EKS-MUM-00375

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00375

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
Other/PEK	362.1	5.3E-108	167	580	414

Status

Reviewed

Ensembl Protein

ENSMUSP00000098056

UniProt Accession

Q9Z2R9; Q2TA96; Q69ZK8; Q8C024; Q8K123; Q9CTP5; Q9D601;

Protein Name

Eukaryotic translation initiation factor 2-alpha kinase 1

Protein Synonyms/Alias

Heme-controlled repressor; HCR; Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase; Heme-regulated inhibitor; Hemin-sensitive initiation factor 2-alpha kinase;

Gene Name

Eif2ak1

Gene Synonyms/Alias

Eif2ak1; Hri;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000029613	ENSMUSP00000098056	ENSMUST00000100487

Organism

Mus musculus

Functional Description

Inhibits protein synthesis at the translation initiationlevel, 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.

Protein Length

619

Protein Sequence
(FASTA)

MLGGSSVDGE RDTDDDAAGA VAAPPAIDFP AEVSDPKYDE SDVPAELQVL KEPLQQPTFP 60

FLVANQLLLV SLLEHLSHVH EPNPLHSKQV FKLLCQTFIK MGLLSSFTCS DEFSSLRLHH 120

NRAITHLMRS AKERVRQDPC QDNSYMQKIR SREIAFEAQT SRYLNEFEEL AILGKGGYGR 180

VYKVRNKLDG QHYAIKKILI KSATKTDCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVV 240

QPQDRVPIQL PSLEVLSEQE GDRDQGGVKD NESSSSIVFA ELTPEKEKPF GESEVKNENN 300

NLVSYTANLV VRNSSESESS IELQEDGLTD LSVRPVVRHQ LPLGHSSELE GNFTSTDESS 360

EGNLNLLGQT EVRYHLMLHI QMQLCELSLW DWITERNKRS REYVDEAACP YVMASVATKI 420

FQELVEGVFY IHNMGIVHRD LKPRNIFLHG PDQQVKIGDF GLACADIIQN ADWTNRNGKG 480

TRTHTSRVGT CLYASPEQLE GSQYDAKSDM YSLGVILLEL FQPFGTEMER ATVLTGVRTG 540

RIPESLSKRC PVQAKYIQLL TGRNVSQRPS ALQLLQSELF QTTGNVNLTL QMKIIEQEKE 600

IEELKKQLSL LSQDRGLKR 619

Nucleotide Sequence
(FASTA)

ATGCTGGGGG GCAGCTCCGT GGACGGCGAG CGCGACACGG ACGACGACGC GGCGGGGGCG 60

GTGGCCGCGC CTCCTGCCAT CGACTTCCCC GCAGAGGTGT CGGACCCCAA GTATGATGAG 120

TCCGATGTCC CCGCAGAGCT CCAAGTGTTA AAAGAGCCCC TACAGCAGCC CACGTTCCCT 180

TTCCTGGTGG CAAACCAGCT GCTGCTCGTC TCCTTACTGG AACACTTGAG CCATGTGCAC 240

GAGCCAAACC CGCTCCACTC CAAACAGGTG TTTAAATTAC TGTGCCAGAC TTTTATCAAG 300

ATGGGGCTGC TCTCTTCCTT TACCTGCAGT GATGAGTTTA GCTCTCTGAG ACTCCACCAC 360

AACAGAGCCA TCACTCATTT AATGAGGTCT GCCAAAGAGA GAGTCCGTCA GGATCCTTGT 420

CAAGATAATT CTTACATGCA GAAAATCAGA TCCAGAGAGA TAGCCTTCGA AGCACAAACG 480

TCACGCTACT TAAATGAATT TGAAGAGCTT GCCATCTTAG GGAAAGGAGG ATATGGAAGA 540

GTTTACAAGG TCCGGAACAA ATTAGATGGT CAGCATTATG CAATTAAGAA AATCCTGATT 600

AAGAGCGCAA CTAAAACAGA TTGTATGAAG GTGCTACGGG AAGTGAAGGT TCTGGCAGGT 660

CTCCAGCATC CCAATATTGT TGGCTACCAC ACTGCGTGGA TAGAACATGT TCATGTGGTT 720

CAGCCACAAG ACAGAGTTCC GATTCAACTG CCCTCTCTCG AAGTGCTGTC GGAGCAGGAA 780

GGGGACAGAG ACCAAGGTGG TGTTAAAGAT AATGAAAGCA GTTCGTCCAT TGTCTTTGCT 840

GAACTCACCC CAGAAAAAGA AAAACCTTTT GGGGAGTCTG AGGTTAAAAA TGAGAATAAC 900

AACCTGGTGA GCTACACGGC CAACTTAGTG GTCAGGAACA GCAGTGAAAG TGAATCGTCC 960

ATTGAGCTCC AAGAAGACGG CTTGACTGAT TTGTCCGTCA GACCAGTTGT CAGGCATCAG 1020

CTGCCGCTGG GGCATAGCTC GGAATTGGAA GGGAATTTTA CATCCACGGA TGAGTCTTCT 1080

GAAGGCAACT TGAACCTGCT GGGGCAGACG GAGGTTCGGT ACCACCTGAT GTTGCACATC 1140

CAGATGCAGC TGTGTGAGCT CTCCCTGTGG GACTGGATAA CTGAGAGGAA CAAGCGGAGC 1200

CGGGAGTATG TGGACGAAGC TGCTTGTCCC TATGTTATGG CCAGTGTTGC AACAAAAATT 1260

TTTCAAGAAT TGGTGGAAGG TGTCTTTTAC ATACATAACA TGGGCATTGT CCACAGAGAT 1320

CTGAAGCCTA GAAATATTTT TCTTCATGGC CCTGATCAGC AAGTAAAAAT AGGAGACTTT 1380

GGTCTGGCCT GTGCAGACAT CATCCAGAAT GCAGACTGGA CCAACAGAAA TGGGAAAGGA 1440

ACACGGACAC ACACATCCAG AGTGGGGACT TGTCTCTACG CATCACCGGA ACAGCTGGAG 1500

GGATCCCAGT ACGATGCCAA GTCAGATATG TATAGCTTGG GTGTGATCCT GCTCGAGCTC 1560

TTTCAGCCAT TCGGGACAGA AATGGAGAGG GCAACAGTCT TAACAGGCGT AAGGACTGGT 1620

CGGATACCCG AATCCCTCAG TAAAAGGTGT CCGGTGCAAG CCAAGTATAT CCAGCTCCTA 1680

ACCGGGAGGA ATGTGTCACA GAGACCATCT GCCCTTCAGC TGCTGCAGAG TGAGCTTTTT 1740

CAAACAACTG GAAATGTTAA TCTCACATTG CAGATGAAGA TAATAGAACA AGAGAAGGAA 1800

ATTGAAGAAC TAAAGAAGCA ACTAAGCCTC CTTTCTCAGG ACAGAGGGCT GAAGAGATGA 1860

Domain Profile

S: 1     feeikvlGkGgfgvVlkaknkldkkeyaikriklnkakke.lekverevkaLaklehpni  59

         fee+++lGkGg+g+V+k++nkld+++yaik+i +++a+k+ ++kv+revk+La l+hpni

Q: 167   FEELAILGKGGYGRVYKVRNKLDGQHYAIKKILIKSATKTdCMKVLREVKVLAGLQHPNI  226

         899*********************************************************

S: 60    vrYfaawleekeesl...............................tdsseveaeaelee  88

         v Y++aw+e+ +  +                               ++ss v+ae ++e+

Q: 227   VGYHTAWIEHVHVVQpqdrvpiqlpslevlseqegdrdqggvkdneSSSSIVFAELTPEK  286

         ************999*****************************9656999*********

S: 89    sesseesdtk..................................................  98

         ++ + es++k

Q: 287   EKPFGESEVKnennnlvsytanlvvrnssesessielqedgltdlsvrpvvrhqlplghs  346

         ********999*************************************************

S: 99    ..............................llyiqmelceketLkdwiderk......ll  122

                                       +l+iqm+lce  +L+dwi+er+      ++

Q: 347   selegnftstdessegnlnllgqtevryhlMLHIQMQLCE-LSLWDWITERNkrsreyVD  405

         ****************************************.*********9999999999

S: 123   esrselvm.....rlfkqllegleylHskgliHrdLkpsniFld.sddqvKigDFgLata  176

         e+++ +vm     ++f++l+eg+ y+H++g++HrdLkp+niFl+  d+qvKigDFgLa+a

Q: 406   EAACPYVMasvatKIFQELVEGVFYIHNMGIVHRDLKPRNIFLHgPDQQVKIGDFGLACA  465

         99999999************************************99**************

S: 177   laealkedvkqdaqskeakhtgqvgtklymsPeqleksqYnkkvDifsLGlilfeLlypf  236

         ++  +++d+++++ +++++ht++vgt+ly+sPeqle+sqY++k+D++sLG+il+eL++pf

Q: 466   DII-QNADWTNRNGKGTRTHTSRVGTCLYASPEQLEGSQYDAKSDMYSLGVILLELFQPF  524

         655.5889****************************************************

S: 237   stemervetltelrdgkipedfddkvpkekkllqkllsrdpkeRpsasellksell  292

          temer+++lt +r+g+ipe++++++p+++k++q l+ r+ ++Rpsa +ll+sel+

Q: 525   GTEMERATVLTGVRTGRIPESLSKRCPVQAKYIQLLTGRNVSQRPSALQLLQSELF  580

         *****************************************************986

Domain Sequence
(FASTA)

FEELAILGKG GYGRVYKVRN KLDGQHYAIK KILIKSATKT DCMKVLREVK VLAGLQHPNI 60

VGYHTAWIEH VHVVQPQDRV PIQLPSLEVL SEQEGDRDQG GVKDNESSSS IVFAELTPEK 120

EKPFGESEVK NENNNLVSYT ANLVVRNSSE SESSIELQED GLTDLSVRPV VRHQLPLGHS 180

SELEGNFTST DESSEGNLNL LGQTEVRYHL MLHIQMQLCE LSLWDWITER NKRSREYVDE 240

AACPYVMASV ATKIFQELVE GVFYIHNMGI VHRDLKPRNI FLHGPDQQVK IGDFGLACAD 300

IIQNADWTNR NGKGTRTHTS RVGTCLYASP EQLEGSQYDA KSDMYSLGVI LLELFQPFGT 360

EMERATVLTG VRTGRIPESL SKRCPVQAKY IQLLTGRNVS QRPSALQLLQ SELF 414

Keyword

ATP-binding; Complete proteome; Cytoplasm; Disulfide bond; Kinase; Nucleotide-binding; Phosphoprotein; Protein synthesis inhibitor; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xiphophorus maculatus"; ?>Schizosaccharomyces pombe"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005524	; F:ATP binding
GO:0004694	; F:eukaryotic translation initiation factor 2alpha kinase activity
GO:0020037	; F:heme binding
GO:0008285	; P:negative regulation of cell proliferation
GO:0046986	; P:negative regulation of hemoglobin biosynthetic process
GO:0046777	; P:protein autophosphorylation
GO:0046501	; P:protoporphyrinogen IX metabolic process
GO:0010999	; P:regulation of eIF2 alpha phosphorylation by heme
GO:0009605	; P:response to external stimulus
GO:0006950	; P:response to stress

KEGG

mmu:15467

;

InterPros

IPR015516	; Haem-reg_EIF2A_Kinase.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00069

; Pkinase; 2.

SMARTs

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013