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Q9BQI3 (E2AK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length630 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Protein synthesis inhibitor
Serine/threonine-protein kinase
Transferase
   PTMDisulfide bond
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

regulation of eIF2 alpha phosphorylation by heme

Inferred from electronic annotation. Source: Ensembl

response to external stimulus

Inferred from expression pattern Ref.14. Source: UniProtKB

response to stress

Inferred from expression pattern Ref.14. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 630630Eukaryotic translation initiation factor 2-alpha kinase 1
PRO_0000085941

Regions

Domain167 – 583417Protein kinase
Repeat410 – 4156HRM 1
Repeat552 – 5576HRM 2
Nucleotide binding173 – 1819ATP By similarity

Sites

Active site4421Proton acceptor By similarity
Binding site1961ATP By similarity
Site801Heme-binding By similarity

Amino acid modifications

Modified residue4861Phosphothreonine; by autocatalysis By similarity
Modified residue4881Phosphothreonine; by autocatalysis By similarity

Natural variations

Alternative sequence2441Missing in isoform 2.
VSP_007589
Natural variant1171R → T. Ref.18
Corresponds to variant rs34889754 [ dbSNP | Ensembl ].
VAR_040466
Natural variant1321K → T. Ref.18
Corresponds to variant rs34851195 [ dbSNP | Ensembl ].
VAR_040467
Natural variant1341R → K. Ref.18
Corresponds to variant rs55744865 [ dbSNP | Ensembl ].
VAR_040468
Natural variant1391P → S. Ref.18
Corresponds to variant rs55963745 [ dbSNP | Ensembl ].
VAR_040469
Natural variant1451R → H. Ref.18
Corresponds to variant rs55971369 [ dbSNP | Ensembl ].
VAR_040470
Natural variant2021G → S in a lung adenocarcinoma sample; somatic mutation. Ref.18
VAR_040471
Natural variant2921F → L. Ref.18
Corresponds to variant rs55982710 [ dbSNP | Ensembl ].
VAR_040472
Natural variant3191L → H. Ref.18
Corresponds to variant rs34909691 [ dbSNP | Ensembl ].
VAR_040473
Natural variant5581K → R. Ref.8 Ref.13 Ref.18
Corresponds to variant rs2640 [ dbSNP | Ensembl ].
VAR_015732

Experimental info

Sequence conflict21Q → L in AAF18391. Ref.3
Sequence conflict41G → D in BAF83016. Ref.8
Sequence conflict24 – 329PPAIDFPAE → RRHRLSRR in AAF70289. Ref.1
Sequence conflict1371Q → R in AAF70289. Ref.1
Sequence conflict1491I → T in BAF83016. Ref.8
Sequence conflict1711A → V in AAF18391. Ref.3
Sequence conflict2061T → P in AAF66736. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 20, 2003. Version 2.
Checksum: D63021651806620B

FASTA63071,106
        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 

« Hide

Isoform 2 [UniParc].

Checksum: B90159795D580809
Show »

FASTA62971,035

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001127807.1. NM_001134335.1.
NP_055228.2. NM_014413.3.
UniGeneHs.520205.

3D structure databases

ProteinModelPortalQ9BQI3.
SMRQ9BQI3. Positions 162-618.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118002. 5 interactions.
IntActQ9BQI3. 4 interactions.
MINTMINT-4715350.
STRING9606.ENSP00000199389.

Chemistry

BindingDBQ9BQI3.
ChEMBLCHEMBL6029.
GuidetoPHARMACOLOGY2015.

PTM databases

PhosphoSiteQ9BQI3.

Polymorphism databases

DMDM32172458.

Proteomic databases

PaxDbQ9BQI3.
PRIDEQ9BQI3.

Protocols and materials databases

DNASU27102.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000199389; ENSP00000199389; ENSG00000086232. [Q9BQI3-1]
GeneID27102.
KEGGhsa:27102.
UCSCuc003spp.3. human. [Q9BQI3-1]
uc003spq.3. human. [Q9BQI3-2]

Organism-specific databases

CTD27102.
GeneCardsGC07M006061.
H-InvDBHIX0003741.
HGNCHGNC:24921. EIF2AK1.
HPACAB022082.
HPA016496.
neXtProtNX_Q9BQI3.
PharmGKBPA134919097.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG051429.
InParanoidQ9BQI3.
KOK16194.
OrthoDBEOG70GMF6.
PhylomeDBQ9BQI3.
TreeFamTF329383.

Enzyme and pathway databases

SignaLinkQ9BQI3.

Gene expression databases

ArrayExpressQ9BQI3.
BgeeQ9BQI3.
CleanExHS_EIF2AK1.
GenevestigatorQ9BQI3.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 2 hits.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEIF2AK1. human.
GeneWikiEIF2AK1.
GenomeRNAi27102.
NextBio49763.
PROQ9BQI3.

Entry information

Entry nameE2AK1_HUMAN
AccessionPrimary (citable) accession number: Q9BQI3
Secondary accession number(s): A8K2R2 expand/collapse secondary AC list , 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: March 19, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

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