Q9BQI3 (E2AK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	EIF2AK1
Synonyms:	HRI, KIAA1369
ORF Names:	PRO1362

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	630 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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 By similarity.
Subunit structure	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. Forms oligomers. Has been reported as a non-covalently bound 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.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed predominantly in erythroid cells. At much lower levels, expressed in hepatocytes (at protein level). Ref.16
Post-translational modification	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 By similarity.
Miscellaneous	Can bind 1 molecules of heme per polypeptide chain By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. Contains 2 HRM (heme regulatory motif) repeats. Contains 1 protein kinase domain.
Sequence caution	The sequence AAF70289.1 differs from that shown. Reason: Frameshift at positions 24, 26 and 33. The sequence AAF71057.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA92607.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Protein synthesis inhibitor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of hemoglobin biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translational initiation by iron Non-traceable author statement Ref.14. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protoporphyrinogen IX metabolic process Inferred from electronic annotation. Source: Compara regulation of eIF2 alpha phosphorylation by heme Inferred from electronic annotation. Source: Compara response to external stimulus Inferred from expression pattern Ref.14. Source: UniProtKB response to stress Inferred from expression pattern Ref.14. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW eukaryotic translation initiation factor 2alpha kinase activity Inferred from direct assay Ref.14. Source: UniProtKB heme binding Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BQI3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9BQI3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     244-244: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 630	630	Eukaryotic translation initiation factor 2-alpha kinase 1		PRO_0000085941
Regions
	Domain	167 – 583	417	Protein kinase
	Repeat	410 – 415	6	HRM 1
	Repeat	552 – 557	6	HRM 2
	Nucleotide binding	173 – 181	9	ATP By similarity
Sites
	Active site	442	1	Proton acceptor By similarity
	Binding site	196	1	ATP By similarity
	Site	80	1	Heme-binding By similarity
Amino acid modifications
	Modified residue	486	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	488	1	Phosphothreonine; by autocatalysis By similarity
Natural variations
	Alternative sequence	244	1	Missing in isoform 2.		VSP_007589
	Natural variant	117	1	R → T. Ref.18 Corresponds to variant rs34889754 [ dbSNP | Ensembl ].		VAR_040466
	Natural variant	132	1	K → T. Ref.18 Corresponds to variant rs34851195 [ dbSNP | Ensembl ].		VAR_040467
	Natural variant	134	1	R → K. Ref.18 Corresponds to variant rs55744865 [ dbSNP | Ensembl ].		VAR_040468
	Natural variant	139	1	P → S. Ref.18 Corresponds to variant rs55963745 [ dbSNP | Ensembl ].		VAR_040469
	Natural variant	145	1	R → H. Ref.18 Corresponds to variant rs55971369 [ dbSNP | Ensembl ].		VAR_040470
	Natural variant	202	1	G → S in a lung adenocarcinoma sample; somatic mutation. Ref.18		VAR_040471
	Natural variant	292	1	F → L. Ref.18 Corresponds to variant rs55982710 [ dbSNP | Ensembl ].		VAR_040472
	Natural variant	319	1	L → H. Ref.18 Corresponds to variant rs34909691 [ dbSNP | Ensembl ].		VAR_040473
	Natural variant	558	1	K → R. Ref.8 Ref.13 Ref.18 Corresponds to variant rs2640 [ dbSNP | Ensembl ].		VAR_015732
Experimental info
	Sequence conflict	2	1	Q → L in AAF18391. Ref.3
	Sequence conflict	4	1	G → D in BAF83016. Ref.8
	Sequence conflict	24 – 32	9	PPAIDFPAE → RRHRLSRR in AAF70289. Ref.1
	Sequence conflict	137	1	Q → R in AAF70289. Ref.1
	Sequence conflict	149	1	I → T in BAF83016. Ref.8
	Sequence conflict	171	1	A → V in AAF18391. Ref.3
	Sequence conflict	206	1	T → P in AAF66736. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 20, 2003. Version 2. Checksum: D63021651806620B	FASTA	630	71,106
	10 20 30 40 50 60 MQGGNSGVRK REEEGDGAGA VAAPPAIDFP AEGPDPEYDE SDVPAEIQVL KEPLQQPTFP 70 80 90 100 110 120 FAVANQLLLV SLLEHLSHVH EPNPLRSRQV FKLLCQTFIK MGLLSSFTCS DEFSSLRLHH 130 140 150 160 170 180 NRAITHLMRS AKERVRQDPC EDISRIQKIR SREVALEAQT SRYLNEFEEL AILGKGGYGR 190 200 210 220 230 240 VYKVRNKLDG QYYAIKKILI KGATKTVCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVI 250 260 270 280 290 300 QPRADRAAIE LPSLEVLSDQ EEDREQCGVK NDESSSSSII FAEPTPEKEK RFGESDTENQ 310 320 330 340 350 360 NNKSVKYTTN LVIRESGELE STLELQENGL AGLSASSIVE QQLPLRRNSH LEESFTSTEE 370 380 390 400 410 420 SSEENVNFLG QTEAQYHLML HIQMQLCELS LWDWIVERNK RGREYVDESA CPYVMANVAT 430 440 450 460 470 480 KIFQELVEGV FYIHNMGIVH RDLKPRNIFL HGPDQQVKIG DFGLACTDIL QKNTDWTNRN 490 500 510 520 530 540 GKRTPTHTSR VGTCLYASPE QLEGSEYDAK SDMYSLGVVL LELFQPFGTE MERAEVLTGL 550 560 570 580 590 600 RTGQLPESLR KRCPVQAKYI QHLTRRNSSQ RPSAIQLLQS ELFQNSGNVN LTLQMKIIEQ 610 620 630 EKEIAELKKQ LNLLSQDKGV RDDGKDGGVG
	Isoform 2 [UniParc]. Checksum: B90159795D580809	FASTA	629	71,035
	10 20 30 40 50 60 MQGGNSGVRK REEEGDGAGA VAAPPAIDFP AEGPDPEYDE SDVPAEIQVL KEPLQQPTFP 70 80 90 100 110 120 FAVANQLLLV SLLEHLSHVH EPNPLRSRQV FKLLCQTFIK MGLLSSFTCS DEFSSLRLHH 130 140 150 160 170 180 NRAITHLMRS AKERVRQDPC EDISRIQKIR SREVALEAQT SRYLNEFEEL AILGKGGYGR 190 200 210 220 230 240 VYKVRNKLDG QYYAIKKILI KGATKTVCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVI 250 260 270 280 290 300 QPRDRAAIEL PSLEVLSDQE EDREQCGVKN DESSSSSIIF AEPTPEKEKR FGESDTENQN 310 320 330 340 350 360 NKSVKYTTNL VIRESGELES TLELQENGLA GLSASSIVEQ QLPLRRNSHL EESFTSTEES 370 380 390 400 410 420 SEENVNFLGQ TEAQYHLMLH IQMQLCELSL WDWIVERNKR GREYVDESAC PYVMANVATK 430 440 450 460 470 480 IFQELVEGVF YIHNMGIVHR DLKPRNIFLH GPDQQVKIGD FGLACTDILQ KNTDWTNRNG 490 500 510 520 530 540 KRTPTHTSRV GTCLYASPEQ LEGSEYDAKS DMYSLGVVLL ELFQPFGTEM ERAEVLTGLR 550 560 570 580 590 600 TGQLPESLRK RCPVQAKYIQ HLTRRNSSQR PSAIQLLQSE LFQNSGNVNL TLQMKIIEQE 610 620 KEIAELKKQL NLLSQDKGVR DDGKDGGVG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of hHRI, human heme-regulated eukaryotic initiation factor 2alpha kinase: down-regulated in epithelial ovarian cancers." Hwang S.-Y., Kim M.-K., Kim J.-C. Mol. Cells 10:584-591(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Hair follicle dermal papilla.
[2]	"Cloning and sequencing of a novel human cDNA homologous to rat hemin-sensitive initiation factor 2a kinase mRNA." Tu Q., Yu L., Hu P.R., Fu Q., Cui Y.Y., Zhao S.Y. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Cloning of the human heme-regulated eukaryotic initiation factor 2-alpha kinase from TNF-alpha stimulated dermal microvascular endothelial cells." Cannon G., Naik S.M., Boss J.M., Caughman S.W. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Skin.
[4]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hypothalamus.
[6]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala.
[7]	"Molecular cloning and sequencing of the human heme-regulated eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase from bone marrow culture." Omasa T., Chen Y.-G., Mantalaris A., Tsai Y.C., Wu J.H. DNA Seq. 13:133-137(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Bone marrow.
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-558. Tissue: Placenta and Tongue.
[9]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala.
[10]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"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] (ISOFORM 1). Tissue: Ovary.
[13]	"Functional prediction of the coding sequences of 121 new genes deduced by analysis of cDNA clones from human fetal liver." Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J., Liu M., He F. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 450-630, VARIANT ARG-558. Tissue: Fetal liver.
[14]	"Hsp90 regulates p50(cdc37) function during the biogenesis of the active conformation of the heme-regulated eIF2 alpha kinase." Shao J., Grammatikakis N., Scroggins B.T., Uma S., Huang W., Chen J.-J., Hartson S.D., Matts R.L. J. Biol. Chem. 276:206-214(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDC37 AND THE HSP90 COMPLEX.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[16]	"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: TISSUE SPECIFICITY.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-117; THR-132; LYS-134; SER-139; HIS-145; SER-202; LEU-292; HIS-319 AND ARG-558.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF255050 mRNA. Translation: AAF70289.1. Frameshift. AF100784 mRNA. Translation: AAP97223.1. AF181071 mRNA. Translation: AAF18391.1. AB037790 mRNA. Translation: BAA92607.1. Different initiation. AF183414 mRNA. Translation: AAG09683.1. AL136563 mRNA. Translation: CAB66498.1. AF147094 mRNA. Translation: AAF66736.1. AK075192 mRNA. Translation: BAC11461.1. AK290327 mRNA. Translation: BAF83016.1. AL834494 mRNA. Translation: CAD39152.1. CH236963 Genomic DNA. Translation: EAL23714.1. CH878731 Genomic DNA. Translation: EAW55049.1. BC006524 mRNA. Translation: AAH06524.1. AF116634 mRNA. Translation: AAF71057.1. Different initiation.
IPI	IPI00328149. IPI00328150.
RefSeq	NP_001127807.1. NM_001134335.1. NP_055228.2. NM_014413.3.
UniGene	Hs.520205.
3D structure databases
ProteinModelPortal	Q9BQI3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BQI3. 4 interactions.
STRING	9606.ENSP00000199389.
PTM databases
PhosphoSite	Q9BQI3.
Polymorphism databases
DMDM	32172458.
Proteomic databases
PaxDb	Q9BQI3.
PRIDE	Q9BQI3.
Protocols and materials databases
DNASU	27102.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000199389; ENSP00000199389; ENSG00000086232.
GeneID	27102.
KEGG	hsa:27102.
UCSC	uc003spp.3. human. uc003spq.3. human.
Organism-specific databases
CTD	27102.
GeneCards	GC07M006061.
H-InvDB	HIX0003741.
HGNC	HGNC:24921. EIF2AK1.
HPA	CAB022082. HPA016496.
neXtProt	NX_Q9BQI3.
PharmGKB	PA134919097.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG051429.
InParanoid	Q9BQI3.
KO	K16194.
OrthoDB	EOG43FGWK.
PhylomeDB	Q9BQI3.
Gene expression databases
ArrayExpress	Q9BQI3.
Bgee	Q9BQI3.
CleanEx	HS_EIF2AK1.
Genevestigator	Q9BQI3.
GermOnline	ENSG00000086232. Homo sapiens.
Family and domain databases
InterPro	IPR015516. Haem-reg_EIF2A_Kinase. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
PANTHER	PTHR11042:SF16. PTHR11042:SF16. 1 hit.
Pfam	PF00069. Pkinase. 2 hits. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9BQI3.
ChEMBL	CHEMBL6029.
ChiTaRS	EIF2AK1. human.
GenomeRNAi	27102.
NextBio	49763.

Entry information

Entry name

E2AK1_HUMAN

Accession

Primary (citable) accession number: Q9BQI3
Secondary accession number(s): A8K2R2 , Q549K6, Q8NBW3, Q9HC02, Q9NYE0, Q9P0V6, Q9P1J5, Q9P2H8, Q9UHG4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2001
Last sequence update:	June 20, 2003
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.