Eukaryotic translation initiation factor 2-alpha kinase 1

Details

Name

Eukaryotic translation initiation factor 2-alpha kinase 1

Synonyms

• 2.7.11.1
• HCR
• Heme-controlled repressor
• Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase
• Heme-regulated inhibitor
• Hemin-sensitive initiation factor 2-alpha kinase
• HRI
• KIAA1369

Gene Name

EIF2AK1

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051744|Eukaryotic translation initiation factor 2-alpha kinase 1
MQGGNSGVRKREEEGDGAGAVAAPPAIDFPAEGPDPEYDESDVPAEIQVLKEPLQQPTFP
FAVANQLLLVSLLEHLSHVHEPNPLRSRQVFKLLCQTFIKMGLLSSFTCSDEFSSLRLHH
NRAITHLMRSAKERVRQDPCEDISRIQKIRSREVALEAQTSRYLNEFEELAILGKGGYGR
VYKVRNKLDGQYYAIKKILIKGATKTVCMKVLREVKVLAGLQHPNIVGYHTAWIEHVHVI
QPRADRAAIELPSLEVLSDQEEDREQCGVKNDESSSSSIIFAEPTPEKEKRFGESDTENQ
NNKSVKYTTNLVIRESGELESTLELQENGLAGLSASSIVEQQLPLRRNSHLEESFTSTEE
SSEENVNFLGQTEAQYHLMLHIQMQLCELSLWDWIVERNKRGREYVDESACPYVMANVAT
KIFQELVEGVFYIHNMGIVHRDLKPRNIFLHGPDQQVKIGDFGLACTDILQKNTDWTNRN
GKRTPTHTSRVGTCLYASPEQLEGSEYDAKSDMYSLGVVLLELFQPFGTEMERAEVLTGL
RTGQLPESLRKRCPVQAKYIQHLTRRNSSQRPSAIQLLQSELFQNSGNVNLTLQMKIIEQ
EKEIAELKKQLNLLSQDKGVRDDGKDGGVG

Number of residues

630

Molecular Weight

71105.915

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / eukaryotic translation initiation factor 2alpha kinase activity / heme binding / protein homodimerization activity

Processes

acute inflammatory response / iron ion homeostasis / macrophage differentiation / negative regulation of cell proliferation / negative regulation of hemoglobin biosynthetic process / negative regulation of translational initiation by iron / phagocytosis / protein autophosphorylation / protoporphyrinogen IX metabolic process / regulation of eIF2 alpha phosphorylation by heme / response to iron ion starvation

Components

cytoplasm

General 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).

Specific Function

Atp binding

Pfam Domain Function

• Pkinase (PF00069)

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm

Gene sequence

>lcl|BSEQ0051745|Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)
ATGCAGGGGGGCAACTCCGGGGTCCGCAAGCGCGAAGAGGAGGGCGACGGGGCTGGGGCT
GTGGCTGCGCCGCCGGCCATCGACTTTCCCGCCGAGGGCCCGGACCCCGAATATGACGAA
TCTGATGTTCCAGCAGAAATCCAGGTGTTAAAAGAACCCCTACAACAGCCAACCTTCCCT
TTTGCAGTTGCAAACCAACTCTTGCTGGTTTCTTTGCTGGAGCACTTGAGCCACGTGCAT
GAACCAAACCCACTTCGTTCAAGACAGGTGTTTAAGCTACTTTGCCAGACGTTTATCAAA
ATGGGGCTGCTGTCTTCTTTCACTTGTAGTGACGAGTTTAGCTCATTGAGACTACATCAC
AACAGAGCTATTACTCACTTAATGAGGTCTGCTAAAGAGAGAGTTCGTCAGGATCCTTGT
GAGGATATTTCTCGTATCCAGAAAATCAGATCAAGGGAAGTAGCCTTGGAAGCACAAACT
TCACGTTACTTAAATGAATTTGAAGAACTTGCCATCTTAGGAAAAGGTGGATACGGAAGA
GTATACAAGGTCAGGAATAAATTAGATGGTCAGTATTATGCAATAAAAAAAATCCTGATT
AAGGGTGCAACTAAAACAGTTTGCATGAAGGTCCTACGGGAAGTGAAGGTGCTGGCAGGT
CTTCAGCACCCCAATATTGTTGGCTATCACACCGCGTGGATAGAACATGTTCATGTGATT
CAGCCACGAGCAGACAGAGCTGCCATTGAGTTGCCATCTCTGGAAGTGCTCTCCGACCAG
GAAGAGGACAGAGAGCAATGTGGTGTTAAAAATGATGAAAGTAGCAGCTCATCCATTATC
TTTGCTGAGCCCACCCCAGAAAAAGAAAAACGCTTTGGAGAATCTGACACTGAAAATCAG
AATAACAAGTCGGTGAAGTACACCACCAATTTAGTCATAAGAGAATCTGGTGAACTTGAG
TCGACCCTGGAGCTCCAGGAAAATGGCTTGGCTGGTTTGTCTGCCAGTTCAATTGTGGAA
CAGCAGCTGCCACTCAGGCGTAATTCCCACCTAGAGGAGAGTTTCACATCCACCGAAGAA
TCTTCCGAAGAAAATGTCAACTTTTTGGGTCAGACAGAGGCACAGTACCACCTGATGCTG
CACATCCAGATGCAGCTGTGTGAGCTCTCGCTGTGGGATTGGATAGTCGAGAGAAACAAG
CGGGGCCGGGAGTATGTGGACGAGTCTGCCTGTCCTTATGTTATGGCCAATGTTGCAACA
AAAATTTTTCAAGAATTGGTAGAAGGTGTGTTTTACATACATAACATGGGAATTGTGCAC
CGAGATCTGAAGCCAAGAAATATTTTTCTTCATGGCCCTGATCAGCAAGTAAAAATAGGA
GACTTTGGTCTGGCCTGCACAGACATCCTACAGAAGAACACAGACTGGACCAACAGAAAC
GGGAAGAGAACACCAACACATACGTCCAGAGTGGGTACTTGTCTGTACGCTTCACCCGAA
CAGTTGGAAGGATCTGAGTATGATGCCAAGTCAGATATGTACAGCTTGGGTGTGGTCCTG
CTAGAGCTCTTTCAGCCGTTTGGAACAGAAATGGAGCGAGCAGAAGTTCTAACAGGTTTA
AGAACTGGTCAGTTGCCGGAATCCCTCCGTAAAAGGTGTCCAGTGCAAGCCAAGTATATC
CAGCACTTAACGAGAAGGAACTCATCGCAGAGACCATCTGCCATTCAGCTGCTGCAGAGT
GAACTTTTCCAAAATTCTGGAAATGTTAACCTCACCCTACAGATGAAGATAATAGAGCAA
GAAAAAGAAATTGCAGAACTAAAGAAGCAGCTAAACCTCCTTTCTCAAGACAAAGGGGTG
AGGGATGACGGAAAGGATGGGGGCGTGGGATGA

Chromosome Location

7

Locus

7p22.1

External Identifiers

Resource	Link
UniProtKB ID	Q9BQI3
UniProtKB Entry Name	E2AK1_HUMAN
HGNC ID	HGNC:24921

General References

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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details