylated EIF2AK3/PERK and EIF2AK4/GCN2, the ER-stress related chaperones HSPA5 and HSP90B1, and total hepatic protein ubiquitination.3 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi196 – 1961K → R: Abolishes kinase activity. 2 Publications
    Mutagenesisi483 – 4831T → A: No effect on kinase activity. 1 Publication
    Mutagenesisi483 – 4831T → D: No effect on kinase activity. 1 Publication
    Mutagenesisi485 – 4851T → A: Abolishes kinase activity. 1 Publication
    Mutagenesisi485 – 4851T → D: Constitutively active kinase; loss of regulation by heme and arsenite. 1 Publication
    Mutagenesisi490 – 4901T → A: Almost complete loss of kinase activity; even upon arsenite treatment. 1 Publication
    Mutagenesisi490 – 4901T → D: Almost complete loss of kinase activity; even upon arsenite treatment. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 619619Eukaryotic translation initiation factor 2-alpha kinase 1PRO_0000085942Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei483 – 4831Phosphothreonine; by autocatalysis1 Publication
    Modified residuei485 – 4851Phosphothreonine; by autocatalysis1 Publication
    Modified residuei490 – 4901Phosphothreonine; by autocatalysis1 Publication

    Post-translational modificationi

    Activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues. Autophosphorylation at Thr-485 is required for kinase activation. The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations.1 Publication

    Keywords - PTMi

    Disulfide bond, Phosphoprotein

    Proteomic databases

    PRIDEiQ9Z2R9.

    PTM databases

    PhosphoSiteiQ9Z2R9.

    Expressioni

    Tissue specificityi

    Expressed predominantly in erythroid cells, mature reticulocytes, as well as fetal liver nucleated erythroid cells. At much lower levels, expressed in hepatocytes and bone marrow-derived macrophages (at protein level).3 Publications

    Developmental stagei

    Highly expressed in fetal liver erythroid precursor cells at 14.5 dpc (at protein level).1 Publication

    Inductioni

    By phenobarbital.1 Publication

    Gene expression databases

    ArrayExpressiQ9Z2R9.
    BgeeiQ9Z2R9.
    GenevestigatoriQ9Z2R9.

    Interactioni

    Subunit structurei

    Synthesized in an inactive form that binds to the N-terminal domain of CDC37. Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation By similarity. Forms oligomers. Has been reported as a homodimer, as well as a hexamer in the absence of hemin. Converted to an inactive disulfide linked homodimer in the presence of hemin.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Eif2s1Q6ZWX66EBI-642878,EBI-1202234

    Protein-protein interaction databases

    BioGridi200421. 1 interaction.
    IntActiQ9Z2R9. 2 interactions.
    MINTiMINT-1746990.
    STRINGi10090.ENSMUSP00000098056.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z2R9.
    SMRiQ9Z2R9. Positions 162-235, 378-619.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini167 – 580414Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Repeati408 – 4136HRM 1
    Repeati549 – 5546HRM 2

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00530000062984.
    HOVERGENiHBG051429.
    InParanoidiQ69ZK8.
    KOiK16194.
    OMAiNADWTNR.
    OrthoDBiEOG70GMF6.
    PhylomeDBiQ9Z2R9.
    TreeFamiTF329383.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 2 hits.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 2 hits.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Z2R9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLGGSSVDGE RDTDDDAAGA VAAPPAIDFP AEVSDPKYDE SDVPAELQVL    50
    KEPLQQPTFP FLVANQLLLV SLLEHLSHVH EPNPLHSKQV FKLLCQTFIK 100
    MGLLSSFTCS DEFSSLRLHH NRAITHLMRS AKERVRQDPC QDNSYMQKIR 150
    SREIAFEAQT SRYLNEFEEL AILGKGGYGR VYKVRNKLDG QHYAIKKILI 200
    KSATKTDCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVV QPQDRVPIQL 250
    PSLEVLSEQE GDRDQGGVKD NESSSSIVFA ELTPEKEKPF GESEVKNENN 300
    NLVSYTANLV VRNSSESESS IELQEDGLTD LSVRPVVRHQ LPLGHSSELE 350
    GNFTSTDESS EGNLNLLGQT EVRYHLMLHI QMQLCELSLW DWITERNKRS 400
    REYVDEAACP YVMASVATKI FQELVEGVFY IHNMGIVHRD LKPRNIFLHG 450
    PDQQVKIGDF GLACADIIQN ADWTNRNGKG TRTHTSRVGT CLYASPEQLE 500
    GSQYDAKSDM YSLGVILLEL FQPFGTEMER ATVLTGVRTG RIPESLSKRC 550
    PVQAKYIQLL TGRNVSQRPS ALQLLQSELF QTTGNVNLTL QMKIIEQEKE 600
    IEELKKQLSL LSQDRGLKR 619
    Length:619
    Mass (Da):69,702
    Last modified:April 5, 2011 - v2
    Checksum:i39DC5FF950C92F2A
    GO

    Sequence cautioni

    The sequence BAD32438.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti20 – 201A → S in BAB32242. (PubMed:16141072)Curated
    Sequence conflicti71 – 711S → C in BAB32242. (PubMed:16141072)Curated
    Sequence conflicti138 – 15013DPCQD…MQKIR → VSPTGCTLYDKYI in BAB32242. (PubMed:16141072)CuratedAdd
    BLAST
    Sequence conflicti196 – 1972KK → IE in BAB29545. (PubMed:16141072)Curated
    Sequence conflicti371 – 3711E → D in AAC79201. (PubMed:9822714)Curated
    Sequence conflicti371 – 3711E → D in AAK55766. (PubMed:11726526)Curated
    Sequence conflicti565 – 5651V → A in AAH28923. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF028808 mRNA. Translation: AAC79201.1.
    AY033898 mRNA. Translation: AAK55766.1.
    AK173160 mRNA. Translation: BAD32438.1. Different initiation.
    BC028923 mRNA. Translation: AAH28923.1.
    BC111035 mRNA. Translation: AAI11036.1.
    AK014775 mRNA. Translation: BAB29545.1.
    AK020887 mRNA. Translation: BAB32242.1.
    AK032508 mRNA. Translation: BAC27901.1.
    RefSeqiNP_038585.2. NM_013557.2.
    UniGeneiMm.389709.
    Mm.431968.

    Genome annotation databases

    EnsembliENSMUST00000100487; ENSMUSP00000098056; ENSMUSG00000029613.
    GeneIDi15467.
    KEGGimmu:15467.
    UCSCiuc029vqe.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF028808 mRNA. Translation: AAC79201.1 .
    AY033898 mRNA. Translation: AAK55766.1 .
    AK173160 mRNA. Translation: BAD32438.1 . Different initiation.
    BC028923 mRNA. Translation: AAH28923.1 .
    BC111035 mRNA. Translation: AAI11036.1 .
    AK014775 mRNA. Translation: BAB29545.1 .
    AK020887 mRNA. Translation: BAB32242.1 .
    AK032508 mRNA. Translation: BAC27901.1 .
    RefSeqi NP_038585.2. NM_013557.2.
    UniGenei Mm.389709.
    Mm.431968.

    3D structure databases

    ProteinModelPortali Q9Z2R9.
    SMRi Q9Z2R9. Positions 162-235, 378-619.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200421. 1 interaction.
    IntActi Q9Z2R9. 2 interactions.
    MINTi MINT-1746990.
    STRINGi 10090.ENSMUSP00000098056.

    Chemistry

    ChEMBLi CHEMBL1938213.

    PTM databases

    PhosphoSitei Q9Z2R9.

    Proteomic databases

    PRIDEi Q9Z2R9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000100487 ; ENSMUSP00000098056 ; ENSMUSG00000029613 .
    GeneIDi 15467.
    KEGGi mmu:15467.
    UCSCi uc029vqe.1. mouse.

    Organism-specific databases

    CTDi 27102.
    MGIi MGI:1353448. Eif2ak1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00530000062984.
    HOVERGENi HBG051429.
    InParanoidi Q69ZK8.
    KOi K16194.
    OMAi NADWTNR.
    OrthoDBi EOG70GMF6.
    PhylomeDBi Q9Z2R9.
    TreeFami TF329383.

    Miscellaneous databases

    ChiTaRSi EIF2AK1. mouse.
    NextBioi 288300.
    PROi Q9Z2R9.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Z2R9.
    Bgeei Q9Z2R9.
    Genevestigatori Q9Z2R9.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 2 hits.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 2 hits.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of the hemin-sensitive eukaryotic initiation factor 2alpha kinase from mouse nonerythroid cells."
      Berlanga J.J., Herrero S., de Haro C.
      J. Biol. Chem. 273:32340-32346(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-196, AUTOPHOSPHORYLATION.
      Strain: C57BL/6 X CBA.
      Tissue: Liver.
    2. "Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency."
      Han A.-P., Yu C., Lu L., Fujiwara Y., Browne C., Chin G., Fleming M., Leboulch P., Orkin S.H., Chen J.-J.
      EMBO J. 20:6909-6918(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE.
      Tissue: Erythroleukemia.
    3. "Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
      Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
      DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Pancreatic islet.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J and FVB/N.
      Tissue: Eye and Salivary gland.
    5. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-211 AND 445-619.
      Strain: C57BL/6J.
      Tissue: Head, Olfactory bulb and Retina.
    6. "Multiple autophosphorylation is essential for the formation of the active and stable homodimer of heme-regulated eIF2alpha kinase."
      Bauer B.N., Rafie-Kolpin M., Lu L., Han A., Chen J.-J.
      Biochemistry 40:11543-11551(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOPHOSPHORYLATION, HEME-BINDING.
    7. "Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses."
      Lu L., Han A.P., Chen J.J.
      Mol. Cell. Biol. 21:7971-7980(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION BY HEME DEFICIENCY; HEAT SHOCK; OSMOTIC STRESS AND OXIDATIVE STRESS, TISSUE SPECIFICITY.
    8. "Autophosphorylation of threonine 485 in the activation loop is essential for attaining eIF2alpha kinase activity of HRI."
      Rafie-Kolpin M., Han A.P., Chen J.J.
      Biochemistry 42:6536-6544(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-483; THR-485 AND THR-490, ENZYME REGULATION, MUTAGENESIS OF LYS-196; THR-483; THR-485 AND THR-490.
    9. "Activation of heme-regulated eukaryotic initiation factor 2alpha kinase by nitric oxide is induced by the formation of a five-coordinate NO-heme complex: optical absorption, electron spin resonance, and resonance raman spectral studies."
      Igarashi J., Sato A., Kitagawa T., Yoshimura T., Yamauchi S., Sagami I., Shimizu T.
      J. Biol. Chem. 279:15752-15762(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: HEME-BINDING, ENZYME REGULATION.
    10. "Characterization of heme-regulated eIF2alpha kinase: roles of the N-terminal domain in the oligomeric state, heme binding, catalysis, and inhibition."
      Miksanova M., Igarashi J., Minami M., Sagami I., Yamauchi S., Kurokawa H., Shimizu T.
      Biochemistry 45:9894-9905(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, OLIGOMERIZATION, HEME-BINDING, INDUCTION.
    11. "The function of heme-regulated eIF2alpha kinase in murine iron homeostasis and macrophage maturation."
      Liu S., Suragani R.N., Wang F., Han A., Zhao W., Andrews N.C., Chen J.J.
      J. Clin. Invest. 117:3296-3305(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
    12. "Hepatic heme-regulated inhibitor (HRI) eukaryotic initiation factor 2alpha kinase: a protagonist of heme-mediated translational control of CYP2B enzymes and a modulator of basal endoplasmic reticulum stress tone."
      Acharya P., Chen J.J., Correia M.A.
      Mol. Pharmacol. 77:575-592(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, ENZYME REGULATION, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiE2AK1_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z2R9
    Secondary accession number(s): Q2TA96
    , Q69ZK8, Q8C024, Q8K123, Q9CTP5, Q9D601
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: April 5, 2011
    Last modified: October 1, 2014
    This is version 130 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3